Dr Kamal Dua holds two doctoral degrees in Pharmaceutical Sciences and Immunology & Microbiology, MPharm (with a Major in Pharmaceutics), and BPharm. Dr Dua has also successfully completed and been awarded four professional diplomas in the areas of Clinical Research, Product Development, Drug Regulatory Affairs & Documentation and Intellectual Property Rights (IPR). Dr Dua’s professional experience spans over 13 years in academia and research across 3 nations and 2 continents. His experience has allowed him to develop and implement both traditional and flexible student centered, innovative and engaging teaching modes that include e-learning and blended learning.
Dr Dua’s achievements throughout his academic and professional career have been recognised by various awards and fellowships including the Faculty of Health Dean’s Academic Excellence Award for Faculty Engagement (2019), Excellence Award in Pharmacy (2018), Young Scientist Award (2011), International Association for Dental Research Southeast Asian Division (IADR SEA; 2015); Dentsply Student Clinician Program Award (2014); the Educational Workshop Fellowship/Travel award by the World Society for Pediatric Infectious Diseases – WSPID (2011 & 2013); and the Sri. K. Sri Harsha Memorial Gold Medal & Rank Certificate (2004). Dr Dua is currently a lecturer with the Graduate School of Health (Pharmacy), University of Technology Sydney. His responsibilities include coordinating the academic and research activities associated with Master of Good Manufacturing Practice (GMP) courses.
Dr Dua also leads the Drug Delivery node of the Centre for Inflammation, Centenary Institute/University of Technology Sydney.
Dr Dua’s research experience spans 12 years where he has acquired extensive knowledge on the application of the principles of pharmacy (primarily formulation and pharmaceutics) to biomedical sciences (immunology and microbiology). His knowledge has been derived from extensive graduate and post-graduate research and training. To date, his research has resulted in the publication of 90 peer-reviewed manuscripts in various reputed pharmacy and pharmacology journals His publications have more than 1600 citations, and have resulted in the presentation of his research findings at numerous (>100) national and international conferences.
Dr Dua’s experience also includes the supervision of undergraduates [BPharm (Hons.), BSc. in Pharmaceutical Chemistry, Bachelor of Dental Surgery, and postgraduate (MPharm)] students. In total Kamal has supervised 18 undergraduate and 9 postgraduate projects involving both national and international students. Evidence of the quality of his research is reflected in his award of the Young Scientist Award by the Association of Pharmacy Professionals (APP), India in 2011 in recognition of his research work in the field of Pharmacy.
Dr Dua is an active researcher and has established both national and international collaborations with various Universities. These include The Queen’s University of Belfast, UK; The University of Bath, UK; Ulster University, UK; Hacettepe University, Turkey; University Sao Paulo, Brazil; Western Sydney University, Australia; Queensland University of Technology, Australia; The University of Newcastle, Australia; The University of Tasmania, Hobart TAS; Perdana University, Malaysia; The University of the West Indies, St. Augustine, Trinidad & Tobago; National Institute of Pharmaceutical Education and Research (NIPER), India, Birla Institute of Technology & Science (BITS), India and Amity University, India.
In the past Dr Dua has been actively involved with Dr Michael John Rathbone, ex-Professor and Dean, School of Pharmacy, International Medical University (IMU), Malaysia on various pharmacy research projects. Presently, this ongoing relationship takes the form of an industrial linkage where Dr Dua is involved as a consultant on quality systems management and GMP matters for ULTI Pharmaceuticals, Dr Rathbones New Zealand based animal health drug delivery technology company. Dr Dua also holds a conjoint lecturer position at the School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, The University of Newcastle, NSW, Australia.
Can supervise: YES
“Dr Dua is focussed on understanding the immunological mechanisms of chronic inflammatory diseases and defining potential therapies to be formulated into effective drug delivery systems. He ensures that his research is effective in driving impactful change in approaches to immunology through an expanded understanding of pharmaceutical research.”
Dr Dua is a Node Leader of Drug Delivery Research in the Centre for Inflammation at Centenary Institute/University of Technology Sydney, where the targets identified from the research projects are pursued to develop novel formulations as the first step towards translation into clinics. Dr Dua’s responsibilities include the development of formulations & drug delivery projects.
Dr Dua is a pharmaceutical and formulation scientist who recognized that there was limited information linking knowledge of various biological (handling and utilising mouse models; in vitro & ex vivo cell culture; cellular and molecular) approaches to drug delivery. This observation encouraged him to pursue research studies in the field of immunology and microbiology to enhance his ability to bridge the gap between formulation sciences (drug delivery) and biological advances, specifically addressing how these disciplines can advance one another helping the community to live longer and healthier.
Dr Dua studied immunology under the supervision of Professor Phil Hansbro, Director, Centre for Inflammation at Centenary Institute/University of Technology Sydney, an internationally recognised research leader in the area of respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). Working with Professor Hansbro, Dr Dua has demonstrated that specific factors such as microRNAs and IL-13 are elevated in experimental models of COPD and asthma and that inhibition of these factors suppresses disease pathology as well as prevents influenza infection. These findings possess the potential of translating into new and effective treatments for such chronic diseases. As such, Dr Dua is actively involved with Professor Hansbro to formulate the novel targets identified through intensive research into new, effective and patient complaint drug delivery systems with maximal efficacy for chronic respiratory and other inflammatory disease conditions.
Dr Dua’s research has also influenced the field of drug delivery by sparking recognition of encapsulating potential therapeutic moieties (Expert Opin Drug Deliv 2020; Cancers 2020; J Drug Deliv Sci Tech 2019; Int J Biol Macromol 2019; J Photochem Photobiol B 2019; Pharm Nanotechnol 2018; Colloids Surf B Biointerfaces 2018; Drug Deliv Transl Res 2017) into vesicular drug delivery systems to target chronic inflammatory conditions. Dr.Dua’s overall skills and expertise in formulation development combined with his in-depth knowledge of immunology & biological sciences opens new avenues for his research to contribute and expand in the area of pharmaceutical research.
Dr Dua’s other research interests include:
- Solubility enhancement of poorly water-soluble drugs using solid dispersions, molecular inclusion complexes, co-precipitates and salt-forming techniques.
- Topical, ocular and advanced (nanotechnology, liposomes and proniosomes) drug delivery systems (in dosage forms such as ointments, gels and creams).
- Transdermal drug delivery
- Periodontal drug delivery.
- Use of natural/herbal compounds in oral and topical dosage forms using novel approaches and their pharmacological investigations.
Good Manufacturing Practice (GMP)
This book examines numerous nanoparticle-based drug systems such as nanocrystals, dendrimers, polymeric micelles, protein-based, carbon nanotube, and liposomes that can offer advantages over traditional drug delivery systems such as ...
This book illustrates the importance and significance of oxidative stress in the pathophysiology of various human diseases.
The book initially introduces the phenomenon of oxidative stress, basic chemical characteristics of the species involved and summarizes the cellular oxidant and anti-oxidant system and the cellular effects and metabolism of the oxidative stress. In addition, it reviews the current understanding of the potential impact of oxidative stress on telomere shortening, aging, and age-related diseases. It also examines the role of oxidative stress in chronic diseases, including cancer, diabetes, cardiovascular diseases, and neurodegenerative disorders.
Further, the book presents novel technologies for the detection of oxidative stress biomarkers using nanostructure biosensors, as well as in vitro and in vivo models to monitor oxidative stress.
Lastly, the book addresses the drug delivery carriers that can help in combating oxidative stress.
Dirar, AI, Adhikari-Devkota, A, Kunwar, RM, Paudel, KR, Belwal, T, Gupta, G, Chellappan, DK, Hansbro, PM, Dua, K & Devkota, HP 2021, 'Genus Blepharis (Acanthaceae): A review of ethnomedicinally used species, and their phytochemistry and pharmacological activities', Journal of Ethnopharmacology, vol. 265.View/Download from: Publisher's site
© 2020 Elsevier B.V. Ethnopharmacological relevance: Blepharis is an Afro-Asiatic genus belonging to the family Acanthaceae. It comprises about 126 species that occur in arid and semi-arid habitats. Some species of Blepharis are used in traditional medicines in different countries mainly for their anti-inflammatory, wound healing activities along with treatment of gastrointestinal disorders and bone fractures. Aim of the review: The present review aims to collate and analyze the available data and information on distribution, traditional uses, chemical constituents and pharmacological activities of Blepharis. Methods: Scientific information of genus Blepharis was retrieved from the online bibliographic databases such as MEDLINE/PubMed, SciFinder, Web of Science and Google Scholar and secondary resources including books and proceedings. Results: Seven species of Blepharis were found to be reported frequently as useful in folklore in African and Asian countries. B. maderaspatensis was found to be widely used in Indian traditional medicines whereas the B. ciliaris and B. edulis were common in folklore of Egypt, Jordan, and Arabia. Active phytochemicals of Blepharis are flavonoids from B. ciliaris, alkaloids from B. sindica, phenolic acid derivatives, and phytosterols, and derivatives of hydroxamic acids from B. edulis resulted in possessing diverse biological properties such as anti-microbial, anti-inflammatory, and anti-cancer. Conclusions: Various species of Blepharis were found to be used in traditional medicine systems in African and Asian countries. Few of these species were studied for their bioactive chemical constituents however the activity guided isolation studies are not performed. Similarly, detailed pharmacological studies in animal models to explore their mechanism of action are also not reported. Future studies should focus on these aspects related to the medicinally used species of Blepharis. The detailed and comprehensive comparative analysis presen...
Malaiyandi, J, Anandapadmanaban, G, Perumalsamy, H, Kilankajae, A, Chellappan, DK, Dua, K, Shanmugam, G & Balusamy, SR 2020, 'Plumbagin from two Plumbago species inhibits the growth of stomach and breast cancer cell lines (vol 146, 112147, 2020)', INDUSTRIAL CROPS AND PRODUCTS, vol. 149.View/Download from: Publisher's site
Aggarwal, T, Wadhwa, R, Gupta, R, Paudel, KR, Collet, T, Chellapan, DK, Gupta, G, Perumalsamy, H, Mehta, M, Satija, S, Hansbro, PM, Dua, K & Maurya, PK 2020, 'MicroRNAs as Biomarker for Breast Cancer.', Endocrine, metabolic & immune disorders drug targets.View/Download from: Publisher's site
Regardless of advances in detection and treatment, breast cancer is a major cause of women death and affecting about 1.5 million women all over the world. Since the last decade, genome wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute large family of non-coding RNAs which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus for more studies on the role of microRNAs in breast cancer.
Aljabali, AAA, Alzoubi, L, Hamzat, Y, Alqudah, A, Obeid, MA, Al Zoubi, MS, Ennab, RM, Alshaer, W, Albatayneh, K, Al‑Trad, B, Alqudah, DA, Chellappan, DK, Gupta, G, Tambuwala, MM, Kamal, D & Evans, DJ 2020, 'An potential MRI agent and an anticancer drug encapsulated within CPMV virus-like particles', Combinatorial Chemistry & High Throughput Screening, vol. 23.View/Download from: Publisher's site
Virus nanoparticles have been extensively studied over the past decades for theranostics applications. Viruses are well-characterized, naturally occurring nanoparticles that can be produced in high quantity with a high degree of similarity in both structure and composition.
The plant virus cowpea mosaic virus (CPMV) has been innovatively used as a nanoscaffold. Utilization of the
internal cavity of empty virus-like particles (VLPs) for the inclusion of therapeutics within the capsid has opened many opportunities in drug delivery and imaging applications.
The encapsidation of magnetic materials and anticancer drugs was achieved. CPMV denotes molecules attached to the external surface of CPMV and CPMV denotes molecules within the interior of the capsid.
Here, the generation of novel VLPs incorporating iron-platinum nanoparticles TCPMVFePt and cisplatin (Cis)
(TCPMVCis) is reported. TCPMVCis have a cytotoxic IC50 of TCPMVCis on both A549 and MDA-MB-231 cell lines of 1.8 μM
and 3.9 µM respectively after 72 hours of incubation. The TCPMVFePt were prepared as potential MRI contrast agents.
Cisplatin loaded VLP (TCPMVCis) is shown to enhance cisplatin cytotoxicity in cancer cell lines, and its potency increased 2.3-folds.
Aljabali, AAA, Bakshi, HA, Hakkim, FL, Haggag, YA, Al-Batanyeh, KM, Al Zoubi, MS, Al-Trad, B, Nasef, MM, Satija, S, Mehta, M, Pabreja, K, Mishra, V, Khan, M, Abobaker, S, Azzouz, IM, Dureja, H, Pabari, RM, Dardouri, AAK, Kesharwani, P, Gupta, G, Dhar Shukla, S, Prasher, P, Charbe, NB, Negi, P, Kapoor, DN, Chellappan, DK, Webba da Silva, M, Thompson, P, Dua, K, McCarron, P & Tambuwala, MM 2020, 'Albumin Nano-Encapsulation of Piceatannol Enhances Its Anticancer Potential in Colon Cancer Via Downregulation of Nuclear p65 and HIF-1α.', Cancers, vol. 12, no. 1.View/Download from: Publisher's site
Piceatannol (PIC) is known to have anticancer activity, which has been attributed to its ability to block the proliferation of cancer cells via suppression of the NF-kB signaling pathway. However, its effect on hypoxia-inducible factor (HIF) is not well known in cancer. In this study, PIC was loaded into bovine serum albumin (BSA) by desolvation method as PIC-BSA nanoparticles (NPs). These PIC-BSA nanoparticles were assessed for in vitro cytotoxicity, migration, invasion, and colony formation studies and levels of p65 and HIF-1α. Our results indicate that PIC-BSA NPs were more effective in downregulating the expression of nuclear p65 and HIF-1α in colon cancer cells as compared to free PIC. We also observed a significant reduction in inflammation induced by chemical colitis in mice by PIC-BSA NPs. Furthermore, a significant reduction in tumor size and number of colon tumors was also observed in the murine model of colitis-associated colorectal cancer, when treated with PIC-BSA NPs as compared to free PIC. The overall results indicate that PIC, when formulated as PIC-BSA NPs, enhances its therpautice potential. Our work could prompt further research in using natural anticancer agents as nanoparticels with possiable human clinical trails. This could lead to the development of a new line of safe and effective therapeutics for cancer patients.
Aljabali, AAA, Bakshi, HA, Satija, S, Metha, M, Prasher, P, Ennab, RM, Chellapan, DK, Gupta, G, Negi, P, Goyal, R, Sharma, A, Mishra, V, Dureja, H, Dua, K & Tambuwala, MM 2020, 'COVID-19: Underpinning Research for Detection, Therapeutics, and Vaccines Development.', Pharmaceutical nanotechnology.View/Download from: Publisher's site
BACKGROUND:The newly emerged coronavirus SARS-CoV-2 first reported in December 2019 has infected upwards of five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities. OBJECTIVES:Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process.To acceleratethe scientfic advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers. METHODS:In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords matches the content of this review. RESULTS:The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus oninnovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2and strengthen future control measures.
Altamish, M, Dahiya, R, Singh, AK, Mishra, A, Aljabali, AAA, Satija, S, Mehta, M, Dureja, H, Prasher, P, Negi, P, Kapoor, DN, Goyal, R, Tambuwala, MM, Chellappan, DK, Dua, K & Gupta, G 2020, 'Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome', CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, vol. 30, no. 3, pp. 245-252.View/Download from: Publisher's site
Altamish, M, Samuel, VP, Dahiya, R, Singh, Y, Deb, PK, Bakshi, HA, Tambuwala, MM, Chellappan, DK, Collet, T, Dua, K & Gupta, G 2020, 'Molecular signaling of G-protein-coupled receptor in chronic heart failure and associated complications.', Drug Development Research, vol. 81, no. 1, pp. 23-31.View/Download from: Publisher's site
The well-known condition of heart failure is a clinical syndrome that results when the myocardium's ability to pump enough blood to meet the body's metabolic needs is impaired. Most of the cardiac activity is maintained by adrenoceptors, are categorized into two main α and β and three distinct subtypes of β receptor: β1-, β2-, and β3-adrenoceptors. The β adrenoreceptor is the main regulatory macro proteins, predominantly available on heart and responsible for down regulatory cardiac signaling. Moreover, the pathological involvement of Angiotensin-converting enzyme 1 (ACE1)/angiotensin II (Ang II)/angiotensin II type 1 (AT1) axis and beneficial ACE2/Ang (1-7)/Mas receptor axis also shows protective role via Gi βγ, during heart failure these receptors get desensitized or internalized due to increase in the activity of G-protein-coupled receptor kinase 2 (GRK2) and GRK5, responsible for phosphorylation of G-protein-mediated down regulatory signaling. Here, we investigate the various clinical and preclinical data that exhibit the molecular mechanism of upset level of GRK change the cardiac activity during failing heart.
Amawi, H, Abu Deiab, GI, A Aljabali, AA, Dua, K & Tambuwala, MM 2020, 'COVID-19 pandemic: an overview of epidemiology, pathogenesis, diagnostics and potential vaccines and therapeutics.', Therapeutic delivery, vol. 11, no. 4, pp. 245-268.View/Download from: Publisher's site
At the time of writing this review, severe acute respiratory coronavirus syndrome-2 (SARS-CoV-2) has infected more than 2,355,853 patients and resulted in more than 164,656 deaths worldwide (as of 20 April 2020). This review highlights the preventive measures, available clinical therapies and the potential of vaccine development against SARS-CoV-2 by taking into consideration the strong genetic similarities of the 2003 epidemic SARS-CoV. Recent studies are investigating the repurposing of US FDA-approved drugs as there is no available vaccine yet with many attempts under clinical evaluation. Several antivirals, antimalarials and immunomodulators that have shown activity against SARS-CoV and Middle East coronavirus respiratory syndromes are being evaluated. In particular, hydroxychloroquine, remdesivir, favipiravir, arbidol, tocilizumab and bevacizumab have shown promising results. The main aim of this review is to provide an overview of this pandemic and where we currently stand.
Bakshi, HA, Zoubi, MSA, Hakkim, FL, Aljabali, AAA, Rabi, FA, Hafiz, AA, Al-Batanyeh, KM, Al-Trad, B, Ansari, P, Nasef, MM, Charbe, NB, Satija, S, Mehta, M, Mishra, V, Gupta, G, Abobaker, S, Negi, P, Azzouz, IM, Dardouri, AAK, Dureja, H, Prasher, P, Chellappan, DK, Dua, K, Webba da Silva, M, El Tanani, M, McCarron, PA & Tambuwala, MM 2020, 'Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage.', Nutrients, vol. 12, no. 6.View/Download from: Publisher's site
Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.
Balusamy, SR, Veerappan, K, Ranjan, A, Kim, Y-J, Chellappan, DK, Dua, K, Lee, J & Perumalsamy, H 2020, 'Phyllanthus emblica fruit extract attenuates lipid metabolism in 3T3-L1 adipocytes via activating apoptosis mediated cell death.', Phytomedicine : international journal of phytotherapy and phytopharmacology, vol. 66.View/Download from: Publisher's site
BACKGROUND:Phyllanthus emblica L. (Indian gooseberry) is widely used in the Ayurveda for thousands of years to treat health complications including disorders of the immune system, diabetes, and obesity. PURPOSE:For the first time, our study aims to demonstrate the molecular mechanisms of the fruit extract of Phyllanthus emblica (PEFE) involved in the promotion of fat cell apoptosis and alleviation of adipogenesis. METHODS:The active constituents from PEFE were identified using high performance liquid chromatography-mass spectrometry (HPLC-MS). We carried out the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the cytotoxic effects of PEFE using 3T3-L1 pre-adipocytes. The colonogenic assay was carried out to determine the inhibitory effect of 3T3-L1 adipocytes after PEFE treatment. In addition, inhibition of pancreatic lipase activity was performed and the lipolytic activity of PEFE and digallic acid was compared with the well-known standard drug orlistat. Besides, the molecular interaction and ligand optimization between digallic and adipogenesis/apoptosis markers were also carried out. Furthermore, to confirm fat cell apoptosis we have used several detection methods that includes Hoechst staining, PI staining, Oil staining and qPCR respectively. RESULTS:Digallic acid was identified as a major component in the PEFE. The IC50 values of digallic acid and PEFE were found to be 3.82 µg/ml and 21.85 µg/ml respectively. PEFE and digallic acid showed significant anti-lipolytic activity compared to the standard drug orlistat. In the mature adipocytes, PEFE significantly decreased triglyceride accumulation by downregulating adiponectin, PPARγ, cEBPα, and FABP4 respectively. We further analyzed the expression of apoptosis related genes upon PEFE treatment. Apoptotic process initiated through upregulation of BAX and downregulation of BCL2 resulting in an increased caspase-3 activity. In addition, we have also confirmed the apoptosis a...
Chan, Y, Ng, SW, Xin Tan, JZ, Gupta, G, Tambuwala, MM, Bakshi, HA, Dureja, H, Dua, K, Ishaq, M, Caruso, V & Chellappan, DK 2020, 'Emerging therapeutic potential of the iridoid molecule, asperuloside: A snapshot of its underlying molecular mechanisms.', Chemico-biological interactions, vol. 315.View/Download from: Publisher's site
Over the years, the attention of researchers in the field of modern drug discovery and development has become further intense on the identification of active compounds from plant sources and traditional remedies, as they exhibit higher therapeutic efficacies and improved toxicological profiles. Among the large diversity of plant extracts that have been discovered and explored for their potential therapeutic benefits, asperuloside, an iridoid glycoside, has been proven to provide promising effects as a therapeutic agent for several diseases. Although, this potent substance exists in several genera, it is primarily found in plants belonging to the genus Eucommia. Recent decades have seen a surge in the research on Asperuloside, making it one of the most studied natural products in the field of medicine and pharmacology. In this review, we have attempted to study the various reported mechanisms of asperuloside that form the basis of its wide spectrum of pharmacological activities.
Chellappan, DK, Yee, LW, Xuan, KY, Kunalan, K, Rou, LC, Jean, LS, Ying, LY, Wie, LX, Chellian, J, Mehta, M, Satija, S, Singh, SK, Gulati, M, Dureja, H, Dureja, H, Da Silva, MW, Tambuwala, MM, Gupta, G, Paudel, KR, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases.', Drug development research, vol. 81, no. 4, pp. 419-436.View/Download from: Publisher's site
Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.
Chin, LH, Hon, CM, Chellappan, DK, Chellian, J, Madheswaran, T, Zeeshan, F, Awasthi, R, Aljabali, AA, Tambuwala, MM, Dureja, H, Negi, P, Kapoor, DN, Goyal, R, Paudel, KR, Satija, S, Gupta, G, Hsu, A, Wark, P, Mehta, M, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Molecular mechanisms of action of naringenin in chronic airway diseases.', European journal of pharmacology, vol. 879.View/Download from: Publisher's site
Chronic airway inflammatory diseases are characterized by persistent proinflammatory responses in the respiratory tract. Although, several treatment strategies are currently available, lifelong therapy is necessary for most of these diseases. In recent years, phytophenols, namely, flavonoids, derived from fruits and vegetables have been gaining tremendous interest and have been extensively studied due to their low toxicological profile. Naringenin is a bioflavonoid abundantly found in citrus fruits. This substance has shown notable therapeutic potential in various diseases due to its promising diverse biological activities. In this review, we have attempted to review the published studies from the available literature, discussing the molecular level mechanisms of naringenin in different experimental models of airway inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis and cystic fibrosis. Current evidences have proposed that the anti-inflammatory properties of naringenin play a major role in ameliorating inflammatory disease states. In addition, naringenin also possesses several other biological properties. Despite the proposed mechanisms suggesting remarkable therapeutic benefits, the clinical use of naringenin is, however, hampered by its low solubility and bioavailability. Furthermore, this review also discusses on the studies that utilise nanocarriers as a drug delivery system to address the issue of poor solubility.
Gandhi, H, Rathore, C, Dua, K, Vihal, S, Tambuwala, MM & Negi, P 2020, 'Efficacy of resveratrol encapsulated microsponges delivered by pectin based matrix tablets in rats with acetic acid-induced ulcerative colitis.', Drug development and industrial pharmacy, vol. 46, no. 3, pp. 365-375.View/Download from: Publisher's site
Objectives: The objective of the present work to encapsulate the resveratrol (RES) inside the chitosan-based microsponges, employing the systematic optimization by 33 Box-Behnken design for the colonic targeting.Significance: Enhanced therapeutic efficacy of RES-loaded microsponges and matrix tablets, vis-a-vis pureRES for ulcerative colitis.Methods: RES-loaded microsponges were prepared employing the systematic optimization by 33 Box-Behnken design for the colonic targeting. The best-optimizedRES-loaded microsponge was compressed in the form of a tablet, employing pectin as a matrix-forming material. The encapsulation of RES inside microsponge was confirmed by XRD, DSC and FT-IR. Further, both RES-loaded microsponges and matrix tablets were evaluated for in vitro release kinetics and further evaluated for in vivo ulcerative colitis animal model.Results: Optimization experiments was obtained as the high value of r2 (particle size = 0.9999; %EE = 0.9652; %CDR = 0.9469) inferred excellent goodness of fit. SEM revealed nearly spherical and porous nature of RES-loaded microsponges. The in vitro release kinetic showed zero-order release for RES-loaded microsponges and Korsmeyer-Peppas model for matrix tablets. The pharmacodynamic studies, in ulcerative colitis rat model, indicated better therapeutic efficacy of drug-loaded microsponges and matrix tablets, vis-a-vis pure RES. Thus, the present study advocates the potential of RES based microsponges delivered by pectin based matrix tablet, in the treatment of various colonic disorders.Conclusion: The present study proved that RES-loaded microsponges and matrix tablets based on chitosan and pectin can be the ideal delivery system for colonic delivery of RES.
Gupta, G, Dahiya, R, Singh, Y, Mishra, A, Verma, A, Gothwal, SK, Aljabali, AAA, Dureja, H, Prasher, P, Negi, P, Kapoor, DN, Goyal, R, Tambuwala, MM, Chellappan, DK & Dua, K 2020, 'Monotherapy of RAAS blockers and mobilization of aldosterone: A mechanistic perspective study in kidney disease.', Chemico-biological interactions, vol. 317.View/Download from: Publisher's site
In patients with acute kidney injury progressively converting into chronic kidney disease (CKD), proteinuria and high blood pressure predict progression to end-stage renal disease (ESRD). Although, Renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and kidney disease through both direct and indirect mechanisms. RAAS blockers that act at the level of angiotensin or lower in the cascade can cause compensatory increases in the plasma renin and angiotensin II level. Here, in this review article, we are exploring the evidence-based on RAAS blockade action releases of aldosterone and hypothesizing the molecular mechanism for converting the acute kidney injury into chronic kidney disease to end-stage renal disease.
Gupta, G, Singh, Y, Chellappan, D & Dua, K 2020, 'Emerging dermatological symptoms in coronavirus pandemic', JOURNAL OF COSMETIC DERMATOLOGY, vol. 19, no. 9, pp. 2447-2448.View/Download from: Publisher's site
Gupta, G, Singh, Y, Tiwari, J, Raizaday, A, Alharbi, KS, Al-Abbasi, FA, Kazmi, I, Satija, S, Tambuwala, MM, Devkota, HP, Krishnan, A, Chellappan, DK & Dua, K 2020, 'Beta-catenin non-canonical pathway: A potential target for inflammatory and hyperproliferative state via expression of transglutaminase 2 in psoriatic skin keratinocyte', DERMATOLOGIC THERAPY.View/Download from: Publisher's site
Hardwick, J, Taylor, J, Mehta, M, Satija, S, Paudel, KR, Hansbro, PM, Chellappan, DK, Bebawy, M & Dua, K 2020, 'Targeting Cancer using Curcumin Encapsulated Vesicular Drug Delivery Systems.', Current pharmaceutical design.View/Download from: Publisher's site
Curcumin is a major curcuminoid present in turmeric. The compound is attributed with various therapeutic properties, which include, anti-oxidant, anti-inflammatory, anti-bacterial, anti-malarial, and neuroprotection. Due to its therapeutic potential, curcumin has been employed for centuries in treating different ailments. Curcumin has been investigated lately as a novel therapeutic agent in the treatment of cancer. However, the mechanisms by which curcumin exerts its cytotoxic effects on malignant cells are still not fully understood. One of the main limiting factors in the clinical use of curcumin is its poor bioavailability and rapid elimination. Advancements in drug delivery systems such as, nanoparticle based vesicular drug delivery platforms have improved several parameters, namely, drug bioavailability, solubility, stability, and controlled release properties. The use of curcumin-encapsulated niosomes to improve the physical and pharmacokinetic properties of curcumin is one such approach. This review provides an up-to-date summary on nanoparticle based vesicular drug carriers and their therapeutic applications. Specifically, we focus on niosomes as novel drug delivery formulations and their potential in improving the delivery of challenging small molecules, including curcumin. Overall, the applications of such carriers will provide a new direction for novel pharmaceutical drug delivery, as well as, biotechnology, nutraceutical, and functional food industries.
Jayanthi, M, Gokulanathan, A, Haribalan, P, Ashakiran, K, Dinesh Kumar, C, Dua, K, Girija, S & Sri Renukadevi, B 2020, 'Plumbagin from two Plumbago species inhibits the growth of stomach and breast cancer cell lines', Industrial Crops and Products, vol. 146.View/Download from: Publisher's site
© 2020 Elsevier B.V. Plumbagin is a potent natural molecule that is found in several plants, especially in the genus of Plumbago. For centuries, plants containing this substance have been used therapeutically for various ailments according to the Indian traditional system of medicine. The aims of this study were, firstly, to compare the effectiveness of two different extraction methods for the isolation of plumbagin and, secondly, to compare the anti-proliferative effects of plumbagin in both field grown and in vitro grown plants of Plumbago indica L. and Plumbago zeylanica L. Plumbagin was quantified from different parts, viz from the leaf, stem and root of both field and in vitro grown plants of Plumbago indica. Plumbagin was isolated using the serial maceration extraction method using methanol as solvent. Anti-proliferative activity of selected extracts was examined in both stomach cancer cell lines (AGS) and breast cancer cell lines (MDA-MB-231). Quantification of plumbagin was performed by reverse phase high performance liquid chromatography (HPLC). The leaves, stem and roots of the in vitro grown Plumbago indica yielded 70.98 mg g−1, 22.45 mg g−1and 342.15 mg g−1of content, respectively. This was higher when compared to the field grown parts (28.87 mg g−1, 11.54 mg g-1 and 2687 mg g−1). We have demonstrated that different extraction methods have varied yield of plumbagin. The isolated compound was then tested for its anti-proliferative activity. Also, we have confirmed apoptotic medicated cell death by nucleus staining to detect cell death by the treatment of different type of extract of both Plumbago indica L. and Plumbago zeylanica L.
Kaur, G, Singh, SK, Kumar, R, Kumar, B, Kumari, Y, Gulati, M, Pandey, NK, Gowthamarajan, K, Ghosh, D, Clarisse, A, Wadhwa, S, Mehta, M, Satija, S, Dua, K, Dureja, H, Gupta, S, Singh, PK, Kapoor, B, Chitranshi, N, Kumar, A & Porwal, O 2020, 'Development of modified apple polysaccharide capped silver nanoparticles loaded with mesalamine for effective treatment of ulcerative colitis', Journal of Drug Delivery Science and Technology, vol. 60.View/Download from: Publisher's site
© 2020 Elsevier B.V. The objective of study was to develop modified apple polysaccharide (MAP) based silver nanoparticles (AgNPs) loaded with mesalamine (MES) for effective treatment of ulcerative colitis in acetic acid induced rat model. AgNPs were prepared by reducing silver nitrate using MAP solution. The size and zeta potential of AgNPs was 89 ± 3 nm and −16.3 ± 1.54 mV and AgNPs loaded with MES (AgNPs-MES) was 101 ± 9 nm and −14.27 ± 2.16 mV. The dissolution study revealed about 54% drug release after 5 h indicating release of drug at the colonic site. The in vivo study was carried out on acetic acid induced ulcerative colitis rats and efficacy of treatment was assessed through evaluation of disease activity index and level of antioxidants as well as tumor necrosis factor-α after 7th and 14th day of induction of colitis. Histopathological evaluation of colonic tissue was also carried out. The results revealed that AgNPs-MES (high dose) provided better therapeutic efficacy for the treatment of UC as compared to its low dose, MES alone, MES-MAP, AgNPs alone and MAP alone. It was concluded that MAP based AgNPs loaded with MES were successfully formulated and found to be effective in treating ulcerative colitis.
Kou, J, Xin, TY, McCarron, P, Gupta, G, Dureja, H, Satija, S, Mehta, M, Bakshi, HA, Tambuwala, MM, Collet, T, Dua, K & Chellappan, DK 2020, 'Going beyond antibiotics: natural plant extracts as an emergent strategy to combat biofilm-associated infections', Journal of Environmental Pathology, Toxicology and Oncology, vol. 39, no. 2, pp. 125-136.View/Download from: Publisher's site
© 2020 by Begell House, Inc. Biofilms are a collective of multiple types of bacteria that develop on a variety of surfaces. Biofilm development results in heightened resistance to antibiotics. Quorum sensing plays an important role in biofilm development as it is one of the common communication mechanisms within cells, which balances and stabilizes the environment, when the amount of bacteria increases. Because of the important implications of the roles biofilms play in infectious diseases, it is crucial to investigate natural antibacterial agents that are able to regulate biofilm formation and development. Various studies have suggested that natural plant products have the potential to suppress bacterial growth and exhibit chemopre-ventive traits in the modulation of biofilm development. In this review, we discuss and collate potential antibiofilm drugs and biological molecules from natural sources, along with their underlying mechanisms of action. In addition, we also discuss the antibiofilm drugs that are currently under clinical trials and highlight their potential future uses.
Kumar, M, Nishad, DK, Kumar, A, Bhatnagar, A, Karwasra, R, Khanna, K, Keerthana, S, Sharma, D, Dua, K, Mudaliyar, V & Sharma, N 2020, 'Enhancement in brain uptake of vitamin D(3)nanoemulsion for treatment of cerebral ischemia: formulation, gamma scintigraphy and efficacy study in transient middle cerebral artery occlusion rat models', JOURNAL OF MICROENCAPSULATION.View/Download from: Publisher's site
Madan, JR, Ansari, IN, Dua, K & Awasthi, R 2020, 'Formulation and in vitro evaluation of casein nanoparticles as carrier for celecoxib', Advanced Pharmaceutical Bulletin, vol. 10, no. 3, pp. 408-417.View/Download from: Publisher's site
© 2020 The Author (s). This is an Open Access article distributed under the terms of the Creative Commons Attribution (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, as long as the original authors and source are cited. No permission is required from the authors or the publishers. Purpose: The objective of this work was to formulate casein (CAS) nanocarriers for the dissolution enhancement of poorly water soluble drug celecoxib (CLXB). Methods: The CLXB loaded CAS nanocarriers viz., nanoparticles, reassembled CAS micelles and nanocapsules were prepared using sodium caseinate (SOD-CAS) as a carrier to enhance the solubility of CLXB. The prepared formulations were characterized for particle size, polydispersity index, zeta potential, percentage entrapment efficiency, and surface morphology for the selection of best formulation. Fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction study was used to for the confirmation of encapsulation of CLXB. Further, in vitro drug dissolution, ex-vivo permeation studies on chicken ileum and stability studies were carried out. Results: The CLXB loaded casein nanoparticles (CNP) (batch A2) showed a particle size diameter 216.1 nm, polydispersity index 0.422 with percentage entrapment efficiency of 90.71% and zeta potential of -24.6 mV. Scanning electron microscopy of suspension confirmed globular shape of CNP. The in vitro release data of optimized batch followed non Fickian diffusion mechanism. The ex vivo permeation studies on chicken ileum of CLXB loaded CNP showed permeation through mucous membrane as compared to pure CLXB. The apparent permeability of best selected freeze dried CLXB loaded CNP (batch A2) was higher and gradually increased from 0.90 mg/cm2 after 10 min to a maximum of 1.95 mg/cm2 over the subsequent 90 min. A higher permeation was recorded at each time point than that of the pure CLXB. Conclusion: The study explored the po...
Madan, JR, Khobaragade, S, Dua, K & Awasthi, R 2020, 'Formulation, optimization, and in vitro evaluation of nanostructured lipid carriers for topical delivery of Apremilast', DERMATOLOGIC THERAPY.View/Download from: Publisher's site
Madan, JR, Patil, K, Awasthi, R & Dua, K 2020, 'Formulation and evaluation of solid self-microemulsifying drug delivery system for azilsartan medoxomil', International Journal of Polymeric Materials and Polymeric Biomaterials.View/Download from: Publisher's site
© 2019, © 2019 Taylor & Francis Group, LLC. This study aimed to develop solid self-microemulsifying drug delivery system (S-SMEDDS) for solubility enhancement of azilsartan medoxomil (AZL). Ternary phase diagrams were constructed using surfactant: co-surfactant at 1:0, 1:1, 1:2 and 2:1 ratios. Initially, the oils, surfactants and co-surfactants were screened. The drug–soya lecithin complexes were prepared and characterized for complexation percentage, complex solubility, and partition coefficient. The liquid SMEDDS were prepared and evaluated for thermodynamic stability, self-emulsification efficiency and time, viscosity, size and polydispersibility index, zeta potential, drug loading, and in vitro dissolution. Further, the solid SMEDDS were formulated and evaluated for morphological characterization, and thermal behavior. The solid SMEDDS were filled with hard gelatin capsule and accessed for in vitro drug release profile. S-SMEDDS containing Syloid® XDP 3150 had highest adsorption capacity. Self-emulsification time, drug loading and percentage transmittance were 25 ± 1.23 s, 99.20 ± 0.11% and 99.3 ± 0.1%, respectively. Particle size, polydispersibility index and zeta potential were 201.0 nm, 0.544 and -19.7 mV, respectively. S-SMEDDS had good flow property, spontaneous self-microemulsification property and improved in vitro dissolution profile of AZL when compared to pure AZL.
Malyla, V, Paudel, KR, Shukla, SD, Donovan, C, Wadhwa, R, Pickles, S, Chimankar, V, Sahu, P, Bielefeldt-Ohmann, H, Bebawy, M, Hansbro, PM & Dua, K 2020, 'Recent advances in experimental animal models of lung cancer', Future Medicinal Chemistry.View/Download from: Publisher's site
Mehta, M, Dhanjal, DS, Paudel, KR, Singh, B, Gupta, G, Rajeshkumar, S, Thangavelu, L, Tambuwala, MM, Bakshi, HA, Chellappan, DK, Pandey, P, Dureja, H, Charbe, NB, Singh, SK, Shukla, SD, Nammi, S, Aljabali, AA, Wich, PR, Hansbro, PM, Satija, S & Dua, K 2020, 'Cellular signalling pathways mediating the pathogenesis of chronic inflammatory respiratory diseases: an update', INFLAMMOPHARMACOLOGY, vol. 28, no. 4, pp. 795-817.View/Download from: Publisher's site
Mehta, M, Prasher, P, Sharma, M, Shastri, MD, Khurana, N, Vyas, M, Dureja, H, Gupta, G, Anand, K, Satija, S, Chellappan, DK & Dua, K 2020, 'Advanced drug delivery systems can assist in targeting coronavirus disease (COVID-19): A hypothesis', Medical Hypotheses, vol. 144, pp. 110254-110254.View/Download from: Publisher's site
Mehta, M, Satija, S, Paudel, KR, Liu, G, Chellappan, DK, Hansbro, PM & Dua, K 2020, 'Incipient need of targeting airway remodeling using advanced drug delivery in chronic respiratory diseases', FUTURE MEDICINAL CHEMISTRY, vol. 12, no. 10, pp. 873-875.View/Download from: Publisher's site
Mishra, V, Nayak, P, Singh, M, Tambuwala, MM, Aljabali, AA, Chellappan, DK & Dua, K 2020, 'Pharmaceutical aspects of green synthesized silver nanoparticles: A boon to cancer treatment.', Anti-cancer agents in medicinal chemistry.View/Download from: Publisher's site
BACKGROUND:Silver nanoparticles (AgNPs) are one of the most investigated nanostructures in recent years, which gives more challenging and promising qualities in different biomedical applications. The AgNPs synthesized by the green approach provide potential healthcare benefits over chemical approaches, including improvement of tissue restoration, drug delivery, diagnosis, environmentally friendly and a boon to cancer treatment. OBJECTIVE:In the current scenario, the development of safe and effective drug delivery systems is the utmost concern of formulation development scientists as well as clinicians. METHODS:Google, Web of Science, PubMed, portals have been searched for potentially relevant literature to get latest developments and updated information related to different aspects of green synthesized AgNPs along with their biomedical applications especially in the treatment of different types of cancers. RESULTS:The present review highlights the latest published research regarding the different green approaches for the synthesis of AgNPs, their characterization techniques as well as various biomedical applications, particularly in cancer treatment. In this context, environment friendly AgNPs are proving themselves as better candidates in terms of size, drug loading and release efficiency, targeting efficiency, minimal drug-associated side effects, pharmacokinetic profiling, and biocompatibility issues. CONCLUSION:With continuous efforts by multidisciplinary team approaches, nanotechnology-based AgNPs will shed new light on diagnostics and therapeutics in various disease treatments. However, the toxicity issues of AgNPs needs the greatest attention as unanticipated toxic effects must be ruled out for their diversified applications.
Ng, PQ, Ling, LSC, Chellian, J, Madheswaran, T, Panneerselvam, J, Kunnath, AP, Gupta, G, Satija, S, Mehta, M, Hansbro, PM, Collet, T, Dua, K & Chellappan, DK 2020, 'Applications of Nanocarriers as Drug Delivery Vehicles for Active Phytoconstituents.', Current pharmaceutical design.View/Download from: Publisher's site
Many plant-based bioactive compounds have been serving as the origin of drugs since long ago and many of them have been proven to have medicinal value against various chronic diseases, including, cancer, arthritis, hepatic diseases, type 2 diabetes and cardiovascular diseases. However, their clinical applications have been limited due to their poor water solubility, stability, low bioavailability and extensive transformation due to first-pass metabolism. The applications of nanocarriers have been proven to be able to improve the delivery of bioactive phytoconstituents, resulting in the enhancement of various pharmacokinetic properties and thereby, increase the therapeutic value of phytoconstituents. These biocompatible nanocarriers also exert low toxicity to healthy cells. This review focuses on the uses and applications of different types of nanocarriers to enhance the delivery of phytoconstituents for the treatment of various chronic diseases, along with comparisons related to bioavailability and therapeutic efficacy of nano phytoconstituents with native phytoconstituents.
Pandey, P, Satija, S, Wadhwa, R, Mehta, M, Purohit, D, Gupta, G, Prasher, P, Chellappan, DK, Awasthi, R, Dureja, H & Dua, K 2020, 'Emerging trends in nanomedicine for topical delivery in skin disorders: Current and translational approaches.', Dermatologic therapy, vol. 33, no. 3.View/Download from: Publisher's site
Pardhi, DM, Şen Karaman, D, Timonen, J, Wu, W, Zhang, Q, Satija, S, Mehta, M, Charbe, N, McCarron, PA, Tambuwala, MM, Bakshi, HA, Negi, P, Aljabali, AA, Dua, K, Chellappan, DK, Behera, A, Pathak, K, Watharkar, RB, Rautio, J & Rosenholm, JM 2020, 'Anti-bacterial activity of inorganic nanomaterials and their antimicrobial peptide conjugates against resistant and non-resistant pathogens.', International journal of pharmaceutics, vol. 586.View/Download from: Publisher's site
This review details the antimicrobial applications of inorganic nanomaterials of mostly metallic form, and the augmentation of activity by surface conjugation of peptide ligands. The review is subdivided into three main sections, of which the first describes the antimicrobial activity of inorganic nanomaterials against gram-positive, gram-negative and multidrug-resistant bacterial strains. The second section highlights the range of antimicrobial peptides and the drug resistance strategies employed by bacterial species to counter lethality. The final part discusses the role of antimicrobial peptide-decorated inorganic nanomaterials in the fight against bacterial strains that show resistance. General strategies for the preparation of antimicrobial peptides and their conjugation to nanomaterials are discussed, emphasizing the use of elemental and metallic oxide nanomaterials. Importantly, the permeation of antimicrobial peptides through the bacterial membrane is shown to aid the delivery of nanomaterials into bacterial cells. By judicious use of targeting ligands, the nanomaterial becomes able to differentiate between bacterial and mammalian cells and, thus, reduce side effects. Moreover, peptide conjugation to the surface of a nanomaterial will alter surface chemistry in ways that lead to reduction in toxicity and improvements in biocompatibility.
Paudel, KR, Wadhwa, R, Mehta, M, Chellappan, DK, Hansbro, PM & Dua, K 2020, 'Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro.', Toxicology in vitro : an international journal published in association with BIBRA, vol. 68.View/Download from: Publisher's site
Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.
Prasher, P, Sharma, M, Aljabali, AAA, Gupta, G, Negi, P, Kapoor, DN, Singh, I, Zacconi, FC, de Jesus Andreoli Pinto, T, da Silva, MW, Bakshi, HA, Chellappan, DK, Tambuwala, MM & Dua, K 2020, 'Hybrid molecules based on 1,3,5-triazine as potential therapeutics: A focused review', Drug Development Research.View/Download from: Publisher's site
© 2020 Wiley Periodicals, LLC. Majority of the representative drugs customarily interact with multiple targets manifesting unintended side effects. In addition, drug resistance and over expression of the cellular efflux-pumps render certain classes of drugs ineffective. With only a few innovative formulations in development, it is necessary to identify pharmacophores and novel strategies for creating new drugs. The conjugation of dissimilar pharmacophoric moieties to design hybrid molecules with an attractive therapeutic profile is an emerging paradigm in the contemporary drug development regime. The recent decade witnessed the remarkable biological potential of 1,3,5-triazine framework in the development of various chemotherapeutics. The appending of the 1,3,5-triazine nucleus to biologically relevant moieties has delivered exciting results. The present review focuses on 1,3,5-triazine based hybrid molecules in the development of pharmaceuticals.
Prasher, P, Sharma, M, Gupta, G, Chellappan, DK & Dua, K 2020, 'Are Medicinal Plants an Alternative Strategy to Combat COVID-19?', Alternative therapies in health and medicine.
No Abstract Available.
Prasher, P, Sharma, M, Mudila, H, Gupta, G, Sharma, AK, Kumar, D, Bakshi, HA, Negi, P, Kapoor, DN, Chellappan, DK, Tambuwala, MM & Dua, K 2020, 'Emerging trends in clinical implications of bio-conjugated silver nanoparticles in drug delivery', Colloids and Interface Science Communications, vol. 35.View/Download from: Publisher's site
© 2020 Elsevier B.V. From nanopharmaceutics to renewable energy, silver nanoparticles (AgNPs) present innumerable applications in the contemporary era. However, the associated toxicity to the biosystems limits their application. Effective utilization of AgNPs, therefore, requires their surface conjugation with biologically benevolent moieties that enhance the bio-acceptability of silver-based nanosystems, and supplementary functionalities for further extension of their unique applications. The clinical importance of AgNPs was established long ago, but their clinical utilization has been explored only recently with the phenomenon of bio-conjugation. The biomolecule-conjugated AgNPs present operable solutions for tedious clinical complications of the present era, such as multidrug resistance, designing of pharmaceuticals with improved bioavailability, superior drug delivery vehicles and in situ bio imaging of important metabolites that utilize the biomolecule-anchored surface engineered AgNPs. This review epigrammatically discusses some interesting clinical applications of surface conjugated AgNPs with biomolecules such as peptides, nucleic acids, amino acids and antibodies in the current nanopharmaceutical paradigm.
Prasher, P, Sharma, M, Zacconi, F, Gupta, G, Aljabali, AA, Mishra, V, Tambuwala, MM, Kapoor, DN, Negi, P, Andreoli Pinto, TDJ, Singh, I, Chellappan, DK & Dua, K 2020, 'Synthesis and anticancer properties of 'azole'based chemotherapeutics as emerging chemical moieties: A comprehensive review', Current Organic Chemistry, vol. 24.View/Download from: Publisher's site
Azole frameworks serve as privileged scaffolds in the contemporary drug design paradigm owing to their unique physicochemical profile that promotes the development of highly selective, physiological benevolent chemotherapeutics. Several azole nuclei function as bioisostere in medicinal chemistry and prompt the development of tailored therapeutics for targeting the desired biological entities. Besides, the azole scaffold forms an integral part in the advanced drug designing methodologies such as target template insitu drug synthesis, that assist in a rapid identification of the hit molecules form a diverse pool of leads; and direct biomolecule-drug conjugation, along with bioorthogonal strategies that ensure localization, and a superior target specificity of the directed therapeutic. Lastly, the structural diversity of azole framework and high yielding click synthetic methods provide a comprehensive Structure Activity Relationship analysis for design optimization of the potential drug molecules by fine-tuning the placement of different substituents critical for the activity. This review provides a comprehensive analysis of the synthesis and anticancer potential of azole based chemotherapeutics.
Ranpise, HA, Gujar, KN, Pawar, SC, Awasthi, R, Dua, K, Mathure, D & Madan, JR 2020, 'Formulation, optimization, and evaluation of ketoconazole loaded nanostructured lipid carrier gel for topical delivery', Drug Delivery Letters, vol. 10, no. 1, pp. 61-71.View/Download from: Publisher's site
© 2020 Bentham Science Publishers. Objective: Ketoconazole is used in the treatment of superficial and systemic fungal infections. It acts by blocking the synthesis of ergosterol, an essential component of the fungal cell membrane. The purpose of this work was to formulate ketoconazole loaded nanostructured lipid carriers formulation for skin targeting to minimize the adverse side effects and to prolong release. Methods: The ketoconazole loaded nanostructured lipid carriers were optimized using 32 factorial design to evaluate the effects of process and formulation variables. The nanostructured lipid carriers were prepared by melt-dispersion ultra-sonication method. The formulations were finally incorporated into polymeric gels of Carbopol 940 for convenient application. The gels were evaluated comparatively with commercially available formulations of ketoconazole with respect to ex vivo skin permeation and deposition study on human cadaver skin. Results: Nanostructured lipid carriers showed average particle size, zeta potential, and percentage entrapment in the range of 125.8 ± 1.8 to 295.0 ± 3.8 nm,-13.2 ± 1.1 to-30.9 ± 2.2 mV, and 69.47 ± 2.8 to 95.49 ± 4.5, respectively. Thermal studies revealed no drug-excipient incompatibility and amorphi-zation of ketoconazole. Ex vivo study of the gel exhibited prolonged drug release up to 12 h. In vitro drug deposition study showed that the gel formulation can avoid the systemic uptake, better accumulative uptake of the drug, and nonirritant to the skin compared to marketed formulation. Optimized formulation exhibited better antifungal activity when compared to ketoconazole loaded gel and marketed cream (Keto® cream). Histolopathology results indicated no toxic effect on the skin. Conclusions: These results indicate that developed nanostructured lipid-carriers gel formulation represents a promising carrier for topical delivery of ketoconazole, having controlled drug release, and potential of skin targeting.
Rathore, C, Rathbone, MJ, Chellappan, DK, Tambuwala, MM, Pinto, TDJA, Dureja, H, Hemrajani, C, Gupta, G, Dua, K & Negi, P 2020, 'Nanocarriers: more than tour de force for thymoquinone.', Expert opinion on drug delivery, vol. 17, no. 4, pp. 479-494.View/Download from: Publisher's site
Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.
Rathore, C, Upadhyay, N, Kaundal, R, Dwivedi, RP, Rahatekar, S, John, A, Dua, K, Tambuwala, MM, Jain, S, Chaudari, D & Negi, P 2020, 'Enhanced oral bioavailability and hepatoprotective activity of thymoquinone in the form of phospholipidic nano-constructs.', Expert opinion on drug delivery, vol. 17, no. 2, pp. 237-253.View/Download from: Publisher's site
Background: The poor biopharmaceutical properties of thymoquinone (TQ) obstruct its development as a hepatoprotective agent. To surmount the delivery challenges of TQ, phospholipid nanoconstructs (PNCs) were constructed.Method: PNCs were constructed employing microemulsification technique and systematic optimization by three-factor three level Box-Behnken design.Result: Optimized PNC composition exhibited nano size (<100 nm), spherical morphology, within acceptable range of polydispersity index (0.55), high drug entrapment efficiency (>90%), controlled drug release pattern, and neutral surface charge (zeta potential of -0.65 mV). After oral administration of a single dose of PNC, it showed a relative bioavailability of 386.03% vis-à-vis plain TQ suspension. Further, TQ-loaded PNC demonstrated significant enhanced hepato-protective effect vis-à-vis pure TQ suspension and silymarin, as evidenced by reduction in the ALP, ALT, AST, bilirubin, and albumin level and ratified by histopathological analysis.Conclusion: TQ-loaded PNCs can be efficient nano-platforms for the management of hepatic disorders and promising drug delivery systems to enhance oral bioavailability of this hydrophobic molecule.
Rawat, S, Gupta, G, Pathak, S, Singh, SK, Singh, H, Mishra, A, Gilhotra, R, Aljabali, AAA, Dureja, H, Tambuwala, MM, Chellappan, DK & Dua, K 2020, 'Current biological and pharmacological updates on wogonin.', EXCLI journal, vol. 19, pp. 635-640.
Raychaudhuri, R, Pandey, A, Hegde, A, Abdul Fayaz, SM, Chellappan, DK, Dua, K & Mutalik, S 2020, 'Factors affecting the morphology of some organic and inorganic nanostructures for drug delivery: Characterization, modifications and toxicological perspectives.', Expert opinion on drug delivery.View/Download from: Publisher's site
INTRODUCTION:In this review, we aim to highlight the impact of various processes and formulation variables influencing the characteristics of certain surfactant based nanoconstructs for drug delivery. AREAS COVERED:The review includes the discussion on processing parameters for the preparation of nanoconstructs, especially those made up of surfactants. Articles published in last 15 years (437) were reviewed, 381 articles were selected for data review and most appropriate articles (215) were included in article. Effect of variables such as surfactant concentration and type, membrane additives, temperature and pH-dependent transitions on morphology have been highlighted along with effect of shape on nanoparticle uptake by cells. Various characterization techniques explored for these nanostructure with respect to size, morphology, lamellarity, distribution etc., and a separate section on polymeric vesicles and the influence of block copolymers, type of block copolymer, control of block length, interaction of multiple block copolymers on the structure of polymersomes and chimeric nanostructures has been discussed. Finally, applications, modification, degradation and toxicological aspects of these drug delivery systems have been highlighted. EXPERT OPINION:Parameters influencing the morphology of micelles and vesicles can directly or indirectly affect the efficacy of small molecule cellular internalization as well as uptake in the case of biologicals. [Figure: see text].
Satija, S, Mehta, M, Sharma, M, Prasher, P, Gupta, G, Chellappan, DK & Dua, K 2020, 'Vesicular drug-delivery systems as theranostics in COVID-19.', Future medicinal chemistry.View/Download from: Publisher's site
Satija, S, Tambuwala, MM, Pabreja, K, Bakshi, HA, Chellappan, DK, Aljabali, AA, Nammi, S, Singh, TG, Dureja, H, Gupta, G, Dua, K, Mehta, M & Garg, M 2020, 'Development of a novel HPTLC fingerprint method for simultaneous estimation of berberine and rutin in medicinal plants and their pharmaceutical preparations followed by its application in antioxidant assay', Journal of Planar Chromatography - Modern TLC, vol. 33, no. 3, pp. 313-319.View/Download from: Publisher's site
© 2020, Akadémiai Kiadó, Budapest, Hungary. The present study was designed to develop and validate a high-performance thin-layer chromatography (HPTLC) system for the simultaneous quantitative determination of berberine and rutin in Tinospora cordifolia extract and their pharmaceutical preparations. Chromatographic development was done using a blend of n-hexane, ethyl acetate, glacial acetic acid and methanol (10:1.1:1.1:2.5, v/v) as the mobile phase. Detection was completed densitometrically at 254 nm. The RF estimation of berberine and rutin was observed to be 0.67 ± 0.02 and 0.47 ± 0.02, respectively. The developed HPTLC method was validated according to ICH guidelines; the method was specific, linear and accurate and can be used to determine berberine and rutin in marketed herbal preparations. The Tinospora cordifolia plant extract was further evaluated for antioxidant activity using HPTLC, and berberine was found to be more active than rutin during DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity. The method was found simple, rapid, accurate, specific and robust for the analysis of berberine and rutin in crude drug using the same method. [Figure not available: see fulltext.]
Sharma, A, Sethi, G, Tambuwala, MM, Aljabali, AAA, Chellappan, DK, Dua, K & Goyal, R 2020, 'Circadian rhythm disruption and Alzheimer's disease: The dynamics of a vicious cycle.', Current neuropharmacology.View/Download from: Publisher's site
All mammalian cells exhibit circadian rhythm in cellular metabolism and energetics. Autonomous cellular clocks are modulated by various pathways that are essential for robust time keeping. In addition to the canonical transcriptional translational feedback loop, several new pathways of circadian timekeeping - non-transcriptional oscillations, post-translational modifications, epigenetics and cellular signaling in the circadian clock - have been identified. The physiology of circadian rhythm is expansive, and its link to the neurodegeneration is multifactorial. Circadian rhythm disruption is prevelant in contamporary society where light-noise, shift-work, and transmeridian travel are commonplace, and is also reported from the early stages of Alzheimer's disease (AD). Circadian alignment by bright light therapy in conjunction with chronobiotics is beneficial for treating sundowning syndrome and other cognitive symptoms in advanced AD patients. We performed a comprehensive analysis of the clinical and translational reports to review the physiology of the circadian clock, delineate its dysfunction in AD, and unravel the dynamics of the vicious cycle between two pathologies. The review delineates the role of putative targets like clock proteins PER, CLOCK, BMAL1, ROR, and clock-controlled proteins like AVP, SIRT1, FOXO, and PK2 towards future approaches for management of AD. Furthermore, the role of circadian rhythm disruption in aging is delineated.
Sharma, AK, Prasher, P, Aljabali, AA, Mishra, V, Gandhi, H, Kumar, S, Mutalik, S, Chellappan, DK, Tambuwala, MM, Dua, K & Kapoor, DN 2020, 'Emerging era of "somes": polymersomes as versatile drug delivery carrier for cancer diagnostics and therapy', Drug Delivery and Translational Research, vol. 10, no. 5, pp. 1171-1190.View/Download from: Publisher's site
© 2020, Controlled Release Society. Over the past two decades, polymersomes have been widely investigated for the delivery of diagnostic and therapeutic agents in cancer therapy. Polymersomes are stable polymeric vesicles, which are prepared using amphiphilic block polymers of different molecular weights. The use of high molecular weight amphiphilic copolymers allows for possible manipulation of membrane characteristics, which in turn enhances the efficiency of drug delivery. Polymersomes are more stable in comparison with liposomes and show less toxicity in vivo. Furthermore, their ability to encapsulate both hydrophilic and hydrophobic drugs, significant biocompatibility, robustness, high colloidal stability, and simple methods for ligands conjugation make polymersomes a promising candidate for therapeutic drug delivery in cancer therapy. This review is focused on current development in the application of polymersomes for cancer therapy and diagnosis. [Figure not available: see fulltext.].
Sharma, M, Prasher, P, Mehta, M, Zacconi, FC, Singh, Y, Kapoor, DN, Dureja, H, Pardhi, DM, Tambuwala, MM, Gupta, G, Chellappan, DK, Dua, K & Satija, S 2020, 'Probing 3CL protease: Rationally designed chemical moieties for COVID-19', DRUG DEVELOPMENT RESEARCH.View/Download from: Publisher's site
Shrivastava, G, Bakshi, HA, Aljabali, AA, Mishra, V, Hakkim, FL, Charbe, NB, Kesharwani, P, Chellappan, DK, Dua, K & Tambuwala, MM 2020, 'Nucleic Acid Aptamers as a Potential Nucleus Targeted Drug Delivery System', CURRENT DRUG DELIVERY, vol. 17, no. 2, pp. 101-111.View/Download from: Publisher's site
Singh, Y, Gupta, G, Kazmi, I, Al-Abbasi, FA, Negi, P, Chellappan, DK & Dua, K 2020, 'SARS CoV-2 aggravates cellular metabolism mediated complications inCOVID-19 infection', DERMATOLOGIC THERAPY.View/Download from: Publisher's site
Singh, Y, Gupta, G, Mishra, A, Chellappan, DK & Dua, K 2020, 'Gender and Age Differences Reveal Risk Patterns in COVID-19 Outbreak.', Alternative therapies in health and medicine, vol. 26, no. S2, pp. 54-55.
By April 28th 2020, the global number of people that were viciously infected with the newfound novel corona virus (COVID-19) stood at a staggering 3 077 133 cases, as per the confirmed data released by the WHO. It has been reported that women from the Chinese Han population are associated with essential hypertension due to their relation with the 5 SNPs, namely, rs1514283, rs4646155, rs4646176, rs2285666, and rs879922, which belong to the ACE2 gene. The level of ACE2 activity was very low in normal healthy younger persons, and was reported to be increased in patients with cardiovascular diseases. Thus, there might be severe myocarditis, that may result in acute heart failure and cardiac complexities in the elderly subjects.
Singh, Y, Gupta, G, Satija, S, Negi, P, Chellappan, DK & Dua, K 2020, 'RAAS blockers in hypertension posing a higher risk toward the COVID-19.', Dermatologic therapy, pp. e13501-e13501.View/Download from: Publisher's site
Singh, Y, Gupta, G, Satija, S, Pabreja, K, Chellappan, DK & Dua, K 2020, 'COVID-19 transmission through host cell directed network of GPCR', DRUG DEVELOPMENT RESEARCH, vol. 81, no. 6, pp. 647-649.View/Download from: Publisher's site
Soon, L, Ng, PQ, Chellian, J, Madheswaran, T, Panneerselvam, J, Hsu, A, Hansbro, PM, Dua, K, Collet, T & Chellappan, DK 2020, 'Green synthesis and antibacterial potential of artemisia vulgaris extract in silver nanoparticles against wound bacteria', Jurnal Ilmiah Farmasi, vol. 16, no. 1, pp. 9-18.View/Download from: Publisher's site
Tan, YY, Yap, PK, Xin Lim, GL, Mehta, M, Chan, Y, Ng, SW, Kapoor, DN, Negi, P, Anand, K, Singh, SK, Jha, NK, Lim, LC, Madheswaran, T, Satija, S, Gupta, G, Dua, K & Chellappan, DK 2020, 'Perspectives and advancements in the design of nanomaterials for targeted cancer theranostics.', Chemico-biological interactions, vol. 329.View/Download from: Publisher's site
Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics properties of the...
Tew, XN, Xin Lau, NJ, Chellappan, DK, Madheswaran, T, Zeeshan, F, Tambuwala, MM, Aljabali, AA, Balusamy, SR, Perumalsamy, H, Gupta, G, Oliver, BG, Hsu, A, Wark, P, Reddy, K, Wadhwa, R, Hansbro, PM & Dua, K 2020, 'Immunological axis of berberine in managing inflammation underlying chronic respiratory inflammatory diseases.', Chemico-biological interactions, vol. 317.View/Download from: Publisher's site
Inflammatory responses play a remarkable role in the mechanisms of acute and chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis and lung cancer. Currently, there is a resurgence in the use of drugs from natural sources for various ailments as potent therapeutics. Berberine, an alkaloid prominent in the Chinese traditional system of medicine has been reported to exert therapeutic properties in various diseases. Nevertheless, the number of studies focusing on the curative potential of berberine in inflammatory diseases involving the respiratory system is limited. In this review, we have attempted to discuss the reported anti-inflammatory properties of berberine that function through several pathways such as, the NF-κB, ERK1/2 and p38 MAPK pathways which affect several pro-inflammatory cytokines in the pathophysiological processes involved in chronic respiratory diseases. This review would serve to provide valuable information to researchers who work in this field and a new direction in the field of drug discovery with respect to respiratory diseases.
Thakur, AK, Chellappan, DK, Dua, K, Mehta, M, Satija, S & Singh, I 2020, 'Patented therapeutic drug delivery strategies for targeting pulmonary diseases.', Expert opinion on therapeutic patents, vol. 30, no. 5, pp. 375-387.View/Download from: Publisher's site
Introduction: Pulmonary route is one of the preferred routes for the administration of therapeutically active agents for systemic as well as localized delivery. Chronic obstructive pulmonary disease (COPD), bronchial asthma, pneumonia, pulmonary hypertension, bronchiolitis, lung cancer, and tuberculosis are the major chronic diseases associated with the pulmonary system. Knowledge about the affecting factors, namely, the etiology, pathophysiology, and the various barriers (mechanical, chemical, immunological, and behavioral) in pulmonary drug delivery is essential to develop an effective drug delivery system. Formulation strategies and mechanisms of particle deposition in the lungs also play an important role in designing a suitable delivery system.Areas covered: In the present paper, various drug delivery strategies, viz. nanoparticles, microparticles, liposomes, powders, and microemulsions have been discussed systematically, from a patent perspective.Expert opinion: Patent publications on formulation strategies have been instrumental in the evolution of new techniques and technologies for safe and effective treatment of pulmonary diseases. New delivery systems are required to be simple/reproducible/scalable/cost-effective scale for manufacturing ability and should be safe/effective/stable/controllable for meeting quality and regulatory compliance.
Thangavelu, L, Balusamy, SR, Shanmugam, R, Sivanesan, S, Devaraj, E, Rajagopalan, V, Veeraiyan, DN, Chellappan, DK, Dua, K, Kim, Y-J & Perumalsamy, H 2020, 'Evaluation of the sub-acute toxicity of Acacia catechu Willd seed extract in a Wistar albino rat model.', Regulatory toxicology and pharmacology : RTP, vol. 113.View/Download from: Publisher's site
Acacia catechu (A. catechu) or Khair (Hindi) is used in several herbal preparations in the Ayurvedic system of medicine in India. Traditionally, this drug is beneficial against several gastrointestinal and stomach related ailments, and leprosy. The present investigation was carried out to evaluate the sub-acute oral toxicity of the ethanolic extract of A. catechu seeds in Wistar albino rats. Results obtained from the quantitative chemical analysis of A. catechu seed extract were compared with commercially available standards. A. catechu seed extract was administered orally at the doses of 250, 500 and 1000 mg/kg b.w. daily for 28 days. General behavior, bodyweight and mortality were examined during the entire study period. At the end of 28 days, hematological and biochemical parameters along with the relative organ weights were determined. It was observed that the extract did not induce death or any significant changes in the body weight, relative weight of vital organs and in hematological parameters for up to a dose of 1000 mg/kg. The oral administration of the plant extract did not produce any significant changes in the levels of glucose. In addition, there were no significant changes in the activity of both hepatotoxic and nephrotoxic marker enzymes in the serum. Oral administration of A. catechu also did not produce any significant changes in the levels of oxidative markers. Furthermore, the findings from the biochemical studies were, well corroborated with the histological findings.
Wadhwa, R, Paudel, KR, Mehta, M, Shukla, SD, Sunkara, K, Prasher, P, Panth, N, Goyal, R, Chellappan, DK, Gupta, G, Hansbro, PM, Aljabali, AAA & Dua, K 2020, 'Beyond the obvious: Smoking and respiratory infection implications on Alzheimer's disease', CNS & Neurological Disorders - Drug Targets, vol. 19.View/Download from: Publisher's site
Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders,
lung and oral cancers but also causes neurological disorders such as Alzheimer's disease. Tobacco smoke consists of more than 4500 toxic
chemicals, which form free radicals and can cross blood brain barrier resulting in oxidative stress, an extracellular amyloid plaque from the
aggregation of amyloid β (Aβ) peptide deposition in the brain. Further, respiratory infections such as Chlamydia pneumoniae, respiratory
syncytial virus have also been involved in the induction and development of the disease.
The necessary information collated on this review has been gathered from various literature published from 1995 to 2019.
The review article sheds light on the role of smoking and respiratory infections in causing oxidative stress and neuroinflammation resulting in Alzheimer's disease (AD). This review will be of interest to scientists and researchers from biological and medical science
disciplines including microbiology, pharmaceutical sciences and the translational researchers, etc.
The increasing understanding of the relationship between chronic lung disease and neurological disease are two-fold. First,
this would help to identify the risk factors and possible therapeutic interventions to reduce the development and progression of both
diseases. Second, this would help to reduce the probable risk of development of AD in the population prone to chronic lung diseases.
Waghule, T, Sankar, S, Rapalli, VK, Gorantla, S, Dubey, SK, Chellappan, DK, Dua, K & Singhvi, G 2020, 'Emerging role of nanocarriers based topical delivery of anti-fungal agents in combating growing fungal infections', Dermatologic Therapy.View/Download from: Publisher's site
© 2020 Wiley Periodicals LLC. The incidences of fungal infections have greatly increased over the past few years, particularly in humid and industrialized areas. The severity of such infections ranges from being asymptomatic-mild to potentially life-threatening systemic infections. There are limited classes of drugs that are approved for the treatment of such infections like polyenes, azoles, and echinocandins. Some fungi have developed resistance to these drugs. Therefore, to counter drug resistance, intensive large scale studies on novel targeting strategies and formulations are being conducted, which have gained impetus lately. Conventional formulations have limitations such as higher doses, frequent dosing, and several side effects. Such limiting factors have paved the path for the emergence of nanotechnology and its applications. This further gave formulation scientists the possibility of encapsulating the existing potential drug moieties into nanocarriers, which when loaded into gels or creams provided prolonged release and improved permeation, thus giving on-target effect. This review thus discusses the newer targeting strategies and the role of nanocarriers that could be administered topically for the treatment of various fungal infections. Furthermore, this approach opens newer avenues for continued and sustained research in pharmaceuticals with much more effective outcomes.
Chan, Y, Ng, SW, Chellappan, DK, Madheswaran, T, Zeeshan, F, Kumar, P, Pillay, V, Gupta, G, Wadhwa, R, Mehta, M, Wark, P, Hsu, A, Hansbro, NG, Hansbro, PM, Dua, K & Panneerselvam, J 2020, 'Celastrol-loaded liquid crystalline nanoparticles as an anti-inflammatory intervention for the treatment of asthma', INTERNATIONAL JOURNAL OF POLYMERIC MATERIALS AND POLYMERIC BIOMATERIALS.View/Download from: Publisher's site
Mehta, M, Chellappan, DK, Wich, PR, Hansbro, NG, Hansbro, PM & Dua, K 2020, 'miRNA nanotherapeutics: potential and challenges in respiratory disorders', Future medicinal chemistry, vol. 12, no. 11, pp. 987-990.View/Download from: Publisher's site
Prasher, P, Sharma, M, Mehta, M, Paudel, KR, Satija, S, Chellappan, DK, Dureja, H, Gupta, G, Tambuwala, MM, Negi, P, Wich, PR, Hansbro, NG, Hansbro, PM & Dua, K 2020, 'Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective.', Chemico-biological interactions, vol. 325.View/Download from: Publisher's site
The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders.
Yong, DOC, Saker, SR, Chellappan, DK, Madheswaran, T, Panneerselvam, J, Choudhury, H, Pandey, M, Chan, YL, Collet, T, Gupta, G, Oliver, BG, Wark, P, Hansbro, N, Hsu, A, Hansbro, PM, Dua, K & Zeeshan, F 2020, 'Molecular and Immunological Mechanisms Underlying the Various Pharmacological Properties of the Potent Bioflavonoid, Rutin.', Endocrine, metabolic & immune disorders drug targets.View/Download from: Publisher's site
The application of medicinal plants has captured the interest of researchers in recent times due to their potent therapeutic properties and a better safety profile. The prominent role of herbal products in treating and preventing multiple diseases dates back to ancient history and most of the modern drugs today originated from its significant sources owing to their ability to control multiple targets via different signalling pathways. Among them, flavonoids consist of a large group of polyphenols, which are well known for their various therapeutic benefits. Rutin is considered one of the attractive phytochemicals and important flavonoid in the pharmaceutical industry due to its diverse pharmacological activities via various underlying molecular mechanisms. It is usually prescribed for various disease conditions such as varicosities, haemorrhoids and internal haemorrhage. In this review, we have discussed and highlighted the different molecular mechanisms attributed to the various pharmacological activities of rutin such as antioxidant, anti-inflammatory, anticancer, anti-allergic and anti-diabetic. This review will be beneficial to herbal, biological and molecular scientists in understanding the pharmacological relevance of rutin at the molecular level.
Paudel, KR, Dharwal, V, Patel, V, Galvao, I, Wadhwa, R, Malyla, V, Shen, S, Budden, KF, Hansbro, N, Bebawy, M, Dua, K & Hansbro, P 2020, 'Role of lung microbiome in innate immune response associated with chronic lung diseases', Frontiers in Medicine.
Xu, J, Xu, X, Jiang, L, Dua, K, Hansbro, PM & Liu, G 2020, 'SARS-CoV-2 induces transcriptional signatures in human lung epithelial cells that promote lung fibrosis.', Respiratory research, vol. 21, no. 1.View/Download from: Publisher's site
BACKGROUND:Severe acute respiratory syndrome (SARS)-CoV-2-induced coronavirus disease-2019 (COVID-19) is a pandemic disease that affects > 2.8 million people worldwide, with numbers increasing dramatically daily. However, there is no specific treatment for COVID-19 and much remains unknown about this disease. Angiotensin-converting enzyme (ACE)2 is a cellular receptor of SARS-CoV-2. It is cleaved by type II transmembrane serine protease (TMPRSS)2 and disintegrin and metallopeptidase domain (ADAM)17 to assist viral entry into host cells. Clinically, SARS-CoV-2 infection may result in acute lung injury and lung fibrosis, but the underlying mechanisms of COVID-19 induced lung fibrosis are not fully understood. METHODS:The networks of ACE2 and its interacting molecules were identified using bioinformatic methods. Their gene and protein expressions were measured in human epithelial cells after 24 h SARS-CoV-2 infection, or in existing datasets of lung fibrosis patients. RESULTS:We confirmed the binding of SARS-CoV-2 and ACE2 by bioinformatic analysis. TMPRSS2, ADAM17, tissue inhibitor of metalloproteinase (TIMP)3, angiotensinogen (AGT), transformation growth factor beta (TGFB1), connective tissue growth factor (CTGF), vascular endothelial growth factor (VEGF) A and fibronectin (FN) were interacted with ACE2, and the mRNA and protein of these molecules were expressed in lung epithelial cells. SARS-CoV-2 infection increased ACE2, TGFB1, CTGF and FN1 mRNA that were drivers of lung fibrosis. These changes were also found in lung tissues from lung fibrosis patients. CONCLUSIONS:Therefore, SARS-CoV-2 binds with ACE2 and activates fibrosis-related genes and processes to induce lung fibrosis.
Usman, B, Sharma, N, Satija, S, Mehta, M, Vyas, M, Khatik, GL, Khurana, N, Hansbro, PM, Williams, K & Dua, K 2019, 'Recent Developments in Alpha-Glucosidase Inhibitors for Management of Type-2 Diabetes: An Update', CURRENT PHARMACEUTICAL DESIGN, vol. 25, no. 23, pp. 2510-2525.View/Download from: Publisher's site
Bakshi, HA, Mishra, V, Satija, S, Mehta, M, Hakkim, FL, Kesharwani, P, Dua, K, Chellappan, DK, Charbe, NB, Shrivastava, G, Rajeshkumar, S, Aljabali, AA, Al-Trad, B, Pabreja, K & Tambuwala, MM 2019, 'Dynamics of Prolyl Hydroxylases Levels During Disease Progression in Experimental Colitis', INFLAMMATION, vol. 42, no. 6, pp. 2032-2036.View/Download from: Publisher's site
Bugno, A, Almodovar, AAB, Saes, DPS, Awasthi, R, Ghisleni, DDM, de Souza Braga, M, de Oliveira, WA, Dua, K & de Jesus Andreoli Pinto, T 2019, 'Evaluation of an Amplified ATP Bioluminescence Method for Rapid Sterility Testing of Large Volume Parenteral', Journal of Pharmaceutical Innovation, vol. 14, pp. 152-158.View/Download from: Publisher's site
© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The sterility test described in pharmacopeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the Celsis AKuScreen™ Advance™ system, is particularly interesting because it allows a reduced incubation period and higher efficiency. The present study was aimed to evaluate and compare the performance of Celsis AKuScreen™ Advance™ system with the pharmacopeial sterility test. There was no significant difference between the ability of detection of microbial contamination observed within pharmacopeial method and test method. The Celsis AKuScreen™ Advance™ system allowed a faster detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.
Chellappan, DK, Sze Ning, QL, Su Min, SK, Bin, SY, Chern, PJ, Shi, TP, Ee Mei, SW, Yee, TH, Qi, OJ, Thangavelu, L, Rajeshkumar, S, Negi, P, Chellian, J, Wadhwa, R, Gupta, G, Collet, T, Hansbro, PM & Dua, K 2019, 'Interactions between microbiome and lungs: Paving new paths for microbiome based bio-engineered drug delivery systems in chronic respiratory diseases.', Chemico-biological interactions, vol. 310.View/Download from: Publisher's site
BACKGROUND:The human body is a home to thousands of microbiotas. It is defined as a community of symbiotic, commensal and pathogenic microorganisms that have existed in all exposed sites of the body, which have co-evolved with diet, lifestyle, genetic factors and immune factors. Human microbiotas have been studied for years on their effects with relation to health and diseases. METHODS:Relevant published studies, literature and reports were searched from accessible electronic databases and related institutional databases. We used keywords, viz; microbiome, microbiota, microbiome drug delivery and respiratory disease. Selected articles were carefully read through, clustered, segregated into subtopics and reviewed. FINDINGS:The traditional belief of sterile lungs was challenged by the emergence of culture-independent molecular techniques and the recently introduced invasive broncho-alveolar lavage (BAL) sampling method. The constitution of a lung microbiome mainly depends on three main ecological factors, which include; firstly, the immigration of microbes into airways, secondly, the removal of microbes from airways and lastly, the regional growth conditions. In healthy conditions, the microbial communities that co-exist in our lungs can build significant pulmonary immunity and could act as a barrier against diseases, whereas, in an adverse way, microbiomes may interact with other pathogenic bacteriomes and viromes, acting as a cofactor in inflammation and host immune responses, which may lead to the progression of a disease. Thus, the use of microbiota as a target, and as a drug delivery system in the possible modification of a disease state, has started to gain massive attention in recent years. Microbiota, owing to its unique characteristics, could serve as a potential drug delivery system, that could be bioengineered to suit the interest. The engineered microbiome-derived therapeutics can be delivered through BC, bacteriophage, bacteria-derived lipid vesicles a...
Chellappan, DK, Yee, NJ, Kaur Ambar Jeet Singh, BJ, Panneerselvam, J, Madheswaran, T, Chellian, J, Satija, S, Mehta, M, Gulati, M, Gupta, G & Dua, K 2019, 'Formulation and characterization of glibenclamide and quercetin-loaded chitosan nanogels targeting skin permeation.', Therapeutic Delivery, vol. 10, no. 5, pp. 281-293.View/Download from: Publisher's site
Aim: Our aim was to develop and characterize a nanogel formulation containing both glibenclamide and quercetin and to explore the permeation profile of this combination. Methods: Drug-loaded nanogel was prepared by ionic gelation. In addition, optimum encapsulation efficiencies of glibenclamide and quercetin were also obtained. The average nanoparticle size at optimum conditions was determined by Zetasizer. Results: The particle size of the nanogel was found to be 370.4 ± 4.78 nm with a polydispersity index of 0.528 ± 0.04, while the λ potential was positive in a range of 17.6 to 24.8 mV. The percentage cumulative drug release also showed favorable findings. Conclusion: The chitosan nanogel could be a potential alternative for delivering glibenclamide and quercetin through skin.
Cherk Yong, DO, Saker, SR, Wadhwa, R, Chellappan, DK, Madheswaran, T, Panneerselvam, J, Tambuwala, MM, Bakshi, HA, Kumar, P, Pillay, V, Gupta, G, Oliver, BG, Wark, P, Hsu, A, Hansbro, PM, Dua, K & Zeeshan, F 2019, 'Preparation, characterization and in-vitro efficacy of quercetin loaded liquid crystalline nanoparticles for the treatment of asthma', Journal of Drug Delivery Science and Technology, vol. 54.View/Download from: Publisher's site
© 2019 Elsevier B.V. The present study aims to formulate quercetin loaded liquid crystalline nanoparticles (LCN) and surface modified liquid crystalline nanoparticles (sm-LCN) as well as investigate their anti-inflammatory activity in human primary bronchial epithelial cell line (BCi-NS1.1) induced with lipopolysaccharide (LPS). Quercetin LCN were prepared using ultrasonication method. The formulated LCNs and sm-LCNs were characterised in terms of particle size, zeta potential as well as the drug encapsulation efficiency. Furthermore, their morphology and in vitro release profile were also studied. In addition, the anti-inflammatory activity of quercetin LCN and sm-LCNs were evaluated by measuring the concentration of pro-inflammatory markers namely interleukin (IL)-1β, IL-6 and IL-8 in BCI-NS1.1 cell lines via cytometric bead array. The molecular mechanism inherent to the inclusion of quercetin into monoolein nanosystem and surface modification of the nanosystem with chitosan was elucidated via molecular mechanics simulations. Quercetin LCN and sm-LCN significantly (p < 0.05) decreased the production of IL-1β, IL-6 and IL-8 compared to LPS only group. Encapsulation of quercetin into LCN and sm-LCN further enhanced its anti-inflammatory activity compared to quercetin in dimethyl sulfoxide (DMSO). In addition to that, quercetin LCN and sm-LCN also exhibited comparable activity to fluticasone in terms of significantly (p < 0.05) reducing the production of IL-1β and IL-6. Quercetin loaded LCN and sm-LCN could be a potential therapeutic intervention for asthma as they are efficacious in suppressing the production of key pro-inflammatory cytokines associated with the development of asthma.
Dighe, SN, Ekwudu, O, Dua, K, Chellappan, DK, Katavic, PL & Collet, TA 2019, 'Recent update on anti-dengue drug discovery.', European journal of medicinal chemistry, vol. 176, pp. 431-455.View/Download from: Publisher's site
Dengue is the most important arthropod-borne viral disease of humans, with more than half of the global population living in at-risk areas. Despite the negative impact on public health, there are no antiviral therapies available, and the only licensed vaccine, Dengvaxia®, has been contraindicated in children below nine years of age. In an effort to combat dengue, several small molecules have entered into human clinical trials. Here, we review anti-DENV molecules and their drug targets that have been published within the past five years (2014-2018). Further, we discuss their probable mechanisms of action and describe a role for classes of clinically approved drugs and also an unclassified class of anti-DENV agents. This review aims to enhance our understanding of novel agents and their cognate targets in furthering innovations in the use of small molecules for dengue drug therapies.
Dua, K, Wadhwa, R, Singhvi, G, Rapalli, V, Shukla, SD, Shastri, MD, Gupta, G, Satija, S, Mehta, M, Khurana, N, Awasthi, R, Maurya, PK, Thangavelu, L, Rajeshkumar, S, Tambuwala, MM, Collet, T, Hansbro, PM & Chellappan, DK 2019, 'The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress', Drug Development Research, vol. 80, pp. 714-730.View/Download from: Publisher's site
© 2019 Wiley Periodicals, Inc. Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
Gautam, RK, Gupta, G, Sharma, S, Hatware, K, Patil, K, Sharma, K, Goyal, S, Chellappan, DK & Dua, K 2019, 'Rosmarinic acid attenuates inflammation in experimentally induced arthritis in Wistar rats, using Freund's complete adjuvant.', International journal of rheumatic diseases, vol. 22, no. 7, pp. 1247-1254.View/Download from: Publisher's site
AIM:The purpose of our investigation is to evaluate the anti-arthritic potential of isolated rosmarinic acid from the rind of Punica granatum. METHOD:Rosmarinic acid was isolated by bioactivity-guided isolation from butanolic fraction of Punica granatum and acute toxicity of rosmarinic acid was carried out. The experiment was conducted at doses of 25 and 50 mg/kg, in Freund's complete adjuvant (FCA)-induced arthritic rats. Various parameters, that is arthritic score, paw volume, thickness of paw, hematological, antioxidant and inflammatory parameters such as glutathione (GSH), superoxide dismutase (SOD), malonaldehyde (MDA) and tumor necrosis factor-α (TNF-α) were also estimated. RESULTS:Rosmarinic acid significantly decreased the arthritic score, paw volume, joint diameter, white blood cell count and erythrocyte sedimentation rate. It also significantly increased body weight, hemoglobin and red blood cells. The significantly decreased levels of TNF-α were observed in treated groups as compared to arthritic control rats (P < 0.001). At the same time antioxidant parameters (like GSH and SOD) were increased significantly while levels of MDA were significantly decreased (P < 0.001). CONCLUSION:The outcome of the present research concludes that rosmarinic acid showed significant anti-arthritic potential in FCA-induced arthritis in Wistar rats. This study represented the therapeutic role of rosmarinic acid from Punica granatum for the management of arthritis/rheumatoid arthritis/osteoarthritis and related inflammatory complications with negligible side effects which was still far from complete mitigation with available conventional medicines.
Gupta, G, Pathak, S, Dahiya, R, Awasthi, R, Mishra, A, Sharma, RK, Agrawal, M & Dua, K 2019, 'Aqueous Extract of Wood Ear Mushroom, Auricularia polytricha (Agaricomycetes), Demonstrated Antiepileptic Activity against Seizure Induced by Maximal Electroshock and Isoniazid in Experimental Animals.', International journal of medicinal mushrooms, vol. 21, no. 1, pp. 29-35.View/Download from: Publisher's site
Auricularia polytricha is a popular mushroom found all over the world. This article describes a study of the antiepileptic effect of A. polytricha, a mushroom that is used traditionally for treating asthma, rheumatism, tumors, cough, fever, and epilepsy, and for its antimicrobial effect. We carried out toxicity studies to identify a standard dose of A. polytricha aqueous extract; maximal electroshock (MES)- and isoniazid (INH)-induced seizures in albino mice were used to screen for the extract's antiepileptic activity. Per Organisation for Economic Co-operation and Development Guideline 423, up to 2000 mg/kg body weight of extract was toxic. Animals were treated with aqueous extract at doses of 200, 400, and 600 mg/kg body weight. Phenytoin was used as the reference anticonvulsant drug for comparison. The investigation found a significant interruption in INH-induced clonic seizure. During MES, we found a reduction in the period of hind leg extensor phase; mice exhibited a significant decrease in the duration of hind limb extension after being treated with 400 and 600 mg/kg doses of A. polytricha. Comparable results were obtained in the INH group, as the extract seemed to delay the onset of a clonic seizure. The aqueous extract of A. polytricha showed antiepileptic action against MES- and INH-induced epilepsy in the mice. This extract, however, requires additional study in order to completely explain its active ingredients and their mechanisms of action.
Khursheed, R, Singh, SK, Wadhwa, S, Kapoor, B, Gulati, M, Kumar, R, Ramanunny, AK, Awasthi, A & Dua, K 2019, 'Treatment strategies against diabetes: Success so far and challenges ahead.', European journal of pharmacology, vol. 862.View/Download from: Publisher's site
The growing disease burden of diabetes mellitus is an important public health concern, affecting over 400 million people globally. This epidemic, if not controlled in time, leads to life threatening complications, compromise in quality of life, and eventually mortality. Over time, many attempts have been made for the effective treatment of diabetes but true success has never been achieved. Pharmacological and non-pharmacological approaches for the treatment of hyperglycaemia have been ever-evolving due to limitations of current therapies. Non pharmacological management which includes diet management and exercise, has been the primary focus for self-management of diabetes. The pharmacological management includes oral antihyperglycaemics, phytoconstituents, and combination products. Advancements such as nanocarrier delivery systems have been made in drug delivery to overcome the challenges such as poor bioavailability associated with conventional dosage forms currently employed in diabetes treatment. In recent years, much emphasis has been given to synbiotics that act on gut microbiota, as an emerging therapy for diabetes. The current review discusses different treatment strategies for diabetes management starting from insulin therapy to synbiotics. The combination of herbal phytoconstituents with synthetic drugs, synthetic drug combinations, novel drug delivery systems for insulin are highlighted. Moreover, the role of gut dysbiosis in diabetes and its treatment by administration of synbiotics in various clinical as well as non clinical studies has been discussed in detail.
Kumari, Y, Kaur, G, Kumar, R, Singh, SK, Gulati, M, Khursheed, R, Clarisse, A, Gowthamarajan, K, Karri, VVSNR, Mahalingam, R, Ghosh, D, Awasthi, A, Kumar, R, Yadav, AK, Kapoor, B, Singh, PK, Dua, K & Porwal, O 2019, 'Gold nanoparticles: New routes across old boundaries.', Advances in colloid and interface science, vol. 274.View/Download from: Publisher's site
In recent years, gold nanoparticles have emerged as unique non-invasive drug carriers for targeting drugs to their site of action. Their site specificity has helped in increasing drugs' efficacy at lower dose as well as reduction in their side effects. Moreover, their excellent optical properties and small size offer their utilization as diagnostic tools to diagnose tumors as well as other diseases. This review focuses on various approaches that have been used in last several years for preparation of gold nanoparticles, their characterization techniques and theranostic applications. Their toxicity related aspects are also highlighted. Gold nanoparticles are useful as theranostic agents, owing to their small size, biocompatible nature, size dependent physical, chemical and optical properties etc. However, the challenges associated with these nanoparticles such as scale up, cost, low drug payload, toxicity and stability have been the major impediments in their commercialization. The review looks into all these critical issues and identifies the possibilities to overcome these challenges for successful positioning of metallic nanoparticles in market.
Mehta, DK, Taya, P, Das, R & Dua, K 2019, 'Design, Synthesis and Molecular Docking Studies of Novel Thiadiazole Analogues with Potential Antimicrobial and Antiinflammatory Activities.', Anti-inflammatory & anti-allergy agents in medicinal chemistry, vol. 18, no. 2, pp. 91-109.View/Download from: Publisher's site
BACKGROUND:Chemical modification of thiadiazole may lead to a potent therapeutic agent. In this study, biological properties of thiadiazole derivatives were evaluated by assessing their antimicrobial and anti-inflammatory activities. METHODS:A series of novel derivatives of N-(5-(1-methyl-indol-3-yl)-1,3,4-thiadiazol-2- yl)-2-(5-substitutedphenyl)-3-(phenylamino)-4,5-dihydropyrazol-1-yl) acetamide have been synthesized and evaluated for their antimicrobial activity. Anti-inflammatory activity was done using carrageenan-induced inflammation in rat paw edema model. In-silico molecular docking studies of the synthesized compounds were performed on crystal structures of Aspergillus niger, Bacillus subtilis, Candida albicans, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Cyclooxygenase-2 (obtained from www.rcsb.org) using GRIP batch docking method of V-life MDS 3.0 software. The structures of the newly synthesized compounds were confirmed by FT-IR, 1H-NMR, 13C-NMR and Mass spectroscopy. RESULTS:Antimicrobial and Anti-inflammatory activity study of the novel synthesized compounds were screened. Synthesized compounds having methoxy substitution on the 3rd and 4th positions of aromatic ring are utmost active amongst all the derivatives. Compounds 6d, 6i, 6j and 6l were found to possess good anti-inflammatory activity having percentage of inhibition to the extent of 46.8%, 48.1%, 49.4%, and 48.5% as compared with Diclofenac. CONCLUSION:The experimental results were further supported by molecular docking analysis describing the better interaction patterns.
Mehta, M, Deeksha, Sharma, N, Vyas, M, Khurana, N, Maurya, PK, Singh, H, Andreoli de Jesus, TP, Dureja, H, Chellappan, DK, Gupta, G, Wadhwa, R, Collet, T, Hansbro, PM, Dua, K & Satija, S 2019, 'Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases.', Chemico-biological interactions, vol. 304, pp. 10-19.View/Download from: Publisher's site
Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.
Mehta, M, Deeksha, Tewari, D, Gupta, G, Awasthi, R, Singh, H, Pandey, P, Chellappan, DK, Wadhwa, R, Collet, T, Hansbro, PM, Kumar, SR, Thangavelu, L, Negi, P, Dua, K & Satija, S 2019, 'Oligonucleotide therapy: An emerging focus area for drug delivery in chronic inflammatory respiratory diseases.', Chemico-biological interactions, vol. 308, pp. 206-215.View/Download from: Publisher's site
Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases.
Mehta, M, Garg, M, Dua, K & Satija, S 2019, 'Simultaneous HPTLC densitometric estimation of KBA and AKBA from Boswellia serrata', Current Analytical Chemistry, vol. 15, no. 1, pp. 84-91.View/Download from: Publisher's site
© 2019 Bentham Science Publishers. Background: Boswellic acids (BAs) are extracted from oleo gum of Boswellia serrata and are utilized as potential anti-inflammatory, hypolipidemic, immunomodulatory and antitumor specialists. The present examination was meant to assess KBA and AKBA in Boswellia serrata separate by High-Performance Thin Layer Chromatography (HPTLC). Methods: The separation of bioactive compounds was performed utilizing mobile phase glacial acetic acid, n-hexane, ethyl acetate and toluene (0.3: 1: 8: 2) (v/v/v/v) and distinguished at wavelength 254 nm. The technique was approved for linearity, precision, accuracy, limit of detection (LOD), limit of quantification (LOQ), and so forth by International Conference on Harmonization guidelines. Results: The calibration range was observed to be 2-14 µg/band for both the bioactive compounds. KBA was isolated with an R f estimation of 0.39 ± 0.02 and AKBA with an R f estimation of 0.42 ± 0.02. The accuracy was seen to be as high as 99.17% and 97.42 for KBA and KBA, respectively. The percentage RSD value for intra-day and between day varieties was under 2%. The system indicated high affectability and specificity. Conclusion: The developed HPTLC method was simple, precise, robust, specific, rapid, and costeffective and could be used for quality control analysis and quantification of KBA and AKBA in different herbal formulations containing the plant species.
Mohanta, S, Singh, SK, Kumar, B, Gulati, M, Kumar, R, Yadav, AK, Wadhwa, S, Jyoti, J, Som, S, Dua, K & Pandey, NK 2019, 'Efficacy of co-administration of modified apple polysaccharide and probiotics in guar gum-Eudragit S100 based mesalamine mini tablets: A novel approach in treating ulcerative colitis.', International Journal of Biological Macromolecules, vol. 126, pp. 427-435.View/Download from: Publisher's site
Modified Apple Polysaccharide (MAP) has been reported to cure colorectal diseases by up-regulating apoptosis and down regulating metastasis. In the present study, mesalamine (MES) and MAP mini tablets have been prepared and co-administered with probiotics to provide site specific release of drug. Probiotics along with MAP, which acts as a prebiotic would replenish the colonic microflora that have been compromised due to colorectal pathology. MES mini tablets were prepared keeping guar gum in the core and coating them with Eudragit S100 and guar gum. The optimized batch was explored for its curative potential on acetic acid induced ulcerative colitis (UC) in rat model with and without administration of probiotic and MAP. The results revealed that the rats treated with the combination of MAP and MES mini tablets along with probiotics show maximum curative potential. It was also observed that MAP mini tablets show better curative potential as compared to probiotics. The results of disease activity index, macroscopic scoring, antioxidant studies, tumour alpha and histopathological examination suggested that the rats treated with combination of MES-MAP mini tablets and probiotics have maximum therapeutic effect followed by MES mini tablets alone, MAP mini tablets alone and probiotics.
Pandey, P, Chellappan, DK, Tambuwala, MM, Bakshi, HA, Dua, K & Dureja, H 2019, 'Central composite designed formulation, characterization and in vitro cytotoxic effect of erlotinib loaded chitosan nanoparticulate system.', International journal of biological macromolecules, vol. 141, pp. 596-610.View/Download from: Publisher's site
The most common cause of deaths due to cancers nowadays is lung cancer. The objective of this study was to prepare erlotinib loaded chitosan nanoparticles for their anticancer potential. To study the effect of formulation variables on prepared nanoparticles using central composite design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using probe sonication technique. It was found that batch NP-7 has a maximum loading capacity and entrapment efficiency with a particle size (138.5 nm) which is ideal for targeting solid tumors. Analysis of variance was applied to the particle size, entrapment efficiency and percent cumulative drug release to study the fitting and the significance of the model. The batch NP-7 showed 91.57% and 39.78% drug release after 24 h in 0.1 N hydrochloric acid and Phosphate Buffer (PB) pH 6.8, respectively. The IC50 value of NP-7 evaluated on A549 Lung cancer cells was found to be 6.36 μM. The XRD of NP-7 displayed the existence of erlotinib in the amorphous pattern. The optimized batch released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using sonication technique with suitable particle size, entrapment efficiency and drug release. The formulated nanoparticles can be utilized for the treatment of lung cancer.
Pandey, P, Dua, K & Dureja, H 2019, 'Erlotinib loaded chitosan nanoparticles: Formulation, physicochemical characterization and cytotoxic potential', International Journal of Biological Macromolecules, vol. 139, pp. 1304-1316.View/Download from: Publisher's site
© 2019 Elsevier B.V. Cancer is the major cause of mortality and morbidity throughout the world where >10 million patients with new cases diagnosed every year. The objective of this study was to prepare and evaluate erlotinib loaded chitosan nanoparticles for their anticancer potential. Also, to study the effect of various formulation variables on prepared nanoparticles using box-behnken design. Erlotinib loaded chitosan nanoparticles were prepared by ionic gelation method using the spray drying technique. It was found that batch SNP-9 has a maximum loading capacity (74.45 ± 0.34%) and entrapment efficiency (43 ± 0.57%) with a particle size 170.2 nm. Analysis of variance (ANOVA) was applied on the particle size, entrapment efficiency and % cumulative drug release to study the fitting and the significance of the model. The batch SNP-9 showed 89.46% and 40.12% drug release after 24 h in 0.1 N HCl and Phosphate Buffer (pH 6.8), respectively. The IC50 value of SNP-9 evaluated on A549 Lung cancer cells was found to be 4.41 μM. The optimized formulation was found stable after the six-month study as no considerable transformation was detected. The optimized formulation released erlotinib slowly in comparison to the marketed tablet formulation. Erlotinib loaded chitosan nanoparticles were prepared successfully using spray drying technique with suitable particle size, entrapment efficiency, drug release. The synthesized and optimized nanoparticles were found to possess activity against cancer cells when evaluated in-vitro.
Pradhan, R, Singhvi, G, Dubey, SK, Gupta, G & Dua, K 2019, 'MAPK pathway: a potential target for the treatment of non-small-cell lung carcinoma.', Future medicinal chemistry, vol. 11, no. 8, pp. 793-795.View/Download from: Publisher's site
Rajeshkumar, S, Menon, S, Kumar, VS, Tambuwala, MM, Bakshi, HA, Mehta, M, Satija, S, Gupta, G, Chellappan, DK, Thangavelu, L & Dua, K 2019, 'Antibacterial and antioxidant potential of biosynthesized copper nanoparticles mediated through Cissus arnotiana plant extract', JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, vol. 197.View/Download from: Publisher's site
Sah, SK, Samuel, VP, Dahiya, S, Singh, Y, Gilhotra, RM, Gupta, G, Mishra, A, Sharma, RK, Kumar, GS, SreeHarsha, N, Chellappan, DK & Dua, K 2019, 'A contemporary biological pathway of islet amyloid polypeptide for the management of diabetic dementia.', Chemico-biological interactions, vol. 306, pp. 117-122.View/Download from: Publisher's site
Major challenges of dealing elder patients with diabetes mellitus (DM) are the individualization of consideration in persons with various comorbid types of conditions. In spite of the fact that microvascular and macrovascular problems associated with DM are well documented, there is only a few numbers of reports viewing different conditions, for example, cognitive dysfunction. Cognitive dysfunction is of specific significance due to its effect on self-care and quality of life. All in all, the etiology of cognitive dysfunction in the maturing populace is probably going to be the grouping of ischemic and degenerative pathology. It is likewise trusted that Hyperglycemia is engaged with the system of DM-related cognitive dysfunction. At present, it isn't certain in the case of enhancing glycemic control or utilizing therapeutic agents can enhance the risk of cognitive decay. Amylin was later characterized as an amyloidogenic peptide, confined from a beta cell tumor and called islet amyloid polypeptide (IAPP), and after that, amylin. Conversely, we investigate the beneficial role and hypothesizing the mechanism of amylin related expanding the level and activation of CGRP receptor to enhance the cognition declination amid diabetic dementia.
Salehi, B, Staniak, M, Czopek, K, Stepień, A, Dua, K, Wadhwa, R, Chellappan, DK, Sytar, O, Brestic, M, Bhat, NG, Kumar, NVA, Contreras, MDM, Sharopov, F, Cho, WC & Sharifi-Rad, J 2019, 'The therapeutic potential of the labdane diterpenoid forskolin', Applied Sciences (Switzerland), vol. 9, no. 19.View/Download from: Publisher's site
© 2019 by the authors. Forskolin is mainly found in the root of a plant called Coleus forskohlii (Willd.) Briq., which has been used in the traditional medicine of Indian Ayurvedic and Southeast Asia since ancient times. Forskolin is responsible for the pharmacological activity of this species. Forskolin is a labdane diterpenoid with a wide biological effect. Several studies suggested a positive role of forskolin on heart complications, respiratory disorders, high blood pressure, obesity, and asthma. There are numerous clinical and pre-clinical studies representing the effect of forskolin on the above-mentioned disorders but more clinical studies need to be performed to support its efficacy.
Samuel, VP, Dahiya, R, Singh, Y, Gupta, G, Sah, SK, Gubbiyappa, SK, Chellappan, DK & Dua, K 2019, 'Metformin: A Salutary Candidate for Colorectal Cancer Treatment in Patients with Diabetes', JOURNAL OF ENVIRONMENTAL PATHOLOGY TOXICOLOGY AND ONCOLOGY, vol. 38, no. 2, pp. 133-141.View/Download from: Publisher's site
Samuel, VP, Gupta, G, Dahiya, R, Jain, DA, Mishra, A & Dua, K 2019, 'Current Update on Preclinical and Clinical Studies of Resveratrol, a Naturally Occurring Phenolic Compound.', Critical reviews in eukaryotic gene expression, vol. 29, no. 6, pp. 529-537.View/Download from: Publisher's site
Resveratrol has several therapeutic effects and is a nutraceutical. It was shown to imitate caloric restriction effects, exert anti-inflammatory and antioxidative effects, and affect the development and progression of many diseases through several mechanisms. While there is a wealth of evidence in vitro and in vivo that resveratrol could be a promising therapeutic agent, its potential must be confirmed by preclinical studies and clinical trials. We analyzed the current available preclinical and clinical data on resveratrol's pharmacological action. The bulk of resveratrol's preclinical studies and clinical trials focused on cancer, neurological disorders, cardiovascular diseases, diabetes, nonalcoholic fatty liver disease (NAFLD), and obesity. The latest preclinical studies and clinical trials reported that resveratrol was well tolerated and beneficially influenced biomarkers of disease for neurological disorders, cardiovascular diseases, and diabetes. Nevertheless, in certain types of cancers and in NAFLD, resveratrol had unclear and sometimes even detrimental effects. The major obstacle posed in most preclinical studies and clinical trials was the low bioavailability of resveratrol. This work thus provides useful guidelines for future preclinical and clinical resveratrol study planning and design.
Sharma, P, Mehta, M, Dhanjal, DS, Kaur, S, Gupta, G, Singh, H, Thangavelu, L, Rajeshkumar, S, Tambuwala, M, Bakshi, HA, Chellappan, DK, Dua, K & Satija, S 2019, 'Emerging trends in the novel drug delivery approaches for the treatment of lung cancer.', Chemico-biological interactions, vol. 309.View/Download from: Publisher's site
Cancer is one of the major diseases that cause a high number of deaths globally. Of the major types of cancers, lung cancer is known to be the most chronic form of cancer in the world. The conventional management of lung cancer includes different medical interventions like chemotherapy, surgical removal, and radiation therapy. However, this type of approach lacks specificity and also harms the adjacent normal cells. Lately, nanotechnology has emerged as a promising intervention in the management and treatment of lung cancers. Nanotechnology has revolutionized the existing modalities and focuses primarily on reducing toxicity and improving the bioavailability of anticancer drugs to the target tumor cells. Nanocarrier systems are being currently used extensively to exploit and to overcome the obstructions induced by cancers in the lungs. The nano-carrier-loaded therapeutic drug delivery methods have shown promising potential in treating lung cancer as its target is to control the growth of tumor cells. In this review, various modes of nano drug delivery options like liposomes, dendrimers, quantum dots, carbon nanotubes and metallic nanoparticles have been discussed. Nano-carrier drug delivery systems emerge as a promising approach and thus is expected to provide newer and advanced avenues in cancer therapeutics.
Sheshala, R, Ming, NJ, Kok, YY, Raj Singh, TR & Dua, K 2019, 'Formulation and Characterization of pH Induced in situ Gels Containing Sulfacetamide Sodium for Ocular Drug Delivery: A Combination of Carbopol®/ HPMC Polymer', Indian Journal of Pharmaceutical Education and Research, vol. 53, no. 4, pp. 654-662.View/Download from: Publisher's site
Singh, Y, Samuel, VP, Dahiya, S, Gupta, G, Gillhotra, R, Mishra, A, Singh, M, SreeHarsha, N, Gubbiyappa, SK, Tambuwala, MM, Chellappan, DK & Dual, K 2019, 'Combinational effect of angiotensin receptor blocker and folic acid therapy on uric acid and creatinine level in hyperhomocysteinemia-associated hypertension', BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY, vol. 66, no. 5, pp. 715-719.View/Download from: Publisher's site
Wadhwa, R, Aggarwal, T, Malyla, V, Kumar, N, Gupta, G, Chellappan, DK, Dureja, H, Mehta, M, Satija, S, Gulati, M, Maurya, PK, Collet, T, Hansbro, PM & Dua, K 2019, 'Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease.', Journal of cellular physiology, vol. 234, no. 10, pp. 16703-16723.View/Download from: Publisher's site
Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome-wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9).
Wadhwa, R, Dua, K, Adcock, IM, Horvat, JC, Kim, RY & Hansbro, PM 2019, 'Cellular mechanisms underlying steroid-resistant asthma (vol 28, 190021, 2019)', EUROPEAN RESPIRATORY REVIEW, vol. 28, no. 154.View/Download from: Publisher's site
Wadhwa, R, Dua, K, Adcock, IM, Horvat, JC, Kim, RY & Hansbro, PM 2019, 'Cellular mechanisms underlying steroid-resistant asthma.', European respiratory review : an official journal of the European Respiratory Society, vol. 28, no. 153.View/Download from: Publisher's site
Severe steroid-resistant asthma is clinically important, as patients with this form of the disease do not respond to mainstay corticosteroid therapies. The heterogeneity of this form of asthma and poor understanding of the pathological mechanisms involved hinder the identification of therapeutic targets and the development of more effective therapies. A major limiting factor in the understanding of severe steroid-resistant asthma is the existence of multiple endotypes represented by different immunological and inflammatory phenotypes, particularly in adults. Several clinical and experimental studies have revealed associations between specific respiratory infections and steroid-resistant asthma in adults. Here, we discuss recent findings from other authors as well as our own studies that have developed novel experimental models for interrogating the association between respiratory infections and severe steroid-resistant asthma. These models have enabled the identification of new therapies using macrolides, as well as several novel disease mechanisms, including the microRNA-21/phosphoinositide 3-kinase/histone deacetylase 2 axis and NLRP3 inflammasomes, and highlight the potential of these mechanisms as therapeutic targets.
Wadhwa, R, Pandey, P, Gupta, G, Aggarwal, T, Kumar, N, Mehta, M, Satija, S, Gulati, M, Madan, JR, Dureja, H, Balusamy, SR, Perumalsamy, H, Maurya, PK, Collet, T, Tambuwala, MM, Hansbro, PM, Chellappan, DK & Dua, K 2019, 'Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species.', Current topics in medicinal chemistry, vol. 19, no. 28, pp. 2593-2609.View/Download from: Publisher's site
BACKGROUND:Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections. METHODS:The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. RESULTS:This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.). CONCLUSION:It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.
Waghule, T, Singhvi, G, Dubey, SK, Pandey, MM, Gupta, G, Singh, M & Dua, K 2019, 'Microneedles: A smart approach and increasing potential for transdermal drug delivery system.', Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 109, pp. 1249-1258.View/Download from: Publisher's site
The most widely used methods for transdermal administration of the drugs are hypodermic needles, topical creams, and transdermal patches. The effect of most of the therapeutic agents is limited due to the stratum corneum layer of the skin, which serves as a barrier for the molecules and thus only a few molecules are able to reach the site of action. A new form of delivery system called the microneedles helps to enhance the delivery of the drug through this route and overcoming the various problems associated with the conventional formulations. The primary principle involves disruption of the skin layer, thus creating micron size pathways that lead the drug directly to the epidermis or upper dermis region from where the drug can directly go into the systemic circulation without facing the barrier. This review describes the various potential and applications of the microneedles. The various types of microneedles can be fabricated like solid, dissolving, hydrogel, coated and hollow microneedles. Fabrication method selected depends on the type and material of the microneedle. This system has increased its application to many fields like oligonucleotide delivery, vaccine delivery, insulin delivery, and even in cosmetics. In recent years, many microneedle products are coming into the market. Although a lot of research needs to be done to overcome the various challenges before the microneedles can successfully launch into the market.
Xin, GLL, Khee, YP, Ying, TY, Chellian, J, Gupta, G, Kunnath, AP, Nammi, S, Collet, T, Hansbro, PM, Dua, K & Chellappan, DK 2019, 'Current Status on Immunological Therapies for Type 1 Diabetes Mellitus.', Current diabetes reports, vol. 19, no. 5.View/Download from: Publisher's site
PURPOSE OF REVIEW:Type 1 diabetes (T1D) occurs when there is destruction of beta cells within the islets of Langerhans in the pancreas due to autoimmunity. It is considered a complex disease, and different complications can surface and worsen the condition if T1D is not managed well. Since it is an incurable disease, numerous treatments and therapies have been postulated in order to control T1D by balancing hyperglycemia control while minimizing hypoglycemic episodes. The purpose of this review is to primarily look into the current state of the available immunological therapies and their advantages for the treatment of T1D. RECENT FINDINGS:Over the years, immunological therapy has become the center of attraction to treat T1D. Immunomodulatory approaches on non-antigens involving agents such as cyclosporine A, mycophenolate mofetil, anti-CD20, cytotoxic T cells, anti-TNF, anti-CD3, and anti-thymocyte globulin as well as immunomodulative approaches on antigens such as insulin, glutamic acid decarboxylase, and heat shock protein 60 have been studied. Aside from these two approaches, studies and trials have also been conducted on regulatory T cells, dendritic cells, interleukin 2, interleukin 4, M2 macrophages, and rapamycin/interleukin 2 combination therapy to test their effects on patients with T1D. Many of these agents have successfully suppressed T1D in non-obese diabetic (NOD) mice and in human trials. However, some have shown negative results. To date, the insights into the management of the immune system have been increasing rapidly to search for potential therapies and treatments for T1D. Nevertheless, some of the challenges are still inevitable. A lot of work and effort need to be put into the investigation on T1D through immunological therapy, particularly to reduce complications to improve and enhance clinical outcomes.
Yap, PK, Xin, GLL, Tan, YY, Chellian, J, Gupta, G, Liew, YK, Collet, T, Dua, K & Chellappan, DK 2019, 'Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention', JOURNAL OF PHARMACY AND PHARMACOLOGY, vol. 71, no. 9, pp. 1339-1352.View/Download from: Publisher's site
Dua, K, Malyla, V, Singhvi, G, Wadhwa, R, Krishna, RV, Shukla, SD, Shastri, MD, Chellappan, DK, Maurya, PK, Satija, S, Mehta, M, Gulati, M, Hansbro, N, Collet, T, Awasthi, R, Gupta, G, Hsu, A & Hansbro, PM 2019, 'Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems.', Chemico-biological interactions, vol. 299, pp. 168-178.View/Download from: Publisher's site
Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.
Ng, SW, Chan, Y, Chellappan, DK, Madheswaran, T, Zeeshan, F, Chan, YL, Collet, T, Gupta, G, Oliver, BG, Wark, P, Hansbro, N, Hsu, A, Hansbro, PM, Dua, K & Panneerselvam, J 2019, 'Molecular modulators of celastrol as the keystones for its diverse pharmacological activities.', Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 109, pp. 1785-1792.View/Download from: Publisher's site
In the recent years, much attention has been focused on identifying bioactive compounds from medicinal plants that could be employed in therapeutics, which is attributed to their potent pharmacological actions and better toxicological profile. One such example that has come into the light with considerable interest is the pentacyclic triterpenoid, celastrol, which has been found to provide substantial therapeutic properties in a variety of diseases. In an effort to further accelerate its potential to be utilized in clinical practice in the future; along with advancing technologies in the field of drug discovery and development, different researchers have been investigating on the various mechanisms and immunological targets of celastrol that underlie its broad spectrum of pharmacological properties. In this review, we have collated the various research findings related to the molecular modulators responsible for different pharmacological activities shown by celastrol. Our review will be of interest to the herbal, biological, molecular scientist and by providing a quick snapshot about celastrol giving a new direction in the area of herbal drug discovery and development.
Shukla, SD, Shastri, MD, Chong, WC, Dua, K, Budden, KF, Mahmood, MQ, Hansbro, NG, Keely, S, Eri, R, Patel, RP, Peterson, GM & Hansbro, PM 2019, 'Microbiome-focused asthma management strategies.', Current opinion in pharmacology, vol. 46, pp. 143-149.View/Download from: Publisher's site
Asthma is a common, heterogeneous and serious disease with high prevalence globally. Poorly controlled, steroid-resistant asthma is particularly important as there are no effective therapies and it exerts substantial healthcare and societal burden. The role of microbiomes, particularly in chronic diseases has generated considerable interest in recent times. Existing evidence clearly demonstrates an association between asthma initiation and the microbiome, both respiratory and gastro-intestinal, although its' roles are poorly understood when assessing the asthma progression or heterogeneity (i.e. phenotypes/endotypes) across different geographical locations. Moreover, modulating microbiomes could be preventive and/or therapeutic in patients with asthma warrants urgent attention. Here, we review recent advances in assessing the role of microbiomes in asthma and present the challenges associated with the potential therapeutic utility of modifying microbiomes in management.
Soon, L, Ng, PQ, Chellian, J, Madheswaran, T, Panneerselvam, J, Gupta, G, Nammi, S, Hansbro, NG, Hsu, A, Dureja, H, Mehta, M, Satija, S, Hansbro, PM, Dua, K, Collet, T & Chellappan, DK 2019, 'Therapeutic potential of Artemisia vulgaris: An insight into underlying immunological mechanisms.', Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer, vol. 38, no. 3, pp. 205-216.View/Download from: Publisher's site
Artemisia vulgaris is a traditional Chinese herb believed to have a wide range of healing properties; it is traditionally used to treat numerous health ailments. The plant is commonly called mugwort or riverside wormwood. The plant is edible, and in addition to its medicinal properties, it is also used as a culinary herb in Asian cooking in the form of a vegetable or in soup. The plant has garnered the attention of researchers in the past few decades, and several research studies have investigated its biological effects, including antioxidant, anti-inflammatory, anticancer, hypolipidemic, and antimicrobial properties. In this review, various studies on these biological effects are discussed along with the tests conducted, compounds involved, and proposed mechanisms of action. This review will be of interest to the researchers working in the field of herbal medicine, pharmacology, medical sciences, and immunology.
Andrade, LDO, Awasthi, R, Dua, K & Andreoli Pinto, TDJ 2018, 'Matrix-assisted laser desorption ionization–time of flight mass spectrometry for identification of bacteria isolated from pharmaceutical clean rooms', Interventional Medicine and Applied Science, vol. 10, no. 1, pp. 45-53.View/Download from: Publisher's site
© 2018 The Author(s). Introduction: During the manufacturing of sterile drugs, it is of the utmost importance to meet the minimum requirements for asepsis recommended by the legislations on good manufacturing practices-based efficient environmental monitoring. Aims and methods: The availability of relatively simple to use matrix-assisted laser desorption ionization–time of flight mass spectromtomy (MALDI-TOF MS) devices in the last years has changed the laboratory workflows for the microbial identification, mainly in the clinical area. Thus, the objective of this work was to evaluate the suitability of the MALDI-TOF MS technique for the identification of bacteria isolated from the environment of clean rooms used in some stages of the production of a viral vaccine. Eighteen known bacterial species commonly isolated from clean rooms studied were identified by MALDI-TOF technique and by a biochemical technique (BBL Crystal® System). Results: Performance of MALDI-TOF MS was better than biochemical technique for correct species identifications (88.89% and 38.89%, respectively) and produced less unreliable identification (5.55% and 22.22%). Conclusion: MALDI-TOF MS can be implemented for routine identification of bacteria in a pharmaceutical quality control laboratory, but as a database-dependent system, maybe some isolated not identified by this technique must be additionally studied and, if appropriate, added to an in-house database.
Awasthi, R, Rathbone, MJ, Hansbro, PM, Bebawy, M & Dua, K 2018, 'Therapeutic prospects of microRNAs in cancer treatment through nanotechnology.', Drug Delivery and Translational Research, vol. 8, no. 1, pp. 97-110.View/Download from: Publisher's site
MicroRNAs (miRNAs) represent a new class of diagnostic and prognostic biomarker as well as new therapeutic targets in cancer therapy. miRNAs are gaining significant interest due to extensive advancements in knowledge since their discovery and, more recently, their translational application as therapeutic moieties and targets in the management of disease. miRNAs used in the treatment of cancer would position them as a new class of emerging therapeutic agents. Indeed, numerous candidate miRNAs have been identified as having therapeutic application in the treatment of cancer, but there is still much to learn about how to transform these into effective, patient-compliant, and targeted drug delivery systems. In this mini review, we discuss the utility and potential of nanotechnology in miRNA formulation and delivery with particular emphasis on cancer, including their role in conferring multidrug resistance and metastatic capacity. This review benefits both the formulation and biological scientists in understanding and exploring the new vistas of miRNA delivery using nanotechnology in the cancer clinically.
Botelho-Almeida, TDS, Lourenço, FR, Kikuchi, IS, Awasthi, R, Dua, K & Pinto, TDJA 2018, 'Evaluating the Potential, Applicability, and Effectiveness of Ozone Sterilization Process for Medical Devices', Journal of Pharmaceutical Innovation, vol. 13, no. 2, pp. 87-94.View/Download from: Publisher's site
Ozone (O3) can be considered the most potent natural germicide against microorganisms (in vegetative and spore forms) with high efficiency and speed, because of its highly oxidizing activity. Despite this, there are a few studies describing the application of ozone as a sterilizing agent of medical devices. The aim of this communication was to describe the development and validation of a sterilization cycle applied to medical devices.
The sterilization process was challenged using Geobacillus stearothermophilus ATCC 7953 spores, which have shown great resistance. The sterilizing effect of ozone was measured using carriers inoculated with 106 CFU/mL spores, introduced into a 3-mL syringe and lumens of tubes of different sizes and diameters simulating hospital medical products, which have undergone a half-cycle or complete cycle.
The results of sterilization process studied in active vegetative form of microorganisms showed that the ozone sterilization was effective with a bioburden between 105 to 107 CFU/mL with one pulse sterilizing action. The validation of the process was confirmed by the satisfactory results for the half-cycle, corresponding to a treatment with four pulses allowed sterilizing the material with bioburdens < 106 CFU/mL spores which indicate an appropriate sterility assurance level.
The results showed that the ozone may be considered as effective and promising alternative for sterilization of thermosensitive materials and medical devices.
Bugno, A, Saes, DPS, Almodovar, AAB, Dua, K, Awasthi, R, Ghisleni, DDM, Hirota, MT, Oliveira, WAD & Pinto, TDJA 2018, 'Performance Survey and Comparison Between Rapid Sterility Testing Method and Pharmacopoeia Sterility Test', Journal of Pharmaceutical Innovation, vol. 13, no. 1, pp. 27-35.View/Download from: Publisher's site
The sterility test described in pharmacopoeial compendia requires a 14-day incubation period to obtain a valid analytical result. Therefore, the use of alternative methods to evaluate the sterility of pharmaceuticals, such as the BacT/Alert® 3D system, is particularly interesting, because it allows a reduced incubation period and lower associated costs. Considering that the BacT/Alert® 3D system offers several culture media formulations developed for this microbial detection system, the present study was aimed to evaluate and compare the performance of BacT/Alert® 3D with the pharmacopoeial sterility test. There was no significant difference between the ability of the culture media to allow detection of microbial contamination. However, the rapid sterility testing method allowed a more rapid detection of the challenge microorganisms, which indicates that the system is a viable alternative for assessing the sterility of injectable products.
Chellappan, DK, Leng, KH, Jia, LJ, Aziz, NABA, Hoong, WC, Qian, YC, Ling, FY, Wei, GS, Ying, T, Chellian, J, Gupta, G & Dua, K 2018, 'The role of bevacizumab on tumour angiogenesis and in the management of gynaecological cancers: A review.', Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 102, pp. 1127-1144.View/Download from: Publisher's site
OBJECTIVE:The study aims to analyze the effectiveness of bevacizumab in addressing the complications associated with gynecological cancers and evaluates effective treatments for various gynecological cancers. METHODS:The study follows a systematic review approach that has been implemented to analyze the qualitative published data from previous studies. Studies related with the trials of angiogenesis and bevacizumab were selected in the review. RESULTS:In general, the management of gynecological cancers include chemotherapy, surgery and radiation therapy. Results suggest bevacizumab as an effective treatment modality for cervical and several other cancers. Overall, bevacizumab showed promising results in improving the overall survival rate of gynecological cancer patients through the combination of bevacizumab with other chemotherapeutic agents. CONCLUSION:Bevacizumab possess less documented adverse effects when compared to other chemotherapeutic agents. The manifestation and severity of adverse effects reported varied according to the chemotherapeutic agent(s) that were used with bevacizumab in combination therapy. Overall, bevacizumab effectively improved the survival rate in patients with several gynaecological cancers.
Chellappan, DK, Panneerselvam, J, Madheswaran, T, Chellian, J, Ambar Jeet Singh, BJ, Jia Yee, N, Gupta, G & Dua, K 2018, 'Nanogels linked with chitosan: a perspective', MINERVA MEDICA, vol. 109, no. 3, pp. 254-255.View/Download from: Publisher's site
Chellappan, DK, Sivam, NS, Xiang, TK, Pan, LW, Fui, TZ, Kien, C, Nico, K, Yi, FJ, Chellian, J, Cheng, LL, Dahiya, R, Gupta, G, Singhvi, G, Nammi, S, Hansbro, PM & Dua, K 2018, 'Gene therapy and type 1 diabetes mellitus', BIOMEDICINE & PHARMACOTHERAPY, vol. 108, pp. 1188-1200.View/Download from: Publisher's site
Chellappan, DK, Yap, WS, Ahmad Suhaimi, NABT, Gupta, G & Dua, K 2018, 'Current therapies and targets for type 2 diabetes mellitus', PANMINERVA MEDICA, vol. 60, no. 3, pp. 117-131.View/Download from: Publisher's site
Das, P, Kumar, K, Nambiraj, A, Awasthi, R, Dua, K & Malipeddi, H 2018, 'Antibacterial and in vitro growth inhibition study of struvite urinary stones using Oxalis corniculata Linn. leaf extract and its biofabricated silver nanoparticles.', Recent Patents on Drug Delivery and Formulation, vol. 12, no. 3.View/Download from: Publisher's site
Herbal drugs are gaining exponential scientific recognition due to their distinct advantages. In the last 2-3 decades, a gradual increase in worldwide patents on herbal nano-formulations has been noted to address the solubility and bioavailability issues of phytoceuticals. Struvite or ammonium magnesium phosphate hexahydrate (NH4MgPO4.6H2O) is among the important urinary infection stones causing painful urological ailment. These smaller stones may bind together to form a bigger staghorn calculi. Urinary tract infections caused by some gram positive and gram negative bacteria further enhances the chance of formation of such stones. Oxalis corniculata Linn. is an edible plant, traditionally used in the treatment of bacterial infections and kidney stones. However, there is no scientific evidence to relate the use of O. corniculata against struvite kidney stones. Hence, the antibacterial and struvite stones inhibition activity of the aqueous extract of Oxalis corniculata Linn. leaves and its biofabricated silver nanoparticles (AgNPs) was studied.The aqueous extract of O. corniculata was prepared by Soxhlet extraction. AgNPs were synthesized using green technique and were characterized using UV and IR spectroscopy, XRD, TEM, DLS and zeta potential studies. Antibacterial activity of the aqueous extract and the silver nanoparticles were tested against E. coli (gram negative) and S. aureus (gram positive) species. Struvite stones were grown in a gel medium by in vitro single diffusion gel growth technique and its inhibition study was carried out using the extract and its biofabricated nanoparticles..The aqueous extract and its biofabricated AgNPs exhibited potent antibacterial activity against both gram positive and gram negative strains of bacteria. The aqueous extract also effectively repressed the growth of struvite stones and led to the dissolution of stones, but the inhibitory effect was further enhanced by its biofabricated AgNPs.The present work confirms the inhib...
Devi, B, Kumar, Y, Shrivastav, B, Sharma, GN, Gupta, G & Dua, K 2018, 'Current updates on biological and pharmacological activities of doxycycline', PANMINERVA MEDICA, vol. 60, no. 1, pp. 36-39.View/Download from: Publisher's site
Dua, K, Awasthi, R, Madan, JR, Chellappan, DK, Nalluri, BN, Gupta, G, Bebawy, M & Hansbro, PM 2018, 'Novel drug delivery approaches in treating pulmonary fibrosis', Panminerva Medica, vol. 60, no. 4, pp. 238-240.View/Download from: Publisher's site
Dua, K, Awasthi, R, Madan, JR, Chellappan, DK, Nalluri, BN, Gupta, G, Bebawy, M & Hansbro, PM 2018, 'Novel drug delivery approaches in treating pulmonary fibrosis', PANMINERVA MEDICA, vol. 60, no. 4, pp. 238-240.View/Download from: Publisher's site
Dua, K, Chellappan, DK, Singhvi, G, de Jesus Andreoli Pinto, T, Gupta, G & Hansbro, PM 2018, 'Targeting microRNAs using nanotechnology in pulmonary diseases', PANMINERVA MEDICA, vol. 60, no. 4, pp. 230-232.View/Download from: Publisher's site
Dua, K, de Jesus Andreoli Pinto, T, Chellappan, DK, Gupta, G, Bebawy, M & Hansbro, PM 2018, 'Advancements in nano drug delivery systems: a challenge for biofilms in respiratory diseases', PANMINERVA MEDICA, vol. 60, no. 1, pp. 35-36.View/Download from: Publisher's site
Dua, K, Gupta, G, Awasthi, R & Chellappan, DK 2018, 'Why is there an emerging need to look for a suitable drug delivery platform in targeting and regulating microbiota?', PANMINERVA MEDICA, vol. 60, no. 3, pp. 136-137.View/Download from: Publisher's site
Dua, K, Gupta, G, Chellapan, DK, Bebawy, M & Collet, T 2018, 'Nanoparticle-based therapies as a modality in treating wounds and preventing biofilm', PANMINERVA MEDICA, vol. 60, no. 4, pp. 237-238.View/Download from: Publisher's site
Dua, K, Gupta, G, Koteswararao, N & Bebawy, M 2018, 'Nano-antibiotics: a novel approach in treating P. aeruginosa biofilm infections', MINERVA MEDICA, vol. 109, no. 5, pp. 400-401.View/Download from: Publisher's site
Dua, K, Krishna, RV, Shukla, SD, Singhvi, G, Shastri, MD, Chellappan, DK, Satija, S, Mehta, M, Gulati, M, Pinto, TDJA, Gupta, G & Hansbro, PM 2018, 'Multi-drug resistant Mycobacterium tuberculosis & oxidative stress complexity: Emerging need for novel drug delivery approaches', BIOMEDICINE & PHARMACOTHERAPY, vol. 107, pp. 1218-1229.View/Download from: Publisher's site
Dua, K, Madan, JR, Chellappan, DK & Gupta, G 2018, 'Nanotechnology in drug delivery gaining new perspectives in respiratory diseases', PANMINERVA MEDICA, vol. 60, no. 3, pp. 135-136.View/Download from: Publisher's site
G, G, R, D, M, S, J, T, SK, S, M, A, G, K & K, D 2018, 'ROLE OF LIRAGLUTIDE IN A MAJOR COMPLICATION OF DIABETES: A CRITICAL REVIEW OF CLINICAL STUDIES', Bulletin of Pharmaceutical Research, vol. 8, no. 1.View/Download from: Publisher's site
Gupta, G, Bebawy, M, Andreoli Pinto, TDJ, Chellappan, DK, Mishra, A & Dua, K 2018, 'Role of the Tristetraprolin (Zinc Finger Protein 36 Homolog) Gene in Cancer', CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, vol. 28, no. 3, pp. 217-221.View/Download from: Publisher's site
Gupta, G, Chellappan, DK, de Jesus Andreoli Pinto, T, Hansbro, PM, Bebawy, M & Dua, K 2018, 'Tumor suppressor role of miR-503.', Panminerva medica, vol. 60, no. 1, pp. 17-24.View/Download from: Publisher's site
MicroRNAs (miRNAs) are non-coding RNAs of around 20-25 nucleotides in length with highly conserved characteristics. They moderate post-transcriptional silencing by precisely combining with 3' untranslated regions (UTRs) of target mRNAs at a complementary site. miR‑503, an associate of the "canonical" miRNA-16 family, is expressed in numerous types of tumors such as breast cancer, prostate cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioblastoma and several others. There is convincing evidence to show that miR‑503 functions as a tumor suppressor gene through its effects on target genes that regulate cell proliferation, migration, and invasion in tumor cells. In this current assessment, we discuss the biology and tumor suppressor role of miR‑503 in different cancers and elaborate on its mechanism of action.
Gupta, G, de Jesus Andreoli Pinto, T, Chellappan, DK, Mishra, A, Malipeddi, H & Dua, K 2018, 'A clinical update on metformin and lung cancer in diabetic patients.', Panminerva medica, vol. 60, no. 2, pp. 70-75.View/Download from: Publisher's site
Diabetes mellitus (DM) is frequently increased in many countries and become a serious health problem worldwide. Diabetes is associated with dysfunction of different organs such as heart, eyes, blood vessels, nerves, and kidneys. There is a strong connection between diabetes and cancer. Metformin is one of the most commonly prescribed oral antidiabetic medicines and it is suggested as the first-line therapy due to its comparatively safe, inexpensive, effective and well-tolerated. Some of the in vitro and in vivo investigations proved that metformin may have a direct anticancer action by preventing the proliferation of malignant cells and formations of the colony, inducing arrest of cell cycle and apoptosis and suppressing tumor growth. The antiproliferative mechanism of metformin alone or in combination with various chemotherapeutic agents is complex and involves several beneficial roles. In this regard, clinical studies are required to explain these roles. In the coming future, the use of metformin, alone or in combination with current chemotherapy, might be a conventional approach to effectually manage lung cancer. This mini-review provides a critical overview of currently available clinical trials investigating the effects of metformin in lung cancer.
Gupta, G, Sharma, RK, Dahiya, R, Mishra, A, Tiwari, J, Sharma, GN, Sharma, S & Dua, K 2018, 'Aphrodisiac Activity of an Aqueous Extract o f Wood Ear Mushroom, Auricularia polytricha (Heterobasidiomycetes), in Male Rats', INTERNATIONAL JOURNAL OF MEDICINAL MUSHROOMS, vol. 20, no. 1, pp. 81-88.View/Download from: Publisher's site
Gupta, G, Singhvi, G, Chellappan, DK, Sharma, S, Mishra, A, Dahiya, R, de Jesus Andreoli Pinto, T & Dua, K 2018, 'Peroxisome proliferator-activated receptor gamma: promising target in glioblastoma.', Panminerva medica, vol. 60, no. 3, pp. 109-116.View/Download from: Publisher's site
Glioblastoma, also known as glioblastoma multiforme, is the most common and worldwide-spread cancer that begins within the brain. Glioblastomas represent 15% of brain tumors. The most common length of survival following diagnosis is 12 to 14 months with less than 3% to 5% of people surviving longer than five years. Without treatment, survival is typically 3 months. Among all receptors, special attention has been focused on the role of peroxisome proliferator-activated receptors (PPARs) in glioblastoma. PPARs are ligand-activated intracellular transcription factors. The PPAR subfamily consists of three subtypes encoded by distinct genes named PPARα, PPARβ/δ, and PPARγ. PPARγ is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPARγ agonists, a group of anti-diabetics, thiazolidinedione drugs, have an increased median survival for glioblastoma. In this paper, the recent progresses in understanding the potential mechanism of PPARγ in glioblastoma are summarized.
Gupta, G, Tiwari, J, Dahiya, R, Sharma, RK, Mishra, A & Dua, K 2018, 'RECENT UPDATES ON NEUROPHARMACOLOGICAL EFFECTS OF LUTEOLIN', EXCLI JOURNAL, vol. 17, pp. 211-214.View/Download from: Publisher's site
Madan, JR, Dagade, RH, Awasthi, R & Dua, K 2018, 'Formulation and solid state characterization of carboxylic acid-based co-crystals of tinidazole: An approach to enhance solubility.', Polimery w medycynie, vol. 48, no. 2, pp. 99-104.View/Download from: Publisher's site
BACKGROUND:Tinidazole (TNZ) is an anti-parasite drug used in the treatment of a variety of amebic and parasitic infections. It has low solubility in aqueous media and is categorized under Class II of the Biopharmaceutical Classification System. OBJECTIVES:The aim of this research was to study the potential for enhancing the solubility of TNZ using carboxylic acid co-crystals. MATERIAL AND METHODS:The solubility of TNZ was determined individually using 6 carboxylic acids for forming co-crystals at a 1:1 stoichiometric ratio. Three carboxylic acids - namely tartaric acid (TA), oxalic acid (OA) and glutaric acid (GA) - resulted in the formation of co-crystals with enhanced solubility. An equilibrium solubility study of TNZ co-crystals at 1:1.5 and 1:2 stoichiometric ratios was also carried out. The co-crystals which developed were evaluated using X-ray powder diffraction (XRD) and differential scanning calorimetry (DSC) to study the drug-co-crystal former interactions. RESULTS:The solubility of TNZ in distilled water was found to be 0.014 mg/mL. The highest enhancement ratio was obtained with TNZ and TA at a ratio of 1:1. Differential scanning calorimetry thermograms suggested that the drug and carboxylic acids had undergone interactions such as hydrogen bonding. The XRD and DSC results confirmed the formation of co-crystals. CONCLUSIONS:It was concluded that the results of enhanced solubility of TNZ using co-crystals is a clear indication of the potential for co-crystals to be used in the future for other poorly water-soluble drugs, considering that co-crystals are a safe and cost-effective approach.
Madan, JR, Patil, S, Mathure, D, Bahirat, SP, Awasthi, R & Dua, K 2018, 'Improving dissolution profile of poorly water-soluble drug using non-ordered mesoporous silica', Marmara Pharmaceutical Journal, vol. 22, no. 2, pp. 249-258.View/Download from: Publisher's site
© 2018 Marmara University Press. The aim of the study was to increase dissolution rate of atorvastatin by the use of mesoporous silica SYLOID® 244 FP. The poorly soluble drug atorvastatin was adsorbed on and/or into SYLOID® 244 FP in the ratios 1:1, 1:1.1.5, 1:2, 1:2.5, 1:3 and 1:3.5 via a wetness impregnation method. The absence of crystalline form and presence of hydrogen bond interaction between atorvastatin and SYLOID® 244 FP is done by Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The atorvastatin loaded matrix lacked in the crystalline form of atorvastatin and it showed improvement in the dissolution rate of ATC. The flowability of the atorvastatin loaded matrix powder was evaluated by bulk density, Carr's index and angle of repose. This matrix was then processed into a tablet by direct compression method. A 32 full factorial design was applied to investigate the combined effect of two formulation variables - volume of ethanol and amount of SYLOID® 244 FP. The tablets were evaluated for hardness, friability, drug content and drug dissolution studies. The solubility of atorvastatin-loaded matrix was increased up to 4.28 times. Atorvastatin tablet prepared from drug-loaded silica may provide a feasible approach for development of an oral formulation for this poorly water-soluble drug.
Madan, JR, Pawar, AR, Patil, RB, Awasthi, R & Dua, K 2018, 'Preparation, characterization and in vitro evaluation of tablets containing microwave-assisted solid dispersions of apremilast.', Polimery w medycynie, vol. 48, no. 1, pp. 17-24.View/Download from: Publisher's site
BACKGROUND:Solid dispersions are among the techniques successfully employed to enhance the dissolution of poorly water-soluble drugs. Microwave (MW)-assisted evaporative crystallization has been used to prepare solid dispersions of drugs and polymers. OBJECTIVES:The aim of the study was to investigate the solubility of apremilast (APM) in water by exploring the effect of MW-assisted solid dispersion technology. MATERIAL AND METHODS:In the present study, solid dispersions of APM, a poorly water-soluble drug, were prepared. The solid dispersions were prepared using the conventional method (CM) and the MW-based solvent evaporation technique. Microwave energy was used to enhance the solubility and dissolution rate of APM. The physical mixture and solid dispersions were characterized using Fourier-transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Apremilast tablets containing MW-assisted solid dispersions were prepared by the direct compression technique and compared with the marketed formulation (Aprezo tablets). RESULTS:The results obtained confirmed the conversion of crystalline APM to an amorphous form. The XRPD pattern of the MW-assisted formulation at a 2:1 ratio suggests the amorphous structure of APM within the formulation. Based on solubility studies results, Syloid® 244FP was selected as the best carrier. The dissolution study results suggested that the APM tablet prepared using MW-assisted solid dispersions at a 2:1 carrier/drug ratio improved the APM dissolution rate compared to the marketed formulation. CONCLUSIONS:Based on the results, it can be concluded that the MW-assisted solid dispersion technique may be an effective approach to enhancing the dissolution profile of other poorly water-soluble drugs.
Mathure, D, R Madan, J, N Gujar, K, Tupsamundre, A, A Ranpise, H & Dua, K 2018, 'Formulation and Evaluation of Niosomal in situ Nasal Gel of a Serotonin Receptor Agonist, Buspirone Hydrochloride for the Brain Delivery via Intranasal Route.', Pharmaceutical Nanotechnology, vol. 6, no. 1, pp. 69-78.View/Download from: Publisher's site
Buspirone Hydrochloride is an anxiolytic agent and serotonin receptor agonist belonging to azaspirodecanedione class of compounds used in the treatment of anxiety disorders. It has short half-life (2-3h) and low oral bioavailability (4%) due to extensive first pass metabolism.The nasal mucosa has several advantages viz., large surface area, porous endothelial membrane, high blood flow, avoidance of first-pass metabolism and ready accessibility that lead to faster and higher drug absorption. Keeping these facts in mind, the objective of the present study was to develop Buspirone hydrochloride loaded niosomal in-situ nasal gel.Buspirone hydrochloride niosomal in situ nasal gel was formulated, optimized and evaluated with the objective to deliver drug to the brain via intranasal route. Niosomes were prepared by thin film evaporation method and optimized using32 factorial design. Niosomes were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. Buspirone hydrochloride loaded niosomes were further incorporated into Carbopol 934P and HPMC K4M liquid gelling system for the formation of in situ gel. The resultant solution was assessed for various parameters, viz., gelling time, gelling capacity, viscosity at pH 5 and pH 6.The vesicle size of all niosomal suspension batches ranges between 168.3 -310.5 nm. The vesicle size of optimized niosomal suspension F5 batch is 181.9±0.36nm. For F5 batch, the value of zeta potential was found to be -15.4 mV; this specifies that prepared niosomes have sufficient surface charge to prevent aggregation of the vesicles. % entrapment efficiency for all batches was found in the range 72.44±0.18% to 87.7±0.66%. The cumulative percent release of niosomal suspension ranges from 66.34±0.39 to 84.26±0.26%. Ex vivo permeation of Buspirone hydrochloride through the sheep nasal mucosa showed that 83.49% w/w drug permeated after 8 h. The SEM and Zeta potential studies showed the formation of stable vesic...
Ranpise, HA, Gujar, KN, Mathure, D, Satpute, PP, Awasthi, R, Dua, K & Madan, JR 2018, 'Skin targeting of oxiconazole nitrate loaded nanostructured lipid carrier gel for fungal infections.', Pharmaceutical Nanotechnology, vol. 6, no. 3, pp. 192-200.View/Download from: Publisher's site
The progression of fungal infections can be rapid and serious due to compromising with immune function. They may cause liver damage, affect estrogen levels or may cause allergic reactions. Oxyconazole nitrate (OCXN) is a broad spectrum commonly used antifungal drug. It acts by erogosterol biosynthesis inhibition, which causes lysis of fungal cell membrane because of changes in both membrane integrity and fluidity and direct membrane damage of fungal cells. However, its poor water solubility and short half-life (3-5 h) limit its applications. This study aimed to develop and evaluate OXZN-loaded nanostructured lipid carrier (NLC) to improve its solubility and prolong its release for the treatment of fungal infection via topical administration. OXZN-NLC was prepared by ultrasonication method using 32 full factorial design. Glyceryl monostearate (GMS) (X1) and oleic acid (X2) were used as independent variables and particle size (PS) and percentage entrapment efficiency (% EE) as dependent variables. The OXZN NLCs were characterized for particle size, particle morphology and entrapment efficiency. The mean diameter of optimized OXZN-NLCs was found to be 124 ± 2 nm. Spherical shape and size were confirmed using scanning electron microscopy (SEM). Skin deposition study showed about 82.74% deposition as compared with the marketed formulation that showed 68.42% deposition. The developed NLCs show a sustained release pattern and high drug disposition in the infected area. Hence, OXZN-NLC could be a potential alternative for the treatment of topical fungal infection after clinical evaluation in near future.
Rapalli, VK, Singhvi, G, Dubey, SK, Gupta, G, Chellappan, DK & Dua, K 2018, 'Emerging landscape in psoriasis management: From topical application to targeting biomolecules.', Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 106, pp. 707-713.View/Download from: Publisher's site
Psoriasis is a chronic autoimmune skin disorder affecting 2-3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.
Samvedna, S, Jindal, S, Mishra, G, Madan, JR, Gupta, G, Awasthi, R, Pinto, TDJA, Dua, K & Kulkarni, GT 2018, 'Formulation and characterization of oral rapid disintegrating tablets of levocetirizine.', Polimery w medycynie, vol. 48, no. 1, pp. 31-40.View/Download from: Publisher's site
BACKGROUND:Levocetirizine, active R (-) enantiomer of cetirizine, is an orally active and selective H1 receptor antagonist used medically as an anti-allergic. Allergic rhinitis is a symptomatic disorder of the nose induced by inflammation mediated by immunoglobulin E (IgE) in the membrane lining the nose after allergen exposure. OBJECTIVES:The purpose of the present study was to prepare rapidly disintegrating tablets of levocetirizine after its complexation with β-cyclodextrin (β-CD). MATERIAL AND METHODS:Levocetirizine-β-CD complex tablets were prepared by direct compression technique using 3 synthetic superdisintegrants in different proportions. Development of the formulation in the present study was mainly based on the concentration of superdisintegrants and the properties of the drug. Nine batches of tablets were formulated and evaluated for various parameters: drug content, weight variation, water absorption ratio, wetting time, in vitro disintegration, hardness, friability, thickness uniformity, and in vitro dissolution. RESULTS:A Fourier-transform infrared spectroscopy (FTIR) study showed that there were no significant interactions between the drug and the excipients. The prepared tablets were good in appearance and showed acceptable results for hardness and friability. The in vitro disintegrating time of the formulated tablet batches was found to be 15-35 s percentage and the drug content of tablets in all formulations was found to be between 90-102%, which complied with the limits established in the United States Pharmacopeia. CONCLUSIONS:Complexation of levocetirizine with β-CD significantly improves the solubility of the drug. The disintegration time of the tablets was decreased with an increase in superdisintegrant amount. The tablets (batch CPX5) had a minimum disintegration time of 20 s and 99.99% of the drug was released within 10 min.
Shastri, MD, Shukla, SD, Chong, WC, Dua, K, Peterson, GM, Patel, RP, Hansbro, PM, Eri, R & O'Toole, RF 2018, 'Role of Oxidative Stress in the Pathology and Management of Human Tuberculosis', OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, vol. 2018.View/Download from: Publisher's site
Singh, Y, Gupta, G, Sharma, R, Matta, Y, Mishra, A, Andreoli Pinto, TDJ & Dua, K 2018, 'Embarking Effect of ACE2-Angiotensin 1-7/Mas Receptor Axis in Benign Prostate Hyperplasia', CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, vol. 28, no. 2, pp. 115-124.View/Download from: Publisher's site
Singhvi, G, Girdhar, V, Patil, S, Gupta, G, Hansbro, PM & Dua, K 2018, 'Microbiome as therapeutics in vesicular delivery.', Biomedicine and Pharmacotherapy, vol. 104, pp. 738-741.View/Download from: Publisher's site
Microbiome refers to an ecological community of various symbiotic and pathogenic microorganisms, which plays a crucial role in human health and disease. The concept of novel drug delivery systems particularly the vesicular drug delivery systems is gaining massive attention. This emerging technology has started expanding its horizons in the area of microbiome delivery. This mini-review highlights the role of vesicular systems such as nanoparticles, liposomes etc. as a host/carrier for the microbiome in targeting various diseases. This review will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of vesicular delivery system as carrier for microbiome delivery.
Singhvi, G, Manchanda, P, Rapalli, VK, Dubey, SK, Gupta, G & Dua, K 2018, 'MicroRNAs as biological regulators in skin disorders', BIOMEDICINE & PHARMACOTHERAPY, vol. 108, pp. 996-1004.View/Download from: Publisher's site
Singhvi, G, Patil, S, Girdhar, V, Chellappan, DK, Gupta, G & Dua, K 2018, '3D-printing: an emerging and a revolutionary technology in pharmaceuticals', PANMINERVA MEDICA, vol. 60, no. 4, pp. 170-173.View/Download from: Publisher's site
Sunkara, KP, Gupta, G, Hansbro, PM, Dua, K & Bebawy, M 2018, 'Functional relevance of SATB1 in immune regulation and tumorigenesis.', Biomedicine and Pharmacotherapy, vol. 104, pp. 87-93.View/Download from: Publisher's site
The Special AT-rich Sequence Binding Protein 1 (SATB1) is a chromatin organiser and transcription factor which regulates numerous cellular processes such as differentiation, proliferation and apoptosis through effects on gene expression. SATB1 undergoes various post-translational modifications, which determine its interaction with co-activators and co-repressors to induce regulation of gene transcription. SATB1 is an identified oncogene, its increased expression is associated with poor prognosis in many cancers. This paper provides a review on SATB1-mediated immune responses and on its target genes in the context of tumorigenesis and tumour progression. Specifically, we discuss the role of SATB1 in tumour immunity, Epithelial to Mesenchymal Transition (EMT), metastasis and multidrug resistance. Therapeutic targeting of aberrant SATB1 may be an important strategy in the treatment of cancer.
Sureka, S, Gupta, G, Agarwal, M, Mishra, A, K Singh, S, P Singh, R, Sah, SK, de Jesus A Pinto, T & Dua, K 2018, 'Formulation, In-Vitro and Ex-Vivo Evaluation of Tretinoin Loaded Cubosomal Gel for the Treatment of Acne.', Recent Patents on Drug Delivery and Formulation, vol. 12, no. 2, pp. 121-129.View/Download from: Publisher's site
The current work was attempted to formulate and evaluate the topical sustained release delivery systems called cubosomes containing Tretinoin for the acne treatment. The recent patents on various formulations of tretinoin (EP0408370A2) helped in selecting a new formulation and evaluation.Tretinoin loaded cubosomes were prepared by bottom-up technique, using varying the concentration of lipid and surfactant and keeping the drug concentration constant, a total of nine formulations of tretinoin was developed. These preparations were evaluated for surface charge, particle size, particle morphology, encapsulation efficiency, in-vivo and in-vitro release studies of gel enriched with cubosome dispersion. Finally, the stability studies of cubosomal gel were performed on optimized formulations.Significant result were obtained with tretinoin formulation as the drug is lipophilic, so it gives more depot effect on the epidermis and good retention property. The data obtained from the formulations showed that formulation TCF-5 was the optimized formulation which exhibited better drug release and entrapment efficiency.It can be concluded that cubosomes offer benefits of quick onset as well as the maximal release of drug with fewer side effects. Thus, cubosomes represent a capable transporter having the property to sustain the release of drug, potential to localize the drug in the skin with a possible clinical application for acne vulgaris treatment due to cubosome depot effect on the epidermis.
Tiwari, J, Gupta, G, de Jesus Andreoli Pinto, T, Sharma, R, Pabreja, K, Matta, Y, Arora, N, Mishra, A, Sharma, R & Dua, K 2018, 'Role of microRNAs (miRNAs) in the pathophysiology of diabetes mellitus.', Panminerva medica, vol. 60, no. 1, pp. 25-28.View/Download from: Publisher's site
Diabetes mellitus is becoming the critical problem among the entire world and it is difficult to understand the molecular mechanism representing the concept of diabetic pathology. Recently the knowledge of the involvement of genetics in type 2 diabetes mellitus (T2DM) susceptibility has sketched a great concentration towards the transcriptional activity of β cells within the pancreas. This disease becomes the leading cause of death, so it is necessary to study the molecular pathogenesis, phenotypes, and characteristics to design the therapeutic parameters. Here in this review role of miRNA is being illustrated as it plays a crucial role in the pathogenesis, progression, and fate of beta cells of pancreas regulating the insulin secretion. Here in this review, we try to include the effects and pathophysiology of various miRNA in diabetes mellitus and on the various sites of the human body.
Chellappan, DK, Ng, ZY, Wong, J-Y, Hsu, A, Wark, P, Hansbro, N, Taylor, J, Panneerselvam, J, Madheswaran, T, Gupta, G, Bebawy, M, Hansbro, PM & Dua, K 2018, 'Immunological axis of curcumin-loaded vesicular drug delivery systems.', Future medicinal chemistry, vol. 10, no. 8, pp. 839-844.View/Download from: Publisher's site
Several vesicular systems loaded with curcumin have found their way in the therapeutic applications of several diseases, primarily acting through their immunological pathways. Such systems use particles at a nanoscale range, bringing about their intended use through a range of complex mechanisms. Apart from delivering drug substances into target tissues, these vesicular systems also effectively overcome problems like insolubility and unequal drug distribution. Several mechanisms are explored lately by different workers, and interest over vesicular curcumin has been renewed in the past decade. This commentary discusses several immunological targets in which curcumin is employed in a vesicular form.
Dua, K, Hansbro, NG, Foster, PS & Hansbro, PM 2018, 'Targeting MicroRNAs: Promising Future Therapeutics in the Treatment of Allergic Airway Disease', CRITICAL REVIEWS IN EUKARYOTIC GENE EXPRESSION, vol. 28, no. 2, pp. 125-127.View/Download from: Publisher's site
Ng, ZY, Wong, J-Y, Panneerselvam, J, Madheswaran, T, Kumar, P, Pillay, V, Hsu, A, Hansbro, N, Bebawy, M, Wark, P, Hansbro, P, Dua, K & Chellappan, DK 2018, 'Assessing the potential of liposomes loaded with curcumin as a therapeutic intervention in asthma', COLLOIDS AND SURFACES B-BIOINTERFACES, vol. 172, pp. 51-59.View/Download from: Publisher's site
Awasthi, R, Roseblade, A, Hansbro, PM, Rathbone, MJ, Dua, K & Bebawy, M 2018, 'Nanoparticles in Cancer Treatment: Opportunities and Obstacles', CURRENT DRUG TARGETS, vol. 19, no. 14, pp. 1696-1709.View/Download from: Publisher's site
Awasthi, R, Kulkarni, GT, Ramana, MV, de Jesus Andreoli Pinto, T, Kikuchi, IS, Molim Ghisleni, DD, de Souza Braga, M, De Bank, P & Dua, K 2017, 'Dual crosslinked pectin-alginate network as sustained release hydrophilic matrix for repaglinide.', International journal of biological macromolecules, vol. 97, pp. 721-732.View/Download from: Publisher's site
Repaglinide, an oral antidiabetic agent, has a rapid onset of action and short half-life of approximately 1h. Developing a controlled and prolonged release delivery system is required to maintain its therapeutic plasma concentration and to eliminate its adverse effects particularly hypoglycemia. The present study aimed to develop controlled release repaglinide loaded beads using sodium alginate and pectin with dual cross-linking for effective control of drug release. The prepared beads were characterized for size, percentage drug entrapment efficiency, in vitro drug release and the morphological examination using scanning electron microscope. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin® tablets 2mg, Novo Nordisk) was determined by the same procedure as followed for beads. The particle size of beads was in the range of 698±2.34-769±1.43μm. The drug entrapment efficiency varied between 55.24±4.61 to 82.29±3.42%. The FTIR results suggest that there was no interaction between repaglinide and excipients. The XRD and DSC results suggest partial molecular dispersion and amorphization of the drug throughout the system. These results suggest that repaglinide did not dissolve completely in the polymer composition and seems not to be involved in the cross-linking reaction. The percent drug release was decreased with higher polymer concentrations. In conclusion, the developed beads could enhance drug entrapment efficiency, prolong the drug release and enhance bioavailability for better control of diabetes.
Azeran, NSB, Zazali, NDB, Timur, SS, Ozdogan, AI, Ekizoglu, M, Sheshala, R, Dua, K, Sahu, PS & Senel, S 2017, 'Moxifloxacin Loaded Chitosan Gel Formulations for the Treatment of Periodontal Diseases', JOURNAL OF POLYMER MATERIALS, vol. 34, no. 1, pp. 157-169.
Chellappan, DK, Hansbro, PM, Dua, K, Hsu, A, Gupta, G, Ng, ZY, Wong, J-Y, Chellian, J & Panneerselvam, J 2017, 'Vesicular Systems Containing Curcumin and Their Applications in Respiratory Disorders - A Mini Review.', Pharmaceutical Nanotechnology, vol. 5, no. 4, pp. 250-254.View/Download from: Publisher's site
Vesicular systems like nanotechnology and liposomes are gaining tremendous attention lately in the field of respiratory diseases. These formulations enhance bioavailability of the drug candidate, which could be achieved through a novel drug delivery mechanism. Moreover, the therapeutic potential achieved through these systems is highly controllable over long durations of time providing better efficacy and patient compliance.The objective of this paper is to review the recent literature on vesicular drug delivery systems containing curcumin.We have collated and summarized various recent attempts made to develop different controlled release drug delivery systems containing curcumin which would be of great interest for herbal, formulation and biological scientists. There are several vesicular nanotechnological techniques involving curcumin which have been studied recently, targeting pulmonary diseases.Different vesicular systems containing curcumin are being studied for their therapeutic potential in different respiratory diseases. There has been a renewed interest in formulations containing curcumin recently, primarily owing to the broad spectrum therapeutic potential of this miracle substance. Various types of formulations, containing curcumin, targeting different bodily systems have recently emerged and, nevertheless, the search for newer frontiers with this drug goes on.This mini review, in this direction, tries to highlight the key research interventions employing vesicular systems of drug delivery with curcumin.
Das, P, Gupta, G, Velu, V, Awasthi, R, Dua, K & Malipeddi, H 2017, 'Formation of struvite urinary stones and approaches towards the inhibition-A review.', Biomedicine and Pharmacotherapy, vol. 96, pp. 361-370.View/Download from: Publisher's site
Struvite is one of the most common urinary/kidney stones, composed of magnesium ammonium phosphate (MgNHPO4·H2O). They are also termed as infection stones as these are associated with urinary tract infections. Numerous studies have been carried out to examine the growth and inhibition of struvite stones.This review summarizes various reports on the factors responsible for inducing struvite stones in the kidney and gives a detailed account of studies on inhibition of growth of struvite crystals.The presence of urea-splitting bacteria such as Proteus mirabilis and alkaline pH plays a crucial role in struvite formation. In vitro inhibition of struvite stones by various chemical agents were examined mainly in artificial urine whereas inhibition by herbal extracts was studied in vitro by gel diffusion technique. Herbal extracts of curcumin, Boerhaavia diffusa Linn, Rotula aquatica and many other plants, as well as some chemicals like pyrophosphate, acetohydroxamic acid, disodium EDTA and trisodium citrate, were reported to successfully inhibit struvite formation.The present review recapitulates various factors affecting the growth of struvite urinary stones and the inhibitory role of certain chemicals and herbal extracts. Most of the tested plants are edible hence can be easily consumed without any adverse effects whereas the side effects of chemicals are unknown due to lack of toxicity studies. Thus, the use of herbal extracts might serve as an alternate and safe therapy for prevention of struvite stones.
Das, P, Kumar, K, Nambiraj, A, Rajan, R, Awasthi, R, Dua, K & Himaja, M 2017, 'Potential therapeutic activity of Phlogacanthus thyrsiformis Hardow (Mabb) flower extract and its biofabricated silver nanoparticles against chemically induced urolithiasis in male Wistar rats', INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES, vol. 103, pp. 621-629.View/Download from: Publisher's site
Dua, K, Bebawy, M, Awasthi, R, Tekade, RK, Tekade, M, Gupta, G, De Jesus Andreoli Pinto, T & Hansbro, PM 2017, 'Application of Chitosan and its Derivatives in Nanocarrier Based Pulmonary Drug Delivery Systems.', Pharmaceutical Nanotechnology, vol. 5, no. 4, pp. 243-249.View/Download from: Publisher's site
The respiratory tract as a non-invasive route of drug administration is gaining increasing attention in the present time on achieving both local and the systemic therapeutic effects. Success in achieving pulmonary delivery, requires overcoming barriers including mucociliary clearance and uptake by macrophages. An effective drug delivery system delivers the therapeutically active moieties at the right time and rate to target sites. A major limitation associated with most of the currently available conventional and controlled release drug delivery devices is that not all the drug candidates are well absorbed uniformly locally or systemically.We searched and reviewed the literature focusing on chitosan and chitosan derivative based nanocarrier systems used in pulmonary drug delivery. We focused on the applications of chitosan in the development of nanoparticles for this purpose.Chitosan, a natural linear bio-polyaminosaccharide is central in the development of novel drug delivery systems (NDDS) including nanoparticles for use in the treatment of various respiratory diseases. It achieves this through its unique properties of biodegradability, biocompatibility, mucoadhesivity and its ability to enhance macromolecule permeation across membranes. It also achieves sustained and targeted effects, primary requirements for an effective pulmonary drug delivery system. This review highlights the applications and importance of chitosan with special emphasis on nanotechnology, employed in the management of respiratory diseases such as asthma, Chronic Obstructive Pulmonary Disease (COPD), lung cancer and pulmonary fibrosis.This review will be of interest to both the biological and formulation scientists as it provides a summary on the utility of chitosan in pulmonary drug delivery systems. At present, there are no patented chitosan based controlled release products available for pulmonary drug delivery and so this area has enormous potential in the field of respiratory science.
Dua, K, Shukla, SD & Hansbro, PM 2017, 'Aspiration techniques for bronchoalveolar lavage in translational respiratory research: Paving the way to develop novel therapeutic moieties.', Journal of biological methods, vol. 4, no. 3, p. e73.View/Download from: Publisher's site
Bronchoalveolar lavage (BAL) is a simple, yet informative tool in understanding the immunopathology of various lung diseases via quantifying various inflammatory cells, cytokines and growth factors. At present, this traditional method is often blended with several robust and sophisticated molecular and biological techniques sustaining the significance and longevity of this technique. Crucially, the existence of slightly distinct approaches and variables employed at different laboratories around the globe in performing BAL aspiration indeed demands an utmost need to optimize and develop an effective, cost-effective and a reproducible technique. This mini review will be of importance to the biological translational scientist, particularly respiratory researchers in understanding the fundamentals and approaches to apply and consider with BAL aspiration techniques. This will ensure generating a meaningful and clinically relevant data which in turn accelerate the development of new and effective therapeutic moieties for major respiratory conditions.
Dua, K, Shukla, SD, Pinto, TDJA & Hansbro, PM 2017, 'Nanotechnology: Advancing the translational respiratory research', Interventional Medicine and Applied Science, vol. 9, no. 1, pp. 39-41.View/Download from: Publisher's site
© 2017 The Author(s). Considering the various limitations associated with the conventional dosage forms, nanotechnology is gaining increased attention in drug delivery particularly in respiratory medicine and research because of its advantages like targeting effects, improved pharmacotherapy, and patient compliance. This paper provides a quick snapshot about the recent trends and applications of nanotechnology to various translational and formulation scientists working on various respiratory diseases, which can help paving a new path in developing effective drug delivery system.
Dua, K, Shukla, SD, Tekade, RK & Hansbro, PM 2017, 'Whether a novel drug delivery system can overcome the problem of biofilms in respiratory diseases?', Drug Delivery and Translational Research, vol. 7, no. 1, pp. 179-187.View/Download from: Publisher's site
Biofilm comprises a community of microorganisms which form on medical devices and can lead to various threatening infections. It is a major concern in various respiratory diseases like cystic fibrosis, chronic obstructive pulmonary disease, etc. The treatment strategies for such infections are difficult due to the resistance of the microflora existing in the biofilms against various antimicrobial agents, thus posing threats to the patient population. The present era witnesses the beginning of research to understand the biofilm physiology and the associated microfloral diversity by applying -omics approaches. There is very limited information about how the deposition of biofilm on the respiratory devices and lung itself affects the drug delivered, the delivery system, and other implications. The present mini review summarizes the basic introduction to the biofilms and its avoidance using various drug delivery systems with special emphasis on the respiratory diseases. Understanding the approaches, principles, and modes of drug delivery involved in preventing biofilm deposition will be of interest to both biological and formulation scientists, thereby opening avenues to explore the new vistas in biofilm research for identifying better treatments for pulmonary infectious diseases.
Gupta, G, Chellappan, DK, Agarwal, M, Ashwathanarayana, M, Nammi, S, Pabreja, K & Dua, K 2017, 'Pharmacological evaluation of the recuperative effect of morusin against aluminium trichloride (AlCl 3 )-induced memory impairment in rats', Central Nervous System Agents in Medicinal Chemistry, vol. 17, no. 3, pp. 196-200.View/Download from: Publisher's site
© 2017 Bentham Science Publishers. Background: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl 3 )-induced memory impairment in rats along with biochemical mechanism of its protective action. Methods: Memory deficiency was produced by AlCl 3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels. Results: AlCl 3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl 3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl 3 -induced learning and memory shortages along with diminution of AlCl 3 -induced rise in brain AChE activity and brain oxidative stress levels. Conclusion: It may be concluded that morusin exerts a memory-preservative outcome in mental discrepancies of rats feasibly through its various activities.
Gupta, G, Chellappan, DK, Kikuchi, IS, Pinto, TDJA, Pabreja, K, Agrawal, M, Singh, Y, Tiwari, J & Dua, K 2017, 'Nephrotoxicity in Rats Exposed to Paracetamol: The Protective Role of Moralbosteroid, a Steroidal Glycoside.', Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer, vol. 36, no. 2, pp. 113-119.View/Download from: Publisher's site
Paracetamol (PCM) has an acceptable safety profile when used at prescribed doses. However, it is now understood that paracetamol can damage the kidneys when administered as an overdose. In addition, oxidative stress can play a major role in causing nephrotoxicity. This investigation studies the efficacy of moralbosteroid isolated from M. alba stem bark. Nephrotoxicity was induced with administration of paracetamol. Nephroprotection was studied using two doses of the extract. The experimental animals were divided into four groups (n = 6). Two groups served as positive and negative controls, respectively, and two received the test substances. All of the contents were orally administered. Significant reductions in nephrotoxicity and oxidative damages were observed in the treatment groups. There was a marked decrease in blood levels of urea, creatinine, and lipid peroxidation. Furthermore, it was found that glutathione levels in the blood increased dramatically after treatment. Histological findings confirmed the potent renoprotective potential of moralbosteroid. This was evidenced by the minimized intensity of nephritic cellular destruction. In animal studies, moralbosteroid exhibited dose-dependent activity, which is thought to be mediated through its antioxidant potential.
Gupta, G, Dahiya, R, Dua, K, Chellappan, DK, Tiwari, J, Sharma, GN, Singh, SK, Mishra, A, Sharma, RK & Agrawal, M 2017, 'ANTICONVULSANT EFFECT OF LIRAGLUTIDE, GLP-1 AGONIST BY AVERTING A CHANGE IN GABA AND BRAIN GLUTATHIONE LEVEL ON PICROTOXIN-INDUCED SEIZURES', EXCLI JOURNAL, vol. 16, pp. 752-754.View/Download from: Publisher's site
Hsu, AC-Y, Dua, K, Starkey, MR, Haw, T-J, Nair, PM, Nichol, K, Zammit, N, Grey, ST, Baines, KJ, Foster, PS, Hansbro, PM & Wark, PA 2017, 'MicroRNA-125a and -b inhibit A20 and MAVS to promote inflammation and impair antiviral response in COPD.', JCI insight, vol. 2, no. 7, pp. e90443-e90443.View/Download from: Publisher's site
Influenza A virus (IAV) infections lead to severe inflammation in the airways. Patients with chronic obstructive pulmonary disease (COPD) characteristically have exaggerated airway inflammation and are more susceptible to infections with severe symptoms and increased mortality. The mechanisms that control inflammation during IAV infection and the mechanisms of immune dysregulation in COPD are unclear. We found that IAV infections lead to increased inflammatory and antiviral responses in primary bronchial epithelial cells (pBECs) from healthy nonsmoking and smoking subjects. In pBECs from COPD patients, infections resulted in exaggerated inflammatory but deficient antiviral responses. A20 is an important negative regulator of NF-κB-mediated inflammatory but not antiviral responses, and A20 expression was reduced in COPD. IAV infection increased the expression of miR-125a or -b, which directly reduced the expression of A20 and mitochondrial antiviral signaling (MAVS), and caused exaggerated inflammation and impaired antiviral responses. These events were replicated in vivo in a mouse model of experimental COPD. Thus, miR-125a or -b and A20 may be targeted therapeutically to inhibit excessive inflammatory responses and enhance antiviral immunity in IAV infections and in COPD.
Kikuchi, I, Galante, R, Dua, K, Ghisleni, D, de Jesus Andreoli Pinto, T, Malipeddi, V & Awasthi, R 2017, 'Hydrogel based drug delivery systems: A review with special emphasis on challenges associated with decontamination of hydrogels and biomaterials', Current Drug Delivery, vol. 14, no. 7, pp. 917-925.View/Download from: Publisher's site
Background: Many researches involving the development of new techniques and biomaterials to formulate a suitable drug delivery system and tissue engineering have been conducted. The majority of published literature from these researches emphasizes the production and materials characterization. The safety aspect of hydrogels and biomaterials is a major constraint in their biological applications.
Objective: The present review article aimed to summarize various literatures that encompass the difficulties encountered with decontamination and sterilization methods in the preparations of biomaterials and especially hydrogels for biological applications.
Method: We searched for original and review articles from various indexed journals reporting applications of hydrogels and biomaterials in drug delivery systems and the importance of decontamination process for hydrogel containing preparations based on various patents evidences.
Results: Despite the vast literature available, limited information regarding the decontamination and sterilization processes related to hydrogels and biomaterials is reported. Sterilization processes to hydrogels are not yet fully explored. Researchers working on hydrogel based systems can consider decontamination of such biomaterial as an important tool to allow for commercialization within the chemical, herbal or pharmaceutical industries.
Conclusion: Unfortunately, till date, limited papers are available which reported the challenges associated with decontamination methods to prepare hydrogels and biomaterials for biological applications. In conclusion, each case of biomaterial requires individual consideration to decontamination and/or sterilization. This must be submitted to a specific method, but more than one technique can be involved. Physicochemical and biological alterations must be avoided and evaluated by the appropriate assays method. Furthermore, it is also important to consider that each method must be validated depending up...
Madan, JR, Kamate, VJ, Awasthi, R & Dua, K 2017, 'Formulation, Characterization and In-vitro Evaluation of Fast Dissolving Tablets Containing Gliclazide Hydrotropic Solid Dispersions', Recent Patents on Drug Delivery and Formulation, vol. 11, no. 2, pp. 147-154.View/Download from: Publisher's site
Low aqueous solubility is a major problem faced with new drug molecules. The purpose of this research was to provide a fast dissolving oral dosage form of Gliclazide (GLZ) using the concept of mixed hydrotropy. The recent patents on Adenosine (US20140107059A1), Growth hormone releasing factor peptide (EP0984788A1) and Paclitaxel (WO2002030466A2) helped in selecting the hydrotropes.Solubility of GLZ was determined individually in sodium salicylate, nicotinamide, lactose, sodium acetate, urea, trisodium citrate and sodium benzoate. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope amount, mixed hydrotropic agents were used.Highest solubility was obtained in 25:15 ratio of sodium salicylate and sodium benzoate. This optimized combination was utilized in the preparation of solid dispersions which were evaluated for Xray diffractometry, Differential Scanning Calorimetry (DSC) and Fourier-transform infrared to show no drug-hydrotropes interaction. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus.The batch G3 tablets showed 86% cumulative drug release within 14min with in vitro dispersion time of 33sec. It was concluded that the enhancement in solubility of GLZ is a clear indication of the potential of mixed hydrotropy which is a novel, safe and cost-effective technique to be employed for other poorly water-soluble drugs having low bioavailability.
Madan, JR, Kamate, VJ, Dua, K & Awasthi, R 2017, 'Improving the solubility of nevirapine using A hydrotropy and mixed hydrotropy based solid dispersion approach.', Polimery w medycynie, vol. 47, no. 2, pp. 83-90.View/Download from: Publisher's site
Nevirapine, an antiviral drug, is a potent reverse transcriptase inhibitor (NNRTI). It is used in combination with nucleoside analogues for treatment of HIV type-1 (HIV-1) infection and AIDS. Nevirapine is a BCS class II drug which shows dissolution rate limited absorption.The aim of the present research was to provide a fast dissolving solid dispersion of nevirapine.The solubility of nevirapine was initially determined individually in four hydrotropic agents - namely urea, lactose, citric acid and mannitol - at a concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. The highest solubility was obtained in the 40% citric acid solution. Then different combinations of 2 and 3 hydrotropic agents in different ratios were used to determine solubility, so that the total concentration of hydrotropic agents was always 40%.The highest solubility was obtained in a solution of lactose and citric acid at the optimum ratio of 15:25. This optimized combination was utilized in preparing solid dispersions by a common solvent technique using distilled water as a solvent. The solid dispersions were evaluated for XRD, DSC and FTIR to show no drug-hydrotrope interaction.It was concluded that the concept of mixed hydrotropic solid dispersion is a safe, novel and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs by dissolving the drug in a nonionized form. The enhancement in solubility of nevirapine using hydrotropy is a clear indication of its potential to be used in the future for other poorly water-soluble drugs in which low bioavailability is a major concern.
Madhu, A, Gupta, G, Arali, B, Chellappan, DK & Dua, K 2017, 'Anti-psychotic activity of aqueous root extract of Hemidesmus indicus: A time bound study in rats', Recent Patents on Drug Delivery and Formulation, vol. 11, no. 1, pp. 36-41.View/Download from: Publisher's site
© 2017 Bentham Science Publishers. Aims and Background: Psychosis is a neurological disorder, which is usually defined as the "loss of contact with reality." As medicine 'Hemidesmusindicus' holds a reputed place in all systems of medicine in India. It is given in the form of infusion, fine particles, or syrup. It is also a component of several medicinal preparations. The present research work is pertaining to find out an anti-psychotic activity of an aqueous root extract of Hemidesmusindicus- a time bound study in rats. Methods: In the present study, the dried roots of Hemidesmusindicus were crushed to a coarse powder and extracted with water under reflux for 36 hours to obtain the aqueous extract of roots of Hemidesmusindicus (AERHI). The extract was reconstituted in 2% aqueous tragacanth just before use and administered orally at a dose 0f 100 mg/kg, 300 mg/kg and 500 mg/kg. In a single dose study, the parameters were assessed after oral administration of the single dose of the AERHI, whereas in a multiple dose study, the animals daily received the suitable oral dose of the AERHI for a period of 30 days. The parameters were assessed on the 15th and 30th day. The antipsychotic activity was screened using Apomorphine induced Stereotyped behavior in rats and Haloperidol induced catalepsy models were used. In Apomorphine induced Stereotyped behavior inhibition of the Stereotyped behavior was considered to be anti-psychotic activity and in Haloperidol induced catalepsy, we observed whether the AERHI potentate or attenuate the catalepsy in rats. Results: In this study, the extract of Hemidesmusindicus significantly inhibited the stereotyped behavior induced by apomorphine in rats and also potentiate the catalepsy induced by haloperidol, thereby showing its anti-psychotic activity. Conclusion: All these observations imply that Hemidesmusindicus extract possesses anti-psychotic activity in experimental animals.
Maheshwari, R, Sharma, P, Tekade, M, Atneriya, U, Dua, K, Hansbro, PM & Tekade, RK 2017, 'Microsponge Embedded Tablets for Sustained Delivery of Nifedipine.', Pharmaceutical Nanotechnology, vol. 5, no. 3, pp. 192-202.View/Download from: Publisher's site
Nifedipine is a potential therapeutic agent for the treatment of cardiovascular disturbances, although it suffers from short half-life (t1/2, 2 hr).To address the problem, we first prepared nifedipine loaded sustained release microsponges and then formulated tablets for effective clinical application and patient compliance.Preparations of microsponges were carried out using different compositions of nifedipine and polymer (1:1, 1:2 and 1:3 % molar ratio) using emulsion solvent diffusion technique.The microsponges with molar ratio 1:3 (formulation code: MF-3) found optimized as revealed by analyzing surface morphology, better powder flow properties (angle of repose; 28.80 ± 0.9, Hausner ratio 1.15 ± 0.2, % compressibility 15.28 ± 0.5% and higher % drug content (80 ± 1.9 %). Different batches of tablets were then formulated incorporating MF-3 microsponges and different proportions (10-50 %) of microcrystalline cellulose and starch as additives. Among tablet formulations, batch composed of 48% of MF-3, 30% of MCC, 20 % of starch and 2 % of talc (TF-33), showed 92.73 ± 2.19 % drug release during 24 hr in vitro release study in comparison to other batches including commercial formulation which was found to be released completely in 20 hr. Further, stability analysis revealed good drug retention of loaded nifedipine as well as consistent in vitro release pattern over a period of 90 days at 40°C and 75% RH.The microsponge tablet delivery system was found to be superior concerning the therapeutic advantage as well as manufacturing feasibility of nifedipine.
Mahmood, MQ, Shukla, SD, Dua, K & Shastri, MD 2017, 'The role of epidermal growth factor receptor in the management of gastrointestinal carcinomas: Present status and future perspectives', Current Pharmaceutical Design, vol. 23, no. 16, pp. 2314-2320.View/Download from: Publisher's site
© 2017 Bentham Science Publishers. Background: The global burden of gastrointestinal cancers, including colorectal, stomach, and esophageal cancers is rising steadily. Several therapeutic approaches have been considered for the treatment of GI carcinomas. However, none showed to halt or cure the disease. There is a need to develop effective targeted molecular therapies; mainly to overcome the adverse effects of currently used treatment regimens, as well as, to benefit a large proportion of cancer patients who do not respond well to chemotherapeutics. Methods: Epidermal growth factor receptor (EGFR) is one of the promising targets for cancer therapy. Through a cascade of events, activation of EGFR plays an important role in the homeostasis and pathogenesis of various disorders, including carcinomas of the gastrointestinal (GI) tract, ranging from oesophagitis to complex colon carcinoma. Results: The GI carcinomas are associated with aberrant EGFR expression. In this review, emphasis was made on various EFGR-associated signalling pathways, their mechanisms and role in the formation of gastrointestinal lesions. Conclusion: The current EGFR-targeting therapeutics and an outline of various novel drug delivery systems that could potentially be employed for targeting EGFR during cancer treatment were discussed. This would help medical, pharmaceutical and other life science researchers in providing broad understanding of the work previously conducted in this field.
Malipeddi, VR, Awasthi, R & Dua, K 2017, 'Formulation and evaluation of controlled-release matrix systems of ciprofloxacin.', Polimery w medycynie, vol. 47, no. 2, pp. 101-106.View/Download from: Publisher's site
Ciprofloxacin is a broad-spectrum fluoroquinolone antibacterial drug to which most Gram-negative and many Gram-positive bacteria are highly susceptible. Fluoroquinolones are administered repeatedly, twice a day for 5 days, during the course of therapy. Hence, they require repeated administration. Ciprofloxacin qualifies as a drug candidate for a controlled-release drug delivery system.The present work was aimed to develop ciprofloxacin hydrochloride-containing matrix tablets by the wet granulation method.The tablets were prepared using EthocelTM 100 Premium and Eudragit® RS PO (Evonik Laboratory, Mumbai, India) as a rate-controlling polymer. Granular dioctyl phthalate (DCP) was used as a diluent. An isopropyl alcohol and dichloromethane (1:1) mixture was used as a granulating agent. The effect of the formulation variables on tablet performance was examined based on weight variation, hardness, friability, thickness, and drug release profiles. The results suggested that the tablets had good integrity.The tablets were stable for 18 months. Formulation F7 gave a linear release pattern up to 12 h. The release of ciprofloxacin from formulation F7 followed zero-order kinetics. The release mechanism was found to be diffusion-controlled as the Higuchi equation was obeyed.Ciprofloxacin hydrochloride-containing matrix tablets were prepared successfully. The tablets had good integrity and were found stable for 18 months.
Malipeddi, VR, Awasthi, R, Ghisleni, DDM, Braga, MDS, Kikuchi, IS, Andreoli Pinto, TDJ & Dua, K 2017, 'Preparation and characterization of metoprolol tartrate containing matrix type transdermal drug delivery system', DRUG DELIVERY AND TRANSLATIONAL RESEARCH, vol. 7, no. 1, pp. 66-76.View/Download from: Publisher's site
Sharma, S, Pathak, S, Gupta, G, Sharma, SK, Singh, L, Sharma, RK, Mishra, A & Dua, K 2017, 'Pharmacological evaluation of aqueous extract of syzigium cumini for its antihyperglycemic and antidyslipidemic properties in diabetic rats fed a high cholesterol diet-Role of PPAR gamma and PPAR alpha', BIOMEDICINE & PHARMACOTHERAPY, vol. 89, pp. 447-453.View/Download from: Publisher's site
Singh, Y, Gupta, G, Shrivastava, B, Dahiya, R, Tiwari, J, Ashwathanarayana, M, Sharma, RK, Agrawal, M, Mishra, A & Dua, K 2017, 'Calcitonin gene-related peptide (CGRP): A novel target for Alzheimer's disease.', CNS Neuroscience and Therapeutics, vol. 23, no. 6, pp. 457-461.View/Download from: Publisher's site
Alzheimer's disease (AD) is leading cause of death among older characterized by neurofibrillary tangles, oxidative stress, progressive neuronal deficits, and increased levels of amyloid-β (Aβ) peptides. Cholinergic treatment could be the best suitable physiological therapy for AD. Calcitonin gene-related peptide (CGRP) is a thirty-seven-amino acid regulatory neuropeptide resulting from different merging of the CGRP gene, which also includes adrenomedullin, amylin, calcitonin, intermedin, and calcitonin receptor-stimulating peptide. It is a proof for a CGRP receptor within nucleus accumbens of brain that is different from either the CGRP1 or CGRP2 receptor in which it demonstrates similar high-affinity binding for salmon calcitonin, CGRP, and amylin, a possession which is not shared by any extra CGRP receptors. Binding of CGRP to its receptor increases activated cAMP-dependent pkA and PI3 kinase, resulting in N-terminal fragments that are shown to exert complex inhibitory as well facilitator actions on nAChRs. Fragments such as CGRP1-4, CGRP1-5, and CGRP1-6 rapidly as well as reversibly improve agonist sensitivity of nAChRs without straight stimulating those receptors and produce the Ca2+ -induced intracellular Ca2+ mobilization. Renin-angiotensin-aldosterone system (RAAS)-activated angiotensin-type (AT4) receptor is also beneficial in AD. It has been suggested that exogenous administration of CGRP inhibits infiltration of macrophages and expression of various inflammatory mediators such as NFkB, IL-1b, TNF-α, iNOS, matrix metalloproteinase (MMP)-9, and cell adhesion molecules like intercellular adhesion molecule (ICAM)-1 which attenuates consequence of inflammation in AD. Donepezil, a ChEI, inhibits acetylcholinesterase and produces angiogenesis and neurogenesis, in the dentate gyrus of the hippocampus of WT mice after donepezil administration. However, none of the results discovered in CGRP-knockout mice and WT mice exposed to practical denervation. Therefore, s...
Soni, N, Tekade, M, Kesharwani, P, Bhattacharya, P, Maheshwari, R, Dua, K, Hansbro, PM & Tekade, RK 2017, 'Recent Advances in Oncological Submissions of Dendrimer.', Current pharmaceutical design, vol. 23, no. 21, pp. 3084-3098.View/Download from: Publisher's site
Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients.Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body.Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation.Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.
Tiwari, J, Gupta, G, Dahiya, R, Pabreja, K, Kumar Sharma, R, Mishra, A & Dua, K 2017, 'Recent update on biological activities and pharmacological actions of liraglutide.', EXCLI journal, vol. 16, pp. 742-747.View/Download from: Publisher's site
Velu, V, Das, M, Raj N, AN, Dua, K & Malipeddi, H 2017, 'Evaluation of in vitro and in vivo anti-urolithiatic activity of silver nanoparticles containing aqueous leaf extract of Tragia involucrata.', Drug Delivery and Translational Research, vol. 7, no. 3, pp. 439-449.View/Download from: Publisher's site
The present investigation is focused on exploring the anti-urolithiatic potential of aqueous leaf extract of Tragia involucrata (TIA) and its silver nanoparticles (AgNPs) and to quantify the total phenol, flavonoid, terpenoid and sterol contents present in TIA. Quantification results suggested TIA to be a rich source of phenol, flavonoid and terpenoid and less of sterol content. The AgNPs were synthesized by a simple green method using aqueous extract of T. involucrata. The formation of AgNPs was confirmed through UV spectroscopy, particle size analysis, zeta potential, X-ray diffraction and transmission electron microscopy. The in vitro struvite growth inhibitory activity of the extract was performed using a single gel diffusion method. Samples incorporated with higher concentration of 2% TIA and AgNPs (200 μg mL-1) exhibited potent crystal growth inhibitory activity which was further supported by the dissolution of crystals in gel medium. Calcium oxalate stone formation was induced in rats by the oral administration of ethylene glycol in water. Stone formation was assessed by increase in the levels of calcium and phosphorous in the urine and accumulation of nitrogenous substances like urea, creatinine in renal tissues and blood. Prophylactic treatment with TIA and AgNPs showed significant anti-urolithiatic activity with normalization of the mineral contents of the urine and serum samples. Histopathological analysis of the kidney of TIA- and AgNP-treated animals showed no CaOx deposits and a normal architecture of the kidney cells. We conclude that aqueous extract of T. involucrata and its AgNPs has potential for the treatment of patients with recurrent stones.
Dua, K, Hansbro, NG & Hansbro, PM 2017, 'Steroid resistance and concomitant respiratory infections: A challenging battle in pulmonary clinic.', EXCLI journal, vol. 16, pp. 981-985.View/Download from: Publisher's site
Dua, K, Hansbro, NG, Foster, PS & Hansbro, PM 2017, 'MicroRNAs as therapeutics for future drug delivery systems in treatment of lung diseases', DRUG DELIVERY AND TRANSLATIONAL RESEARCH, vol. 7, no. 1, pp. 168-178.View/Download from: Publisher's site
Hansbro, PM, Kim, RY, Starkey, MR, Donovan, C, Dua, K, Mayall, JR, Liu, G, Hansbro, NG, Simpson, JL, Wood, LG, Hirota, JA, Knight, DA, Foster, PS & Horvat, JC 2017, 'Mechanisms and treatments for severe, steroid-resistant allergic airway disease and asthma.', Immunological reviews, vol. 278, no. 1, pp. 41-62.View/Download from: Publisher's site
Severe, steroid-resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid-resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid-resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid-resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid-resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity-or pollution-associated asthma.
Awasthi, R, Pant, I, T Kulkarni, G, Satiko Kikuchi, I, de Jesus Andreoli Pinto, T, Dua, K & Ramana Malipeddi, V 2016, 'Opportunities and Challenges in Nano-structure Mediated Drug Delivery: Where Do We Stand?', Current Nanomedicine, vol. 6, no. 2, pp. 78-104.View/Download from: Publisher's site
Chellappan, DK, Ganasen, S, Batumalai, S, Candasamy, M, Krishnappa, P, Dua, K, Chellian, J & Gupta, G 2016, 'The protective action of the aqueous extract of Auricularia polytricha in paracetamol induced hepatotoxicity in rats', Recent Patents on Drug Delivery and Formulation, vol. 10, no. 1, pp. 72-76.View/Download from: Publisher's site
© 2016 Bentham Science Publishers. Natural antioxidant products are increasingly being used to treat various pathological liver injuries considering the role of oxidative stress in their pathogenesis. Auricularia polytricha has been used as food or medicine due to its antioxidant activity. The aim of the study was to evaluate the protective effect of the aqueous extract of the fruiting bodies of A. polytricha against paracetamol-induced liver toxicity in rats. Liver toxicity was induced in Sprague–Dawley rats by oral administration of 2g/kg paracetamol on the 15th day after the administration of aqueous extract and silymarin 100 mg/kg. Aqueous extract of A. polytricha was administered orally at 250 and 500 mg/kg doses, daily for a period of 14 days. Aspartate aminotransferase (AST), Alanine transaminase (ALT) and Alkaline phosphatase (ALP), Lactate dehydrogenase (LDH), Total bilirubin (TB), Total protein (TP), Triglycerides (TG) and cholesterol were measured to assess the effect of the extract on paracetamol-induced hepatic damage. The patent on Auricularia Polytricha (EP0413052A1) assisted in selecting the extraction procedure. The study also included histopathological examination of liver sections to assess hepatoprotective activity. Paracetamol significantly (P<0.001) increased the serum AST, ALT, ALP, LDH, TB, TG and cholesterol and decreased TP levels. Extract treatment significantly (P<0.001 to P<0.05) attenuated the paracetamol induced increase in AST, ALT, ALP, LDH, TB, TG and cholesterol and increased the diminished TP in a dose dependent manner. The standard drug, silymarin produced significant (P<0.001) decrease in AST, ALT, ALP, LDH, TB, TG and cholesterol and increase in TP. Histopathological examination of animals treated with paracetamol showed large areas of centrilobular necrosis with congestion and dilatation in both central and portal veins. These results indicate that the aqueous extract of A. polytricha has significant protective effect again...
Dhiman, N, Awasthi, R, Jindal, S, Khatri, S & Dua, K 2016, 'Development of Bilayer Tablets with Modified Release of Selected Incompatible Drugs', Polimery w medycynie, vol. 46, no. 1, pp. 5-15.View/Download from: Publisher's site
BACKGROUND: The oral route is considered to be the most convenient and commonly-employed route for drug delivery. When two incompatible drugs need to be administered at the same time and in a single formulation, bilayer tablets are the most appropriate dosage form to administer such incompatible drugs in a single dose.OBJECTIVES: The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin.MATERIAL AND METHODS: The bilayer tablets were prepared containing telmisartan in a conventional release layer using croscarmellose sodium as a super disintegrant and simvastatin in a slow-release layer using HPMC K15M, Carbopol 934P and PVP K 30 as matrix forming polymers. The tablets were evaluated for various physical properties, drug-excipient interactions using FTIR spectroscopy and in vitro drug release using 0.1M HCl (pH 1.2) for the first hour and phosphate buffer (pH 6.8) for the remaining period of time. The release kinetics of simvastatin from the slow release layer were evaluated using the zero order, first order, Higuchi equation and Peppas equation.RESULTS: All the physical parameters (such as hardness, thickness, disintegration, friability and layer separation tests) were found to be satisfactory. The FTIR studies indicated the absence of interactions between the components within the individual layers, suggesting drug-excipient compatibility in all the formulations. No drug release from the slow-release layer was observed during the first hour of the dissolution study in 0.1M HCl. The release-controlling polymers had a significant effect on the release of simvastatin from the slow-release layer. Thus, the formulated bilayer tablets avoided incompatibility issues and proved the conventional release of telmisartan (85% in 45 min) and slow release of simvastatin (80% in 8 h).CONCLUSIONS: Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient comp...
Dua, K, Malipeddi, VR, Madan, J, Gupta, G, Chakravarthi, S, Awasthi, R, Kikuchi, IS & De Pinto, TJA 2016, 'Norfloxacin and metronidazole topical formulations for effective treatment of bacterial infections and burn wounds', Interventional Medicine and Applied Science, vol. 8, no. 2, pp. 68-76.View/Download from: Publisher's site
© 2016 The Author(s). Introduction: Our various previous findings have shown the suitability of norfloxacin in the treatment of bacterial infections and burn wounds in alone as well as in combination with Curcuma longa in various topical (ointments, gels, and creams) and transdermal drug delivery systems. Aims and methods: Keeping these facts in consideration, we have made an another attempt to prepare semisolid formulations containing 1% w/w of norfloxacin and metronidazole with different bases like Carbopol, polyethylene glycol, and hydroxypropylmethyl cellulose for effective treatment of bacterial infections and burn wounds. The prepared formulations were evaluated for physicochemical parameters, in vitro drug release, antimicrobial activity, and burn wound healing properties. Results: The prepared formulations were compared with Silver Sulfadiazine cream 1%, USP. Antimicrobial activity of norfloxacin semisolid formulations was found to be equally effective against both aerobic and anaerobic bacteria in comparison to a marketed formulation of Silver Sulfadiazine 1% cream, USP. Based on the burn wound healing property, the prepared norfloxacin semisolid formulation was found to be in good agreement with marketed Silver Sulfadiazine 1% cream, USP. Conclusions: These findings suggest formulations containing norfloxacin and metronidazole may also prove as an effective alternative for existing remedies in the treatment of bacterial infections and burn wounds.
Ghisleni, DDM, Bragaa, MDS, Kikuchia, IS, Brasoveanu, M, Nemtanu, MR, Dua, K & Andreoli Pinto, TDJ 2016, 'The Microbial Quality Aspects and Decontamination Approaches for the Herbal Medicinal Plants and Products: An in-Depth Review', CURRENT PHARMACEUTICAL DESIGN, vol. 22, no. 27, pp. 4264-4287.View/Download from: Publisher's site
Madan, JR, Ghuge, NP & Dua, K 2016, 'Formulation and evaluation of proniosomes containing lornoxicam', DRUG DELIVERY AND TRANSLATIONAL RESEARCH, vol. 6, no. 5, pp. 511-518.View/Download from: Publisher's site
Malipeddi, VR, Awasthi, R & Dua, K 2016, 'Formulation and evaluation of controlled release ethylcellulose and polyethylene glycol microspheres containing metoprolol tartrate', Interventional Medicine and Applied Science, vol. 8, no. 2, pp. 60-67.View/Download from: Publisher's site
© 2016 The Author(s). Metoprolol tartrate is rapidly absorbed from both gastric and intestinal regions, after oral administration. To retard the release rate of the metoprolol tartrate, microspheres were prepared with varying concentrations of a mixture containing ethylcellulose and polyethylene glycol-6000. The prepared microspheres were evaluated for various physicochemical characteristics and in vitro drug release. The percent yield of microspheres was in the range of 75.2-87.3%. The particle size of microspheres was found to be in the range of 73.2-85.5 μm. Fourier transform-infrared spectral analysis and differential scanning calorimetry concluded the absence of any interaction between the drug and the carriers. The release time profile of metoprolol tartrate from microspheres in 0.1 N hydrochloric acid solution was to the extent of 33.4-60.2%. The complete release of metoprolol tartrate occurred from MPT-3 and MPT-4 in phosphate buffer solution (pH 7.4) within 8 and 7 h, respectively, whereas the incomplete release (72.3%) occurred from MPT-1. Nearly, the complete release (98.5%) of metoprolol occurred from MPT-2 in 10 h. Formulation MPT-2 would be a preferred formulation. The release of metoprolol involves diffusion rate limited (R2 = 0.9865) as a mechanism from drug release. The prepared microspheres of metoprolol tartrate eliminate the need for multiple dosing and provide patient compliance.
Malipeddi, VR, Dua, K & Awasthi, R 2016, 'Development and characterization of solid dispersion-microsphere controlled release system for poorly water-soluble drug', DRUG DELIVERY AND TRANSLATIONAL RESEARCH, vol. 6, no. 5, pp. 540-550.View/Download from: Publisher's site
Maurya, H, Dhiman, S, Dua, K & Gupta, G 2016, 'Pharmacological effect of berberine chloride in propyl thiouracil induced thyroidal dysfunction - A time bound study in female rats', Recent Patents on Drug Delivery and Formulation, vol. 10, no. 2, pp. 165-173.View/Download from: Publisher's site
© 2016 Bentham Science Publishers. Background: The present study is aimed at bringing out the information on the effect of berberine chloride in hyper and hypo thyroidal model with two dose levels. Objective: The research article also reviewed details of various existing patents associated with comprehensive compilation regarding the therapeutic application of berberine and related forms. Method: Sixty female wistar rats weighing between 150-250 gm were divided in to 10 groups. The animals were grouped in to solvent control; hypothyroid; hyperthyroid; prophylactic with two different doses of berberine chloride (50 and 100 mg/kg); treatment groups similar to that of the prophylactic and therapeutic group. To substantiate the dose dependent effect of berberine chloride in 6-n-propyL-2-thiouracil (PTU) induced hypothyroidism, lipid profile, thyroid profile, enzymes profiles and blood profiles, in addition to histopathological studies were also carried out. There was no any significant difference in the lipid profile among solvent control, treatment and prophylactic groups. However, there was a significant difference (***p<0.001) in serum triglycerides, LDL and VLDL of hypothyroid group when compound to that of the rest. Results: As far as thyroid profile is concerned, T3 level of berberine chloride (50 mg/kg) treated groups (prophylactic+ treatment) showed a significant rise compared to hypothyroid group. TSH level in prophylactic groups was far higher than the rest of the groups (3.002±0.0192, 1.051±0.0008 against the solvent control, 0.308±0.008). SGOT, SGPT levels were significantly higher with the therapeutic group than that of the normal and hypo-thyroidal group. Blood profile of berberine chloride (100 mg/kg) treated therapeutic group was comparable to that of the solvent control than all other groups. The probable mechanism underlying may be that inactivation of type I 5ʹ-iodothyronine deiodinase (5ʹDI) enzyme by NF-κB pathway. Conclusion: From the findings o...
Rediguieri, CF, Sassonia, RC, Dua, K, Kikuchi, IS & Andreoli Pinto, TDJ 2016, 'Impact of sterilization methods on electrospun scaffolds for tissue engineering', EUROPEAN POLYMER JOURNAL, vol. 82, pp. 181-195.View/Download from: Publisher's site
Wark, P, Hsu, A, Starkey, M & Hansbro, P 2016, 'Micro-RNA-125a/b target A20 and MAVS to promote inflammatory and impair antiviral responses in chronic obstructive pulmonary disease', EUROPEAN RESPIRATORY JOURNAL, vol. 48.View/Download from: Publisher's site
Dua, K, Sheshala, R, Al-Waeli, HA, Gupta, G & Chellappan, DK 2015, 'Antimicrobial efficacy of extemporaneously prepared herbal mouthwashes', Recent Patents on Drug Delivery and Formulation, vol. 9, no. 3, pp. 201-205.View/Download from: Publisher's site
© 2015 Bentham Science Publishers. Natural products like plants and its components have been in use for treatment and cure of diseases all around the globe from ancient times much before the discovery of the current modern drugs. These substances from the nature are well known to contain components which have therapeutic properties and can also behave as precursors for the synthesis of potential drugs. The beneficial results from herbal drugs are well reported where their popularity in usage has increased across the globe. Subsequently developing countries are now recognizing the many positive advantages from their use which has engaged the expansion of R & D from herbal research. The flow on effect from this expansion has increased the awareness to develop new herbal products and the processes, throughout the entire world. Mouth washes and mouth rinses which have plant oils, plant components or extracts have generated particular attention. High prevalence of gingival inflammation and periodontal diseases, suggests majority of the patients practice inadequate plaque control. Of the currently available mouthwashes in the market, Chlorhexidine gluconate (CHX) has been investigated on a larger scale with much detail. CHX is associated with side effects like staining of teeth when used daily as well as the bitter taste of the mouthwash which leads to patient incompliance. The present research encompasses the antibacterial activity of extemporaneously prepared herbal mouthwash using natural herbs and therefore allows for the potential commercialization with in the herbal and pharmaceutical industries. Also, the present research article reviewed details of various existing patents of herbal mouthwashes which shows the trend of existing market and significance of emerging mouthwashes in both pharmaceutical and herbal industries. The antimicrobial activity of prepared mouthwashes was found to be effective against various strains of bacteria. It also suggests that the pre...
Dua, K, Sheshala, R, Al-Waeli, HA, Gupta, G & Chellappan, DK 2015, 'Antimicrobial Efficacy of Extemporaneously Prepared Herbal Mouthwashes.', Recent Patents on Drug Delivery and Formulation, vol. 9, no. 3, pp. 257-261.View/Download from: Publisher's site
Natural products like plants and its components have been in use for treatment and cure of diseases all around the globe from ancient times much before the discovery of the current modern drugs. These substances from the nature are well known to contain components which have therapeutic properties and can also behave as precursors for the synthesis of potential drugs. The beneficial results from herbal drugs are well reported where their popularity in usage has increased across the globe. Subsequently developing countries are now recognizing the many positive advantages from their use which has engaged the expansion of R & D from herbal research. The flow on effect from this expansion has increased the awareness to develop new herbal products and the processes, throughout the entire world. Mouth washes and mouth rinses which have plant oils, plant components or extracts have generated particular attention. High prevalence of gingival inflammation and periodontal diseases, suggests majority of the patients practice inadequate plaque control. Of the currently available mouthwashes in the market, Chlorhexidine gluconate (CHX) has been investigated on a larger scale with much detail. CHX is associated with side effects like staining of teeth when used daily as well as the bitter taste of the mouthwash which leads to patient incompliance. The present research encompasses the antibacterial activity of extemporaneously prepared herbal mouthwash using natural herbs and therefore allows for the potential commercialization with in the herbal and pharmaceutical industries. Also, the present research article reviewed details of various existing patents of herbal mouthwashes which shows the trend of existing market and significance of emerging mouthwashes in both pharmaceutical and herbal industries. The antimicrobial activity of prepared mouthwashes was found to be effective against various strains of bacteria. It also suggests that the prepared herbal mouthwashes may provid...
Gorajana, A, Kit, WW & Dua, K 2015, 'Characterization and solubility study of norfloxacin-polyethylene glycol, polyvinylpyrrolidone and carbopol 974p solid dispersions', Recent Patents on Drug Delivery and Formulation, vol. 9, no. 2, pp. 167-182.View/Download from: Publisher's site
© 2015, Bentham Science Publishers. Objective: Norfloxacin has a low aqueous solubility which leads to poor dissolution. Keeping this fact in mind the purpose of the present study is to formulate and evaluate norfloxacin solid dispersion. Methods: Solid dispersions were prepared using hydrophilic carriers like polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974pNF (CP) in various ratios using solvent evaporation technique. These formulations were evaluated using solubility studies, dissolution studies; Fourier transmitted infrared spectroscopy (FTIR), X-ray diffraction (XRD), and differential scanning calorimetery (DSC). The influence of polymer type and drug to polymer ratio on the solubility and dissolution rate of norfloxacin was also evaluated. Results: FTIR analysis showed no interaction of all three polymers with norfloxacin. The results from XRD and DSC analyses of the solid dispersion preparations showed that norfloxacin existsin its amorphous form. Among the Norfloxacin: PEG solid dispersions, Norfloxacin: PEG 1:14 ratio showed the highest dissolution rate at pH 6.8. For norfloxacin: PVP solid dispersions, norfloxacin: PVP 1:10 ratio showed the highest dissolution rate at pH 6.8. For Norfloxacin: CP solid dispersions, norfloxacin: P 1:2 ratio showed the highest dissolution rate at pH 6.8. Conclusion: The solid dispersion of norfloxacin with polyethylene glycol (PEG) 4000, polyvinylpyrrolidone (PVP) k30 and carbopol 974p NF (CP), lends an ample credence for better therapeutic efficacy.
Gorajana, A, Rajendran, A, Yew, LM & Dua, K 2015, 'Preparation and characterization of cefuroxime axetil solid dispersions using hydrophilic carriers.', International journal of pharmaceutical investigation, vol. 5, no. 3, pp. 171-178.View/Download from: Publisher's site
AIM: The objective of the current study is to increase the dissolution rate of cefuroxime axetil (CA) by formation of binary CA solid dispersion using water soluble carriers such as polyvinylpyrrolidone (PVP K30) and polyethylene glycol (PEG 4000). METHODS: Solid dispersions (SDs) between CA and PVP K30/PEG 4000 were formed by dissolving both compounds in a common solvent, methanol, which were rotary evaporated at 40°C for 12 h. Physical mixtures between CA and PVP K30/PEG 4000 were also formulated as to compare the efficiency of SDs. The physicochemical properties of CA and all its formulations were then characterized using differential scanning calorimetric analysis (DSC), powder X-ray diffraction studies (PXRD), and Fourier transform infrared spectroscopy (FTIR). RESULTS: All SD formulations were found to have a higher dissolution rate comparatively to pure CA, while only physical mixtures of PVP K30 were found having a significantly higher dissolution rate. The enhancement of dissolution rate SD by PVP K30 may be caused by increase wettability, solubility, reduction in particle size or the formation of CA β crystalline. Increment of dissolution rate of CA SDs by PEG 4000 similarly may be caused by increase wettability, solubility, and reduction in particle size. This phenomenon may also be caused by amorphization as suggested by DSC and PXRD. CONCLUSIONS: The SD of CA with PVP K30 and PEG 4000, lends an ample credence for better therapeutic efficacy.
Gupta, G, Jia Jia, T, Yee Woon, L, Kumar Chellappan, D, Candasamy, M & Dua, K 2015, 'Pharmacological Evaluation of Antidepressant-Like Effect of Genistein and Its Combination with Amitriptyline: An Acute and Chronic Study', Advances in Pharmacological Sciences, vol. 2015, pp. 1-6.View/Download from: Publisher's site
© 2015 Gaurav Gupta et al. The present study was designed to evaluate the acute and chronic antidepressant effect of genistein in combination with amitriptyline in mice. Animals were divided into six groups (n=6) for treatment with water, genistein, or amitriptyline, either alone or in combination for ten days. Animals were subjected to locomotor activity testing; tail suspension test (TST); and forced swim test (FST) and immobility time was recorded on day one and day ten. Acute treatment of all treatment groups did not significantly reduce the immobility time (p > 0.05). Chronic treatment of combination of genistein (10 mg/kg) and amitriptyline (5 mg/kg and 10 mg/kg) significantly reduced the immobility time as compared to control group (p < 0.001) and was comparable to amitriptyline alone (10 mg/kg). However, no changes in anti-immobility activity in combination of subeffective doses of genistein (5 mg/kg) and amitriptyline (5 mg/kg) were observed. Genistein at its standard dose (10 mg/kg) rendered synergistic effects in combination with subeffective dose of amitriptyline (5 mg/kg) and additive effects in combination with therapeutic dose of amitriptyline (10 mg/kg).
Madan, JR, Adokar, BR & Dua, K 2015, 'Development and evaluation of in situ gel of pregabalin.', International journal of pharmaceutical investigation, vol. 5, no. 4, pp. 226-233.View/Download from: Publisher's site
Pregabalin (PRG), an analog of gamma-aminobutyric acid, reduces the release of many neurotransmitters, including glutamate, and noradrenaline. It is used for the treatment of epilepsy; simple and complex partial convulsion. The present research work aims to ensure a high drug absorption by retarding the advancement of PRG formulation through the gastrointestinal tract. The work aims to design a controlled release PRG formulation which is administered as liquid and further gels in the stomach and floats in gastric juice.In situ gelling formulations were prepared using sodium alginate, calcium chloride, sodium citrate, hydroxypropyl methylcellulose (HPMC) K100M, and sodium bicarbonate. The prepared formulations were evaluated for solution viscosity, drug content, in vitro gelling studies, gel strength, and in vitro drug release. The final formulation was optimized using a 3(2) full factorial design.The formulation containing 2.5% w/v sodium alginate and 0.2% w/v calcium chloride were considered optimum since it showed minimum floating lag time (18 s), optimum viscosity (287.3 cps), and gel strength (4087.17 dyne/cm(2)). The optimized formulation follows Korsmeyer-Peppas kinetic model with n value 0.3767 representing Fickian diffusion mechanism of drug release.Floating in situ gelling system of PRG can be formulated using sodium alginate as a gelling polymer and calcium chloride as a complexing agent to control the drug release for about 12 h for the treatment of epilepsy.
Madan, JR, Argade, NS & Dua, K 2015, 'Formulation and evaluation of transdermal patches of donepezil', Recent Patents on Drug Delivery and Formulation, vol. 9, no. 1, pp. 95-103.View/Download from: Publisher's site
© 2015 Bentham Science Publishers. Aims and Background: Donepezil (DNZ) is a centrally acting reversible acetyl cholinesterase inhibitor. The main therapeutic use of donepezil is in the treatment of Alzheimer's disease. The present research work pertains to the preparation of transdermal patches of donepezil with the objective to improve its patient compliance, therapeutic efficacy and to reduce the frequency of dosing and side effects as well as to avoid its extensive first pass metabolism. The recent patents on Rivastigmine (WO2013150542A2), Xanomeline (US5980933A) and Propentofylline (CA2255580A1) helped in selecting the drug and polymers. Materials and Methods: The transdermal patches were prepared using various polymers in combination with the plasticizer and penetration enhancers. The physicochemical parameters like folding endurance, thickness, drug content, content uniformity, moisture absorption, weight variation, and drug permeation studies of the optimized patches were studied. Results: The system containing Eudragit S-100, Eudragit E-100 and HPMC as matrix forming agent and glycerine as plasticizer was the best formulation. The in vitro release data was treated with kinetic equations and it followed zero order release. The diffusion study was carried out using rat skin showed 89% drug was released within 72 hours. Tween-80 (0.83% w/w) was found to be the best among all penetration enhancers. All the transdermal patches had the desired physical properties like tensile strength, folding endurance, flatness and water vapor transmission rate etc. Conclusion: The study concluded that that transdermal patch can extend the release of donepezil for many hours and also ensure enhanced bioavailability, further it also helps in avoiding the first pass effect.
Madan, JR, Pawar, KT & Dua, K 2015, 'Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy.', International journal of pharmaceutical investigation, vol. 5, no. 2, pp. 114-120.View/Download from: Publisher's site
Low aqueous solubility is a major problem faced during formulation development of new drug molecules. Lurasidone HCl (LRD) is an antipsychotic agent specially used in the treatments of schizophrenia and is a good example of the problems associated with low aqueous solubility. Lurasidone is practically insoluble in water, has poor bioavailability and slow onset of action and therefore cannot be given in emergency clinical situations like schizophrenia. Hence, purpose of this research was to provide a fast dissolving oral dosage form of Lurasidone. This dosage form can provide quick onset of action by using the concept of mixed hydrotropy. Initially, solubility of LRD was determined individually in nicotinamide, sodium citrate, urea and sodium benzoate at concentration of 10, 20, 30 and 40% w/v solutions using purified water as a solvent. Highest solubility was obtained in 40% sodium benzoate solution. In order to decrease the individual hydrotrope concentration mixed hydrotropic agents were used. Highest solubility was obtained in 15:20:5 ratio of Nicotinamide + sodium benzoate + sodium citrate. This optimized combination was utilized in the preparation of solid dispersions by using distilled water as a solvent. Solid dispersions were evaluated for X-ray diffraction, differential scanning calorimetry and Fourier-transform infrared to show no drug-hydrotropes interaction has occurred. This solid dispersion was compressed to form fast dissolving tablets. Dissolution studies of prepared tablets were done using USP Type II apparatus. The batch L3 tablets show 88% cumulative drug release within 14 min and in vitro dispersion time was 32 min. It was concluded that the concept of mixed hydrotropic solid dispersion is novel, safe and cost-effective technique for enhancing the bioavailability of poorly water-soluble drugs. The miraculous enhancement in solubility and bioavailability of Lurasidone is clear indication of the potential of mixed hydrotropy to be used in future...
Sheshala, R, Kok, YY, Ng, JM, Thakur, RRS & Dua, K 2015, 'In situ gelling ophthalmic drug delivery system: An overview and its applications', Recent Patents on Drug Delivery and Formulation, vol. 9, no. 3, pp. 242-253.View/Download from: Publisher's site
© 2015 Bentham Science Publishers. Ophthalmic drug delivery system is very interesting and challenging due to the normal physiologically factor of eyes which reduces the bioavailability of ocular products. The development of new ophthalmic dosage forms for existing drugs to improve efficacy and bioavailability, patient compliance and convenience has become one of the main trend in the pharmaceuticals industry. The present review encompasses various conventional and novel ocular drug delivery systems, methods of preparation, characterization and recent research in this area. Furthermore, the information on various commercially available in situ gel preparations and the existing patents of in situ drug delivery systems i.e. in situ gel formation of pectin, in situ gel for therapeutic use, medical uses of in situ formed gels and in situ gelling systems as sustained delivery for front of eye are also covered in this review.
Sheshala, R, Kok, YY, Ng, JM, Thakur, RRS & Dua, K 2015, 'In Situ Gelling Ophthalmic Drug Delivery System: An Overview and Its Applications.', Recent Patents on Drug Delivery and Formulation, vol. 9, no. 3, pp. 237-248.View/Download from: Publisher's site
Ophthalmic drug delivery system is very interesting and challenging due to the normal physiologically factor of eyes which reduces the bioavailability of ocular products. The development of new ophthalmic dosage forms for existing drugs to improve efficacy and bioavailability, patient compliance and convenience has become one of the main trend in the pharmaceuticals industry. The present review encompasses various conventional and novel ocular drug delivery systems, methods of preparation, characterization and recent research in this area. Furthermore, the information on various commercially available in situ gel preparations and the existing patents of in situ drug delivery systems i.e. in situ gel formation of pectin, in situ gel for therapeutic use, medical uses of in situ formed gels and in situ gelling systems as sustained delivery for front of eye are also covered in this review.
Dua, K 2014, 'Statistical Design for Optimization and Determination of Tizanidine Hcl using Folin-Ciocalteu (Fc) as Chromogenic Reagent', Pharmaceutica Analytica Acta, vol. 5, no. 8, pp. 1-5.View/Download from: Publisher's site
A simple, sensitive spectrophotometric method has been developed for quantitative determination of Tizanidine
Hydrochloride in bulk and pharmaceutical formulations with application of factorial design. In this method, Tizanidine
Hydrochloride is made to react with Folin-Ciocalteu (FC) reagent under alkaline conditions forming a blue chromogen
having absorption maximum at 663 nm. Beer's law was obeyed in the concentration range of 4-36 μg/ml. Results
of the analysis were validated as per ICH guidelines and by recovery studies. A 3-factor, 3-level statistical design
(Box-Behnken) was used to derive a second-order polynomial equation to construct contour plots for prediction of
response. Independent variables studied were the FC-reagent (X1), sodium carbonate (X2) and drug concentration
(X3) and the levels of each factor were low, medium, and high. The dependent variable studied was absorbance
(Y1). The aims of this study to determination and optimize the Tizanidine HCl using FC as Chromogenic reagent; the
design demonstrated the role of the derived equation (polynomial) and two dimensional plots in predicting the values
of dependent variable for optimization.
Gupta, G, Dua, K, Kazmi, I & Anwar, F 2014, 'Anticonvulsant activity of Morusin isolated from Morus alba: Modulation of GABA receptor', Biomedicine and Aging Pathology, vol. 4, no. 1, pp. 29-32.View/Download from: Publisher's site
Aim of the study Epilepsy is a complex neurological disorder affecting 50 million of world's total population. Number of medicinal plants has been used to treat the convulsion. In ancient time Morus alba was used to treat epilepsy and mental illness. In Chinese medicine also M. alba is used as neuroprotective herbs. The present study was designed to explore the effect of Morusin, a flavonoid glycoside isolated from M. alba as anticonvulsant activity along with biochemical mechanism. Materials and methods Morusin was isolated from M. alba and acute toxicity study was determined. Anticonvulsant activity of Morusin (5 and 10 mg/kg, i.p.) was studied by using isoniazid (INH) and maximal electroshock (MES)-induced convulsion models; diazepam (5 mg/kg) and phenytoin (20 mg/kg) were used as standards, respectively. Biochemical mechanism was investigated by estimating the GABA level in brain. Results The median lethal dose (LD50) of Morusin was found up to 20 mg/kg. Treatment with Morusin (5 and 10 mg/kg) delayed onset of convulsion and tonic hind limb extension along with duration of tonic-clonic convulsions as well as it significantly reduced mortality in INH and MES-induced convulsion. Rats treated with Morusin (5 and 10 mg/kg) significantly increased level of brain GABA at both doses. Conclusion The findings of current study provide pharmacological credibility to anticonvulsant activity of Morusin. The protection against the convulsions and restoration of GABA level give a suggestion to its probable mechanism of action. © 2013 Elsevier Masson SAS.
Gupta, G, Krishna, G, Chellappan, DK, Gubbiyappa, KS, Candasamy, M & Dua, K 2014, 'Protective effect of pioglitazone, a PPAR gamma agonist against acetaminophen-induced hepatotoxicity in rats', MOLECULAR AND CELLULAR BIOCHEMISTRY, vol. 393, no. 1-2, pp. 223-228.View/Download from: Publisher's site
Gupta, G, Verma, R, David, SR, Chellappan, DK, Anwar, F & Dua, K 2014, 'Hepatoprotective activity of moralbosteroid, a steroidal glycoside isolated from Morus alba', Oriental Pharmacy and Experimental Medicine, vol. 14, no. 3, pp. 285-289.View/Download from: Publisher's site
This study evaluates the hepatoprotective activity of moralbosteroid, isolated from Morus alba, against the hepatotoxicity induced by CCl4 in wistar albino rats. The level of hepatoprotection was estimated by measuring the following biochemical markers: aspartate amino-transferase (AST), alkaline phosphatase (ALP), serum alanine amino-transferase (ALT), total bilirubin (TB), and total protein (TP), including the enzymes involved in antioxidant activities like glutathione transferase (GST), glutathione peroxidase (GPx), catalase (CAT), lipid peroxidation (LPO) and superoxide dismutase (SOD). The oral administration of CCl4 significantly caused elevation in LPO level (13.22 ± 1.59 μM/mg protein) as compared to control. The activities of antioxidant enzymes including CAT, SOD, GPx and GST were decreased significantly (0.38 ± 0.6 nmol/min/ml, 0.89 ± 0.83 U/ml, 3.90 ± 0.91 μmol and 0.05 ± 0.16 U/min/mg protein) in testicular tissue as compared to control animals. Moralbosteroid significantly prevents the marked escalation of serum markers and inhibited the free radical processes by the scavenging of hydroxyl radicals. It also modulates the levels of LPO and prominently increases the endogenous antioxidant enzyme levels in hepatocellular toxicity induced by CCl4. The results obtained in the present study suggest the preventive influence of moralbosteroid on liver toxicity in rats induced by CCl4 comparable with those of Silymarin. © 2014 Institute of Korean Medicine, Kyung Hee University.
Kamal Dua, VK 2014, 'Taguchi and Quadratic via Chromogenic Design Methodology: A Better to Best Estimation Process (Tizanidine Hcl) Bulk/Pharmaceutical', Pharmaceutica Analytica Acta, vol. 5, no. 9, pp. 1-5.View/Download from: Publisher's site
A finest quantitative responsive with reproducible best method was developed using designed array (Taguchi) and Quadratic design methodology (RSM) chromomeric spectrophotometric estimation of bulk as well as pharmaceutical (Tizanidine HCl). Initially (Taguchi), orthogonal array design was applied to find significant variables as well as optimum (better) levels. By response surface (central composite; quadratic) methodology were used to ascertain optimum to optimized "Better to Best" and studied values of variables (independent significant; X1=PDAB=chromogenic reagent; FeCl3=X2=ferric ion at optimum levels with drug constant=X3) responses (dependent Y1=absorbance) models at positive and negative (+1/-1 optimum spaces) levels. More-more, designed independent factorial levels "better to best" surface models (3D) and its polynomial (2nd order) equation was predicted the finest level which further can be considered as best chromomeric estimation method. The models analysis of experimental variables and their level showed and followed good Beer's (5-50 μg/ml) correlation at optimized significant independent best (finest) level variables and in-addition validated using pharmaceutical guidelines (ICH; international conference on harmonization) for human use.
Madan, J, Sudarshan, B, Kadam, V & Kamal, D 2014, 'Formulation and development of self-microemulsifying drug delivery system of pioglitazone hydrochloride', Asian Journal of Pharmaceutics, vol. 8, no. 1, pp. 27-34.View/Download from: Publisher's site
Self-microemulsifying drug delivery system (SMEDDS) is a promising system for the Biopharmaceutics Classification System (BCS) class II drugs. The current research aimed to improve the dissolution of poorly water-soluble antidiabetic drug pioglitazone HCl by formulating it in SMEDDS. Liquid SMEDDS of pioglitazone HCl were formulated with Capmul MCM C8 and oleic acid as oil phase, Cremophor RH 40 and Tween 80 as surfactant phase, and Transcutol P as cosurfactant phase after screening various vehicles. The prepared formulations were evaluated for self-emulsifying ability and phase diagram was constructed to optimize the system. These systems were further characterized for globule size, effect of pH and robustness, zeta potential, drug content, viscosity, self-emulsification time, polydispersity index, % transmittance, thermodynamic stability, surface morphology, and drug release. The system was robust to different pH media and dilution volumes. The optimized system possessed a mean globule size of 122.2 nm, zeta potential around -22.9 mV, drug content 99.66 +- 0.47%, viscosity 0.8874 +- 0.026 cP, emulsification time 38 s, polydispersity index value of 0.5, and transmittance value of 99.3 +- 0.6%. Drug release in hydrochloric acid buffer pH 2 was found to be 99.35 +- 0.38%. More than three-fold increase in dissolution characteristics of pioglitazone HCl in SMEDDS was observed as compared to pure and marketed formulation. Liquid SMEDDS filled in hard gelatin capsule (HGC) shell was found to be compatible. Stability studies show there was no sign of phase separation or precipitation and no change in drug content was observed.
Madan, JR, Khude, PA & Dua, K 2014, 'Development and evaluation of solid lipid nanoparticles of mometasone furoate for topical delivery.', International journal of pharmaceutical investigation, vol. 4, no. 2, pp. 60-64.View/Download from: Publisher's site
INTRODUCTION: Solid lipid nanoparticles (SLNs) are the new generation of submicron sized lipid emulsions where liquid lipid (oil) has been substituted by solid lipid. Lipids used in the formulation are safe, stable and biodegradable in nature. SLNs offer various advantages for topical drug delivery like ability of deposition into skin with the reduced systemic exposure and reduced local side-effects along with providing sustained release of drug. Mometasone furoate (MF) is a topical glucocorticoid having anti-inflammatory, anti-pruritic, anti-hyper proliferative activity. Owing to these properties it is recommended in chronic inflammation and psoriasis. In market, MF cream and lotion (0.1%) are available, which show slight skin irritation, burning and common side-effects due to steroids. EXPERIMENTAL: To overcome the shortcomings of conventional formulations, there is a need to develop a novel formulation that can reduce these side-effects and show maximum desired effects. Thus, SLN of MF can be prepared, which would help in increasing skin deposition as well as provide sustained release. In this study, SLNs were prepared by solvent - injection method. RESULTS: The F8 batch had shown maximum entrapment up to55.59% and sustained drug release for more than 8 h. The skin permeability of SLN loaded gel was found to be 15.21times more than that of marketed cream. SLN loaded gel showed 83.52% of skin deposition which was 2.67 times more than marketed cream and 20 times more than plain drug loaded gel. The scanning electron microscopy and zeta potential study showed formation of good SLN dispersion. The stability study showed successful formation of stable SLNs. Thus, SLNs proved the potential for topical delivery of corticosteroid drug over the conventional formulations. EXPERIMENTAL: To overcome the shortcomings of conventional formulations, there is a need to develop a novel formulation that can reduce these side-effects and show maximum desired effects. Thus, SLN of...
Sharma, A, Prasad, A, Dua, K & Singh, G 2014, 'Effect of combination of acrylic polymers on the release of nevirapine formulated as extended release matrix pellets using extrusion and spheronization technique.', Current Drug Delivery, vol. 11, no. 5, pp. 643-651.View/Download from: Publisher's site
The aim of the present research work was to formulate and evaluate the extended release matrix pellets of nevirapine using extrusion and spheronization technique which will be an alternative technique for making extended release dosage forms and to compare the drug release profiles of the formulations with the reference product. In vitro dissolutions were carried out in 0.04M Phosphate buffer pH 6.8 with 2% w/v SLS (sodium lauryl sulphate) for 24 hours with USP type I apparatus at 75rpm. The drug release from the optimised formulation was comparable to that of the reference product and follows first order kinetics followed by non-fickian transport mechanism of drug release which confirms the drug release pattern involves complex mixture of diffusion and erosion. The similarity factor, f2 value of optimised formulation was found to be 70, which shows that the developed formulation was comparable to that of the reference product.
Dua, K, Chakravarthi, S, Kumar, D, Sheshala, R & Gupta, G 2013, 'Formulation, characterization, in vitro, in vivo, and histopathological evaluation of transdermal drug delivery containing norfloxacin and Curcuma longa.', International journal of pharmaceutical investigation, vol. 3, no. 4, pp. 183-187.View/Download from: Publisher's site
OBJECTIVE: In an attempt for better treatment of bacterial infections and burn wounds, semisolid formulations containing norfloxacin (NF) and natural wound healing agent Curcuma longa were prepared. The rationale behind employing combination of NF and Curcuma longa is to obtain synergistic wound healing effect. The prepared formulations were compared with silver sulfadiazine cream 1%, USP. MATERIALS AND METHODS: Various ointments containing NF and C. longa were prepared using standard procedures. These formulations were evaluated for antimicrobial activity against various strains of aerobic and anaerobic microorganisms. The wound healing property was evaluated by histopathological examination and by measuring the wound contraction. RESULTS: The significant antimicrobial and wound healing effects were demonstrated by formulations which are comparable with silver sulfadiazine 1% cream (P < 0.05). Various morphological changes were observed by histopathology during the study period (days 1, 4, 8, and 12) which also supported the wound healing process. CONCLUSION: Based on the observed antimicrobial and wound healing effects, the formulations containing combination of NF and Curcuma longa could be employed as an alternative to commercial silver sulfadiazine 1% cream. This innovative mode of formulation can be employed for making burn wound healing process more effective.
Dua, K, Sheshala, R, Ling, TY, Hui Ling, S & Gorajana, A 2013, 'Anti-inflammatory, antibacterial and analgesic potential of cocos nucifera linn.: a review.', Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, vol. 12, no. 2, pp. 158-164.View/Download from: Publisher's site
At present, approximately 25%of drugs in modern pharmacopoeia are derived from plant sources (phytomedicines) that can be developed for the treatment of diseases and disorders. Many other drugs are synthetic analogues built on the prototype compounds isolated from plants. Cocos nucifera Linn. (Arecaceae), which is commonly known as coconut, is a plant possessing a lot of potential as an ingredient in traditional medicines for the treatment of metabolic disorders and particularly as an anti-inflammatory, antimicrobial and analgesic agent. This review emphasizes on the recent literature and research findings that highlight the significant biological activities of C. nucifera Linn. such as its anti-inflammatory, antimicrobial and analgesic properties. This review can help researchers keen on exploiting the therapeutic potential of C. nucifera Linn. which may motivate them to further explore their commercial viability.
Madan, J, Kadam, V, Bandavane, S & Dua, K 2013, 'Formulation and evaluation of microspheres containing ropinirole hydrochloride using biodegradable polymers', Asian Journal of Pharmaceutics, vol. 7, no. 4, pp. 184-188.View/Download from: Publisher's site
The present work relates with developing long acting sustain release microspheres of ropinirole hydrochloride (RPN) for treatment of Parkinson's disease, that will sustain drug release up to 1 month. Biodegradable microspheres of RPN were prepared by using two different polymers (poly lactic co glycolic acid [PLGA] 50:50 and PLGA 75:25) employing double emulsion (W/O/W) solvent evaporation method. Preliminary optimization of process parameter was done for concentration of polyvinyl alcohol (PVA) solution, stirring speed, temperature of PVA solution, ratio of the drug to polymer (D/P) and ratio of internal phase to external phase volume (IP/EP). All formulations were evaluated for particle size, percentage yield, entrapment efficiency (EE), shape etc. Formulation E3 and E4 shows maximum EE. % in vitro drug release per day of E3 and E4 batch was studied. The RPN was incorporated successfully in microspheres prepared with 0.5% w/v PVA at 8000 RPM stirring speed, 20°C processing temperature, 1:4 drug polymer ratio and 1:30 IP/EP ratio, which provides sustained release up to 4 weeks with better efficacy and patient compliance and can be employed as an alternative to existing oral medications.
Madan, JR, Sagar, B, Chellappan, DK & Dua, K 2013, 'Development and evaluation of transdermal organogels containing nicorandil.', Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, vol. 12, no. 3, pp. 246-252.View/Download from: Publisher's site
The objective of the study was to formulate a transdermal product containing Nicorandil as a model drug, because it has been first drug of choice to treat angina and hypertension. A further objective was to reduce its side effects. The transdermal product was prepared using various synthetic and natural gelling agents such as Carbopol 934p, Carbopol 974p, HPMC K15M and HPMC K100M. Various penetration enhancers were incorporated to enhance the diffusion across the rat skin. A further objective was to formulate organogels and minimize the concentration of penetration enhancer to 50% of the concentration used in gels and yet to achieve the maximum drug release. The prepared formulations were evaluated for their physical appearance, viscosity, spreadability, drug content and freeze thaw cycle. Based on in vitro studies across rat skin and human cadaver skin it was concluded that Nicrorandil transdermal organogel formulation using HPMC K100M with 2% w/w Transcutol-P shows increase in cumulative diffusion of Nicorandil amongst all other formulations.
Sheshala, R, Ying, LT, Hui, LS, Barua, A & Dua, K 2013, 'Development and anti-microbial potential of topical formulations containing Cocos nucifera Linn.', Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry, vol. 12, no. 3, pp. 253-264.View/Download from: Publisher's site
In order to achieve better treatment for local wounds and bacterial infections, topical formulations containing Cocos nucifera Linn. were developed. These formulations were evaluated for their physicochemical properties and antimicrobial efficacy against various strains of microorganisms. Semisolid formulations containing 5% w/w of Cocos nucifera Linn. were prepared by employing different dermatological bases and were evaluated for their physical appearance, pH, rheological properties, FTIR-spectroscopic analysis, thermodynamic stability and stability studies. The antimicrobial activity of each prepared formulation was determined using disk-diffusion method against various strains of microorganisms. All the prepared formulations were found to be stable and exhibited suitable physicochemical characteristics including pH, viscosity and spreadability which are necessary for an ideal topical preparation, in addition to strong antimicrobial activity. Carbopol gel base was found to be the most suitable dermatological base for Cocos nucifera Linn. in comparsion to other bases. Cocos nucifera Linn. formulations showed great potential for wounds and local bacterial infections. Moreover, carbopol gel base with its aesthetic appeal was found to be a suitable dermatological base for Cocos nucifera Linn. semisolid formulation as it had demonstrated significant physicochemical properties and greater diffusion when assessed using disk- diffusion method.
Dua, K, Leong, NK, Kaur, M, Bin, LW, Azman, K & Gorajana, A 2012, 'Preparation, physicochemical evaluation and antimicrobial potential of topical dosage forms containing natural anti-inflammatory agent, Curcuma longa', Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry, vol. 10, no. 6, pp. 452-462.View/Download from: Publisher's site
In an attempt for better treatment of bacterial infections and burn wounds various topical formulations containing 1%w/w of Curcuma longa were prepared and evaluated for physical appearance, pH, rheological properties and stability studies. Antimicrobial activity of prepared formulations was found to be more effective against various strains of bacteria. Carbopol gel base is the most suitable dermatological base for Curcuma longa in comparison to various other dermatological bases. It also has aesthetic appeal, which other bases lack, an important aspect from patient compliance and consumer point of view. The therapeutic potential of such topical formulations may motivate researchers for its further exploitation so that it may be commercially viable. This innovative mode of formulation of Curcuma longa can be employed for enhancing the anti-microbial effect. © 2011 Bentham Science Publishers.
Dua, K, Pabreja, K & Gorajana, A 2012, 'Dissolution behaviour of aceclofenac-PVP coprecipitates', ARS PHARMACEUTICA, vol. 53, no. 3, pp. 7-12.
Gorajana, A, Rajendran, A, Dua, K, Pabreja, K & Hoon, TP 2012, 'Preparation, Characterization, and In Vitro Evaluation of Nitrendipine Solid Dispersions', JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY, vol. 33, no. 5, pp. 676-684.View/Download from: Publisher's site
Ramana, MV, Dua, K, Himaja, M & Pabreja, K 2012, 'Preparation and characterization of solid dispersions of Rofecoxib', Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry, vol. 10, no. 6, pp. 393-398.View/Download from: Publisher's site
The present study is aimed at improving the dissolution of poorly soluble drug, rofecoxib, using solid dispersion technique. The solid dispersions were prepared in different proportions using hydrophilic carriers like mannitol, and urea. The dissolution rate studies were performed in both simulated gastric fluid and simulated intestinal fluid. It is observed that the dissolution was affected by the acidity of the medium. Solid dispersions gave faster dissolution rate when compared to corresponding physical mixture and pure drug. In vivo absorption and anti-inflammatory activity studies of solid dispersions also confirmed the above results. The DSC thermogram and IR spectra revealed that there is no interaction of Rofecoxib with additives and the drug, rofecoxib is stable in solid dispersions. © 2011 Bentham Science Publishers.
Dua, K & Pabreja, K 2011, 'Investigation on Dissolution Pattern and Mathematical Modeling of Drug Release of UDCA by Complextaion with b-Cyclodextrin-Choline Dichloride Coprecipitate', Journal of liver, vol. 1, no. 1, pp. 1-10.View/Download from: Publisher's site
The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in β-cyclodextrin (β-CD) on in vitro dissolution of Ursodeoxycholic acid (UDCA) from molecular inclusion complexes. The molecular inclusion complexes of UDCA with β-CD coprecipitated with CDC were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures and cyclodextrin inclusion complexes (UDCA-β-CD- CDC) were carried out. Molecular inclusion complexes of Ursodeoxycholic acid with coprecipitated β-CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH1.2 and phosphate buffer, pH 7.4. Inclusion complexes with 1:2M ratio showed maximum dissolution rate in comparison to other ratios. FT-IR spectroscopy and differential scanning calorimetry studies indicated no interaction between UDCA and β-CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of β-CD. The in vitro release from all the formulations was best described by first order kinetics followed by Higuchi release model. In conclusion, dissolution of Ursodeoxycholic acid can be enhanced by using the β-CD-CDC coprecipitate as a host st molecolec.
Dua, K, Pabreja, K & Ramana, MV 2011, 'Enhancement of Dissolution Behavior of Aceclofenac by Complexation with beta-Cyclodextrin-Choline Dichloride Coprecipitate', JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY, vol. 32, no. 10, pp. 1477-1484.View/Download from: Publisher's site
Dua, K, Pabreja, K, Ramana, MV & Bukhari, NI 2011, 'Preparation, Characterization, and In Vitro Evaluation of Aceclofenac PVP-Solid Dispersions', JOURNAL OF DISPERSION SCIENCE AND TECHNOLOGY, vol. 32, no. 8, pp. 1151-1157.View/Download from: Publisher's site
Dua, K, Pabreja, K, Ramana, MV & Lather, V 2011, 'Dissolution behavior of β-cyclodextrin molecular inclusion complexes of aceclofenac', Journal of Pharmacy and Bioallied Sciences, vol. 3, no. 3, pp. 417-425.View/Download from: Publisher's site
The objective of the present investigation was to study the effect of-cyclodextrin (-CD) on the in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. Aceclofenac molecular inclusion complexes in 1:1 and 1:2 M ratio were prepared using a kneading method. The in vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes was carried out. Molecular inclusion complexes of AF with-CD showed a considerable increase in the dissolution rate in comparison with the physical mixture and pure drug in 0.1 N HCl, pH 1.2, and phosphate buffer, pH 7.4. Inclusion complexes with a 1:2 M ratio showed the maximum dissolution rate in comparison to other ratios. Fourier transform infrared spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and-CD in complexes in solid state. Molecular modeling results indicated the relative energetic stability of the-CD dimer-AF complex as compared to-CD monomer-AF. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with-CD. The in vitro release from all the formulations was best described by first-order kinetics (R 2 = 0.9826 and 0.9938 in 0.1 N HCl and phosphate buffer, respectively) followed by the Higuchi release model (R 2 = 0.9542 and 0.9686 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, the dissolution of AF can be enhanced by the use of a hydrophilic carrier like-CD.
Lyn, LY, Sze, HW, Rajendran, A, Adinarayana, G, Dua, K & Garg, S 2011, 'Crystal modifications and dissolution rate of piroxicam.', Acta Pharm, vol. 61, no. 4, pp. 391-402.View/Download from: Publisher's site
Piroxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility which exhibits polymorphism. The present study was carried out to develop polymorphs of piroxicam with enhanced solubility and dissolution rate by the crystal modification technique using different solvent mixtures prepared with PEG 4000 and PVP K30. Physicochemical characteristics of the modified crystal forms of piroxicam were investigated by X-ray powder diffractometry, FT-IR spectrophotometry and differential scanning calorimetry. Dissolution and solubility profiles of each modified crystal form were studied and compared with pure piroxicam. Solvent evaporation method (method I) produced both needle and cubic shaped crystals. Slow crystallization from ethanol with addition of PEG 4000 or PVP K30 at room temperature (method II) produced cubic crystal forms. Needle forms produced by method I improved dissolution but not solubility. Cubic crystals produced by method I had a dissolution profile similar to that of untreated piroxicam but showed better solubility than untreated piroxicam. Cubic shaped crystals produced by method II showed improved dissolution, without a significant change in solubility. Based on the XRPD results, modified piroxicam crystals obtained by method I from acetone/benzene were cube shaped, which correlates well with the FTIR spectrum; modified needle forms obtained from ethanol/methanol and ethanol/acetone showed a slight shift of FTIR peak that may be attributed to differences in the internal structure or conformation.
Pabreja, K, Dua, K & Gorajana, A 2011, 'Evaluation of topical gels containing ketorolac tromethamine on inflammation and hyperalgesia in rats', Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry, vol. 10, no. 5, pp. 323-326.View/Download from: Publisher's site
Over recent years, non-steroidal anti-inflammatory drugs (NSAIDs) have been increasingly introduced as topical preparations as they are simple to apply and deliver high drug concentrations locally with limited side effects. Ketorolac trometamol (KT), a potent COX-2 inhibitor, produces typical side effects of NSAIDs when given orally and systemically. Hence the present investigation encompasses the development of topical formulations employing different dermatological bases and evaluated for its efficacy and safety. Standard procedures were followed to test the anti-inflammatory and antihyperalgesic effects in male Wistar albino rats. Amongst the various semisolid formulations, the formulation containing hydroalcoholic carbopol gel base (KT 1 ) was found to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation (79.69±1.51 after 5 h of carrageenan administration) as compared to formulation containing plain carbopol gel base (68.75±2.76) and PEG base 73.44±1.23. This demonstrates the suitability of carbopol gel base as an ideal dermatological base for ketorolac trometamol topical formulation and thus providing an ample credence for better therapeutic efficacy. © 2011 Bentham Science Publishers.
Pabreja, K, Dua, K, Sharma, S, Padi, SSV & Kulkarni, SK 2011, 'Minocycline attenuates the development of diabetic neuropathic pain: possible anti-inflammatory and anti-oxidant mechanisms.', Eur J Pharmacol, vol. 661, no. 1-3, pp. 15-21.View/Download from: Publisher's site
Painful neuropathy, a common complication of diabetes mellitus is characterized by allodynia and hyperalgesia. Recent studies emphasized on the role of non-neuronal cells, particularly microglia in the development of neuronal hypersensitivity. The purpose of the present study is to evaluate the effect of minocyline, a selective inhibitor of microglial activation to define the role of neuroimmune activation in experimental diabetic neuropathy. Cold allodynia and thermal and chemical hyperalgesia were assessed and the markers of inflammation and oxidative and nitrosative stress were estimated in streptozotocin-induced diabetic rats. Chronic administration of minocycline (40 and 80 mg/kg, i.p.) for 2 weeks started 2 weeks after diabetes induction attenuated the development of diabetic neuropathy as compared to diabetic control animals. In addition, minocyline treatment reduced the levels of interleukin-1β and tumor necrosis factor-α, lipid peroxidation, nitrite and also improved antioxidant defense in spinal cords of diabetic rats as compared to diabetic control animals. In contrast, minocycline (80 mg/kg, per se) had no effect on any of these behavioral and biochemical parameters assessed in age-matched control animals. The results of the present study strongly suggest that activated microglia are involved in the development of experimental diabetic neuropathy and minocycline exerted its effect probably by inhibition of neuroimmune activation of microglia. In addition, the beneficial effects of minocycline are partly mediated by its anti-inflammatory effect by reducing the levels of proinflammatory cytokines and in part by modulating oxidative and nitrosative stress in the spinal cord that might be involved in attenuating the development of behavioral hypersensitivity in diabetic rats.
Dua, K, Pabreja, K & Ramana, MV 2010, 'Comparative Investigation on in vitro release of extemporaneously prepared norfloxacin semisolid formulations with marketed silver sulfadiazine 1% cream, USP using model independent approach', Ars Pharmaceutica, vol. 51, no. 4, pp. 177-185.
Objective: In an attempt for better treatment of bacterial infections, various semisolid formulations containing 5% w/w of norfloxacin were prepared and evaluated for in vitro drug release and in vitro skin permeability using dialysis membrane and rat abdominal skin respectively. The in vitro diffusion and permeation profile of the prepared formulation was compared with marketed silver sulfadiazine cream 1%, USP using model independent approach. Methods: Various semisolid formulations were prepared with different dermatological bases using standard procedures. In vitro diffusion and permeation studies were carried out using Keshary-Chein (KC) type diffusion cell using dialysis membrane and rat abdominal skin respectively. Results: The f1 lower than 15 and f2 higher than 50 indicated similarities in the in vitro diffusion and permeation profiles of the extemporaneously prepared selected semisolid formulations and marketed silver sulfadiazine 1% cream, USP. Conclusion: Amongst all the semisolid formulations prepared, carbopol gel base was found to be most suitable dermatological base for norfloxacin, the results obtained for in vitro diffusion, and in vitro skin permeation studies are comparable with that of marketed silver sulphadiazine 1% cream, USP.
Mpharm, KD, Ramana, MV, Sara, UVS, Agrawal, DK, Mpharm, KP & Chakravarthi, S 2010, 'Preparation and evaluation of transdermal plasters containing norfloxacin: a novel treatment for burn wound healing.', Eplasty, vol. 10, p. e44.
OBJECTIVE: In an attempt for better treatment of bacterial infections and burn wounds, plaster formulations containing different concentrations of norfloxacin were prepared using polymers like polyvinylpyrrolidone and polyvinyl alcohol and evaluated for physicochemical parameters, in vitro drug release, antimicrobial activity, and burn wound healing properties. The prepared formulations were compared with silver sulfadiazine cream 1%, USP. METHODS: Plaster formulations containing different concentrations of norfloxacin were prepared by solvent casting method using combination of polymers like polyvinylpyrrolidone and polyvinyl alcohol. These plasters were characterized for drug content, thickness, percentage elongation, tensile strength, in vitro drug release properties, and antimicrobial activity against various strains of aerobic and anaerobic microorganisms. The wound healing property was evaluated by histopathological examination and by measuring the wound contraction. RESULTS: The in vitro release and in vitro skin permeation followed the first-order kinetics followed by diffusion as dominant release mechanism. In spite of the significant antimicrobial and wound healing effects produced by plasters, the observed values were less than the values obtained with silver sulfadiazine 1% cream (P < .05). Various histopathological changes observed during the study period (days 1, 4, 8, and 12) also supported the wound healing process. CONCLUSION: Based on the observed in vitro performances along with antimicrobial and wound healing effects, the 5% norfloxacin transdermal plasters could be employed as an alternative to commercial silver sulfadiazine 1% cream.
Pabreja, K, Dua, K & Padi, SSV 2010, 'Evaluation of extemporaneously manufactured topical gels containing aceclofenac on inflammation and hyperalgesia in rats', Current Drug Delivery, vol. 7, no. 4, pp. 324-328.View/Download from: Publisher's site
The systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) which act by inhibiting cyclooxygenase (COX) is severely hampered by gastric and peptic ulcers. The topical delivery of NSAIDs has the advantages of avoiding gastric and peptic ulcers and delivering the drug to the inflammation site. Importance of aceclofenac as a new generational NSAID has inspired the development of topical dosage forms. This mode of administration may help to avoid typical side effects of NSAIDs associated with oral and systemic administration such as gastric irritation, particularly diarrhoea, nausea, abdominal pain and flatulence. The aim of this study was to formulate topical gel containing 1% of aceclofenac in carbopol and PEG base and to evaluate it for analgesic and antiinflammatory activity using carrageenan-induced thermal hyperalgesia and paw oedema in rats. Carrageenan administration into the hind paw produced a significant inflammation associated with hyperalgesia as shown by decreased rat paw withdrawal latency in response to a thermal stimulus (47±0.5°C) 4 h after carrageenan injection. Topical application of AF1 significantly attenuated the development of hypersensitivity to thermal stimulus as compared to control (P<0.05) and other formulation treated groups (P<0.05). All the AF semisolid formulations, when applied topically 2 h before carrageenan administration, inhibited paw edema in a timedependent manner with maximum percent edema inhibition of 80.33±2.52 achieved with AF1 after 5 h of carrageenan administration However, topical application of AF2 markedly prevented the development of edema as compared to other formulation (AF2 and AF3) treated groups (P<0.05). Among all the semisolid formulations, Carbopol gel base was found to be most suitable dermatological base for aceclofenac. © 2010 Bentham Science Publishers Ltd.
Dua, K, Sharma, VK, Ramana, MV, Sara, UVS & Pabreja, K 2009, 'Developments in transdermal drug delivery', Australian Journal of Pharmacy, vol. 90, no. 1073, pp. 69-71.
Dua, K, Sharma, VK, Sara, UVS, Agarwal, DK & Ramana, MV 2009, 'Penetration enhancers for TDDS: A tale of the under skin travelers', Advances in Natural and Applied Sciences, vol. 3, no. 1, pp. 95-101.
The noninvasive route of delivery systems has many advantages over the conventional delivery systems. Although its applications are limited by low skin permeability and physicochemical properties of drugs The permeation of drugs through skin can be enhanced by various methods including phys ical methods such as iontophoresis (application of low level electric current), phonophoresis (use of ultra sound energy), eletroporation and by chemical penetration enhancers etc. The transdermal route has been recognized as one of the highly potential routes of systemic drug delivery and provides the advantage of avoidance of the first-pass effect, ease of use and withdrawal (in case of side effects), and better patient compliance. However, the major limitation of this route is the difficulty of permeation of drug through the skin. Studies have been carried out to find safe and suitable permeation enhancers to promote the percutaneous absorption of a number of drugs. The present review highlights various categories of penetration enhancers; the involved mechanism leading to a judicious s election of suitable penetration enhancers for improving the transdermal permeation of poorly absorbed drugs. © 2009, American Eurasian Network for Scientific Information.
Singh, SK, Kumar, Y, Kumar, SS, Sharma, VK, Dua, K & Samad, A 2009, 'Antimicrobial Evaluation of Mangiferin Analogues', INDIAN JOURNAL OF PHARMACEUTICAL SCIENCES, vol. 71, no. 3, pp. 328-U106.View/Download from: Publisher's site
Ramana, MV, Himaja, M, Dua, K, Sharma, VK & Pabreja, K 2008, 'A new approach: Enhancement of solubility of rofecoxib', Asian Journal of Pharmaceutics, vol. 2, no. 2, pp. 96-96.View/Download from: Publisher's site
Dua, K, Ramana, MV, Singh Sara, UV, Himaja, M, Agrawal, A, Garg, V & Pabreja, K 2007, 'Investigation of enhancement of solubility of norfloxacin β-cyclodextrin in presence of acidic solubilizing additives', Current Drug Delivery, vol. 4, no. 1, pp. 21-25.View/Download from: Publisher's site
The present study is aimed at improving the solubility of a poorly water-soluble drug, norfloxacin by incorporating solubilizing additives such as ascorbic acid and citric acid into the β-cyclodextrin complexes. Norfloxacin, being amphoteric in nature, exhibits a higher solubility at pH below 4 and above 8. Addition of substances like ascorbic acid and citric acid in β-cyclodextrin complexes reduces the pH of the immediate microenvironment of the drug below pH 4. In the present work, β-cyclodextrin complexes of norfloxacin were prepared along with solubilizing additives such as citric acid and ascorbic acid in various proportion and the dissolution profile was performed in both HCl buffer, pH 1.2 and phosphate buffer, pH 7.4. The results have shown an enhanced dissolution rate in both media. DSC and IR spectral studies performed on the solid complexes have shown that there is no interaction of the drug with the additives and â-cyclodextrin. Disc diffusion studies have shown larger diameters of zone of inhibition indicating a greater diffusivity of the drug into the agar medium. © 2007 Bentham Science Publishers Ltd.
Dua, K, Sara, UVS, Sharma, VK, Agrawal, A, Ramana, MV & HImaja, M 2007, 'Breaking the skin barrier: Newer developments in transdermal drug delivery', Australian Journal of Pharmacy, vol. 88, no. 1051, pp. 74-76.
Optimum therapeutic outcomes require not only proper drug selection but also effective drug delivery. The human skin is a readily accessible surface for drug delivery. Transdermal drug delivery - the delivery of drugs across the skin and into systemic circulation - is distinct from topical drug penetration, which targets local areas. Several new active transport technologies have been developed for the transdermal delivery. For example, microporation, medicated tattoos, needleless jet injectors, electrophoresis and phonophoresis are all being used to facilitate delivery of drugs across the epidermal barrier. However, only a few of these technologies are now commercially available. Various new technologies like microneedles in transdermal drug delivery also play a significant impact in the progress of this dermal technology.
Ramana, M, Chaudhari, A, Himaja, M, Satyanarayana, D & Dua, K 2007, 'An approach to minimize Pseudomembranous colitis caused by clindamycin through liposomal formulation', Indian Journal of Pharmaceutical Sciences, vol. 69, no. 3, pp. 390-393.View/Download from: Publisher's site
Liposomal encapsulation is known to significantly improve the therapeutic index of a drug. In the present investigation liposomal formulations were chosen to transport clindamycin, which is considered as the most effective topical antibiotic for acne, into the skin layers. Liposomes with clindamycin phosphate were prepared using lipid film hydration method and the optimum ratio of the components was determined. The liposomes were characterized for their vesicle size, shape, encapsulation efficiency, % drug content and for in vitro skin permeation study. The results suggest that the average size of vesicles was found to be in range of 4.91-6.75 μm. Highest encapsulation efficiency (45.4%) and in vitro skin permeation (62%) was achieved with a formulation containing drug: lipid: cholesterol in the ratio of 1:1:1. Liposomal formulation of clindamycin phosphate with good skin permeation properties was incorporated into gel base and comparison of in vitro skin permeation was made with non liposomal marketed gel, both containing 1% clindamycin phosphate. Higher rate of drug release across the rat abdominal skin was found with liposomal gel (54%) than non-liposomal marketed gel (48.7%). Biological study revealed that by encapsulating clindamycin phosphate into liposomes the occurrence of Pseudomembranous colitis could be reduced significantly in comparison to plain clindamycin phosphate.
Malipeddi, VR, Dua, K, Sara, UVS, Malipeddi, H & Agrawal, A 2006, 'Comparative evaluation of transdermal formulations of norfloxacin with silver sulfadiazine cream, USP, for burn wound healing property.', Journal of burns and wounds, vol. 5, p. e4.
OBJECTIVE:In an attempt to find a better treatment for bacterial infections and burn wounds, various semisolid formulations containing 5% w/w of norfloxacin were prepared and evaluated for physicochemical parameters, in vitro drug release through cellophane membrane, antimicrobial activity, and burn wound healing properties. The prepared formulations were compared with silver sulfadiazine 1% cream, USP. METHODS:Various semisolid formulations were prepared with different bases like Carbopol, polyethylene glycol, and hydroxypropylmethyl cellulose, using standard procedures. The antimicrobial activity of these semisolid norfloxacin formulations, against various strains of aerobic and anaerobic microorganisms, was evaluated by using a standard cup-plate method. The wound healing property was evaluated by measuring the wound contraction and expressed as percentage of contraction of original wound size for each animal group. RESULTS:Antimicrobial activity of norfloxacin semisolid formulations was found to be equally effective against both aerobic and anaerobic bacteria in comparison to a formulation of silver sulfadiazine 1% cream, USP, available on the market. CONCLUSION:The burn wound healing property of the prepared norfloxacin semisolid formulations was found to be in good agreement with silver sulfadiazine 1% cream, USP, available on the market.
Awasthi, R, Madan, JR, Malipeddi, H, Dua, K & Kulkarni, GT, 'Therapeutic strategies for targeting non-coding RNAs with special emphasis on novel delivery systems', Non-coding RNA Investigation, vol. 3, pp. 11-11.View/Download from: Publisher's site
Banerjee, A, Kumar, R, Gulati, M, Singh, SK, Dua, K, Singh, G, Sharma, PK & Sharma, A 2021, 'Self-Emulsifying Drug Delivery Systems: A Strategy to Improve the Bioavailability of Hydrophobic Drugs' in The Era of NanotechnologyEmergence and Essentials, Apple Academic Press, USA, pp. 22-34.
Hinge, N, Pandey, MM, Singhvi, G, Gupta, G, Mehta, M, Satija, S, Gulati, M, Dureja, H & Dua, K 2020, 'Nanomedicine advances in cancer therapy' in Advanced 3D-Printed Systems and Nanosystems for Drug Delivery and Tissue Engineering, Elsevier, pp. 219-245.
The book highlights the most recent advances in both nanosystems and 3D-printed systems for both drug delivery and tissue engineering applications.
Mahmood, A, Singhvi, G, Manchanda, P, Pandey, MM, Dubey, SK, Gupta, G, Chellappan, DK, Seyfoddin, A & Dua, K 2020, 'Applications of 3D printing for the advancement of oral dosageforms' in Advanced 3D-Printed Systems and Nanosystems for Drug Delivery and Tissue Engineering, Elsevier, pp. 39-53.
The book highlights the most recent advances in both nanosystems and 3D-printed systems for both drug delivery and tissue engineering applications.
Pont, L, Dua, K & Williams, K 2020, 'Drug Delivery of Respiratory Medicines in Practice' in Dua, K (ed), Targeting Chronic Inflammatory Lung Diseases Using Advanced Drug Delivery Systems, Academic Press Elsevier, United Kingdom, pp. 33-38.
Ghadiri, M, Yung, AE & Haghi, M 2020, 'Role of Oxidative Stress in Complexity of Respiratory Diseases' in Maurya, P & Dua, K (eds), Role of Oxidative Stress in Pathophysiology of Diseases, Springer Nature.
Mehta, M, Sharma, P, Kaur, S, Dhanjal, DS, Singh, B, Vyas, M, Gupta, G, Chellappan, DK, Nammi, S, Singh, TG, Dua, K & Satija, S 2020, 'Plant-based drug delivery systems in respiratory diseases' in Dua, K, Hansbro, P, Wadhwa, R, Haghi, M, Pont, L & Williams, K (eds), Targeting Chronic Inflammatory Lung Diseases Using Advanced Drug Delivery Systems, Academic Press Elsevier, United Kingdom, pp. 517-530.
Zeeshan, F & Dua, K 2020, 'Pharmacokinetics and pharmacodynamics of the advanced drug delivery systems' in Dua, K, Hansbro, P, Wadhwa, R, Haghi, M, Pont, L & Williams, K (eds), Targeting Chronic Inflammatory Lung Diseases Using Advanced Drug Delivery Systems, Academic Press Elsevier, United Kingdom, pp. 551-566.
Gupta, G, Wadhwa, R, Pandey, P, Singh, SK, Gulati, M, Satija, S, Mehta, M, Singh, AK, Dureja, H, Collet, T, Pabreja, K, Chellappan, DK & Dua, K 2020, 'Obesity and Diabetes: Pathophysiology of Obesity-Induced Hyperglycemia and Insulin Resistance' in Pathophysiology of Obesity-Induced Health Complications, pp. 81-97.View/Download from: Publisher's site
Hinge, N, Pandey, MM, Singhvi, G, Gupta, G, Mehta, M, Satija, S, Gulati, M, Dureja, H & Dua, K 2020, 'Nanomedicine advances in cancer therapy' in Advanced 3D-Printed Systems and Nanosystems for Drug Delivery and Tissue Engineering, Elsevier, pp. 219-253.View/Download from: Publisher's site
Mahmood, A, Singhvi, G, Manchanda, P, Pandey, MM, Dubey, SK, Gupta, G, Chellappan, DK, Seyfoddin, A & Dua, K 2020, 'Applications of 3D printing for the advancement of oral dosage forms' in Advanced 3D-Printed Systems and Nanosystems for Drug Delivery and Tissue Engineering, Elsevier, pp. 39-57.View/Download from: Publisher's site
Pandey, P, Mehta, M, Shukla Shakti, Wadhwa, R, Singhvi, G, Chellappan, DK, Satija, S, Gupta, G, Awasthi, R, Prasher, P, Hansbro, P, Dua, K & Dureja, H 2020, 'Emerging Nanotechnology in Chronic Respiratory Diseases' in Talegaonkar, S & Rai, M (eds), Nanoformulations in Human Health: Challenges and Approaches, Springer, Cham, pp. 449-468.View/Download from: Publisher's site
Pandey, P, Mehta, M, Shukla, S, Wadhwa, R, Singhvi, G, Chellappan, DK, Satija, S, Gupta, G, Awasthi, R, Prasher, P, Hansbro, PM, Dua, K & Dureja, H 2020, 'Emerging Nanotechnology in Chronic Respiratory Diseases' in Nanoformulations in Human Health, Springer International Publishing, pp. 449-468.View/Download from: Publisher's site
Singh, L, Majhi, S, Pabreja, K, Negi, P, Goyal, R, Gupta, G, Chellappan, DK & Dua, K 2020, 'Oxidative Stress in Liver Disease' in Role of Oxidative Stress in Pathophysiology of Diseases, Springer Nature, Singapore, pp. 209-228.View/Download from: Publisher's site
Liver, being the second largest organ, maintains homeostasis by undergoing a number of risk factors that include alcohol, drugs, environmental pollutants, and radiation. All these factors are capable of inducing oxidative stress by generating free radicals that eventually result in various forms of severe liver diseases. In this chapter, the consequences of oxidative stress are studied, along with its pathophysiology, its effects on organelles, physiological alterations, and the common diseases that occur due to oxidative stress. The progression of various liver diseases primarily involves lipid peroxidation, deoxyribonucleic acid (DNA) damage, signaling of inflammatory mediators, and ultimately generation of free radicals. The inarguable role of prooxidants in hepatic pathogenesis can be evidenced by an increase in the levels of biomarkers of oxidative stress, namely, malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), to name a few. These markers are paralleled by utilizing endogenous antioxidant mechanisms, thus decreasing the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and glutathione (GSH).
This challenge was overcome by a diverse and rapid development in the field of biomarkers and antioxidants. Newer advances in the field of biomarkers outlined strategies to identify diseases at an early stage so that the treatment procedure could be both clinically useful and cost-effective. Advanced research on antioxidants, to treat liver disease, resulted in the emergence of natural substances that contain common natural herbal extracts, vitamins, and other compounds. Antioxidant use, either as a single compound or in combination, has become key molecules today for counteracting our stressed system and to achieve healthy homeostasis. However, new research should be carried out at cellular and molecular pharmacology levels in combination with drug targeting systems so as to get innovative ideas for the therapeutics of hepatic dis...
Wadhwa, R, Bharathala, S, Aggarwal, T, Sehgal, N, Kumar, N, Gupta, G, Chellappan, DK, Maurya, PK, Pinto, TDJA, Collet, T, Dureja, H, Hansbro, PM & Dua, K 2020, 'Pulmonary Bioadhesive Drug Delivery Systems and Their Applications' in Bioadhesives in Drug Delivery, John Wiley & Sons, pp. 371-390.View/Download from: Publisher's site
This book addresses the various relevant aspects of bioadhesives in drug delivery in an easily accessible and unified manner.
Mucoadhesive based pulmonary drug delivery is an advanced novel intervention against several pulmonary diseases including asthma, chronic obstructive pulmonary disease, cystic fibrosis, etc. Mucoadhesive polymers are required to prolong the residence time of the drug to promote drug absorption via mucosa at a controlled rate in order to enhance the therapeutic effect. The drug interacts with the mucus layer and mucin molecules to prolong the residence time. Such a drug delivery system has low enzymatic degradation with improved patient compliance as its formulation depends on the use of a mucoadhesive and biocompatible polymer. Therefore, in this chapter, we have discussed the novel dosage formulations i.e. nanoparticles, liposomes, and microparticles for delivery via inhalation. However, there is an urgent need to study novel bioadhesive formulations with different polymeric materials and to identify many new drug molecules for pulmonary drug delivery.
Wadhwa, R, Sehgal, N, G, N, Aggarwal, T, Satija, S, Mehta, M, Gupta, G, Chellappan, DK, Tambuwala, MM, Oliver, B, Collet, T, Maurya, PK, Hansbro, PM & Dua, K 2020, 'Correction to: Oxidative Stress and Immunological Complexities in Multidrug-Resistant Tuberculosis' in Role of Oxidative Stress in Pathophysiology of Diseases, Springer Singapore, pp. C1-C1.View/Download from: Publisher's site
Wadhwa, R, Sehgal, N, G, N, Aggarwal, T, Satija, S, Mehta, M, Gupta, G, Chellappan, DK, Tambuwala, MM, Oliver, B, Collet, T, Maurya, PK, Hansbro, PM & Dua, K 2020, 'Oxidative Stress and Immunological Complexities in Multidrug-Resistant Tuberculosis' in Role of Oxidative Stress in Pathophysiology of Diseases, Springer Nature, Singapore, pp. 107-124.View/Download from: Publisher's site
Wadhwa, R, Aggarwal, T, Thapliyal, N, Chellappan, DK, Gupta, G, Gulati, M, Collet, T, Oliver, B, Williams, K, Hansbro, PM, Dua, K & Maurya, PK 2019, 'Nanoparticle-Based Drug Delivery for Chronic Obstructive Pulmonary Disorder and Asthma' in Nanotechnology in Modern Animal Biotechnology, Elsevier, The Netherlands, pp. 59-73.View/Download from: Publisher's site
Pulmonary diseases including chronic obstructive pulmonary disease (COPD) and asthma affect millions of people all over the world. Conventional treatment methodologies are not sufficient to cure or prevent the disease. With the advent of nanotechnology, drug delivery to specific target site is still challenging, but targeted delivery can be achieved by physiochemical properties of the nanoparticles. Delivery of nanoparticles, liposomes, dendrimers, and others has been extensively studied for successful delivery by inhalation and aerosols. Several factors such as size, density, surface, and physical-chemical properties of nanoparticle are essential to cross airway barriers. In this chapter, different nanoparticle-mediated drug delivery systems have been highlighted along with their applications and toxicity in COPD and asthma.
Wadhwa, R, Aggarwal, T, Thapliyal, N, Chellappan, DK, Gupta, G, Gulati, M, Collet, T, Oliver, B, Williams, K, Hansbro, PM, Dua, K & Maurya, PK 2019, 'Nanoparticle-Based Drug Delivery for Chronic Obstructive Pulmonary Disorder and Asthma' in Nanotechnology in Modern Animal Biotechnology, Elsevier, The Netherlands, pp. 59-73.View/Download from: Publisher's site
Pulmonary diseases including chronic obstructive pulmonary disease (COPD) and asthma affect millions of people all over the world. Conventional treatment methodologies are not sufficient to cure or prevent the disease. With the advent of nanotechnology, drug delivery to specific target site is still challenging, but targeted delivery can be achieved by physiochemical properties of the nanoparticles. Delivery of nanoparticles, liposomes, dendrimers, and others has been extensively studied for successful delivery by inhalation and aerosols. Several factors such as size, density, surface, and physical-chemical properties of nanoparticle are essential to cross airway barriers. In this chapter, different nanoparticle-mediated drug delivery systems have been highlighted along with their applications and toxicity in COPD and asthma.
Aggarwal, T, Wadhwa, R, Thapliyal, N, Gupta, R, Hansbro, PM, Dua, K & Maurya, PK 2019, 'Recent trends of nano-material as antimicrobial agents' in Nanotechnology in Modern Animal Biotechnology: Recent Trends and Future Perspectives, pp. 173-193.View/Download from: Publisher's site
© Springer Nature Singapore Pte Ltd. 2019. Nanomaterial has been employed as an alternative to antibiotics, diagnostic tools and delivery of therapeutics. In particular, nanomaterial has grabbed the attention of researchers due to their antimicrobial properties due to the emergence of multi-drug resistance of several micro-organisms. The present chapter highlights the antimicrobial nanomaterials with their mechanism of action along with their broad spectrum applications such as silver nanomaterial is antimicrobial in nature and is effective in drug delivery. Metallic, non-metallic and natural/ biodegradable nanomaterials have been discussed as potential antimicrobial and their mode of action. The mechanism of antimicrobial nanomaterial is poorly understood, but oxidative stress, non-oxidative action, inhibition of cell adhesion, decline in biofilm formation, obstructed quoram sensing and metal ion release are attributed to be as the major reasons. In addition, the limitation and toxicity with the clinical and environmental applications are also described.
Wadhwa, R, Shukla, SD, Chellappan, DK, Gupta, G, Collet, T, Hansbro, N, Oliver, B, Williams, K, Hansbro, PM, Dua, K & Maurya, PK 2019, 'Phytotherapy in Inflammatory Lung Diseases: An Emerging Therapeutic Interventional Approach' in Phytochemistry: An in-silico and in-vitro Update, Springer, Singapore, pp. 331-347.View/Download from: Publisher's site
Chronic obstructive pulmonary disease (COPD) and asthma are the most common inflammatory respiratory diseases related to an increase in mortality and morbidity. Generally, bronchodilators, ß- agonists, anticholinergics and theophylline used for treatment in these conditions and administered by inhalation for delivery, have localized and systematic effects. The adverse effects are due to pharmacodynamic and pharmacokinetic changes and especially drug-drug and drug-disease interactions. However, phytotherapy is classical and widespread throughout the world for the treatment of ailments. This chapter highlights cellular and molecular mediators involved in COPD and asthma, the shortcomings of current therapies and the emerging need of phytomedicines. Phytomedicine supports respiratory physiology, bronchial action and possesses antioxidants to maintain homeostasis.
Awasthi, R, Manchanda, S, Das, P, Velu, V, Malipeddi, H, Pabreja, K, D.J.A. Pinto, T, Gupta, G & Dua, K 2018, 'Poly(vinylpyrrolidone)' in Engineering of Biomaterials for Drug Delivery Systems Beyond Polyethylene Glycol, Woodhead Publishing, UK, pp. 255-269.
This book is a valuable resource for scientists and researchers in biomaterials, pharmaceuticals and nanotechnology, and all those who wish to broaden their knowledge in this field.
Awasthi, R, Singh, AK, Mishra, G, Maurya, A, Chellappan, DK, Gupta, G, Hansbro, PM & Dua, K 2018, 'An Overview of Circular RNAs' in Circular RNAs Biogenesis and Functions, Springer, Germany, pp. 3-14.View/Download from: Publisher's site
Circular RNAs (cirRNAs) are long, noncoding endogenous RNA molecules and covalently closed continuous loop without 5'–3' polarity and polyadenylated tail which are largely concentrated in the nucleus. CirRNA regulates gene expression by modulating microRNAs and functions as potential biomarker. CirRNAs can translate in vivo to link between their expression and disease. They are resistant to RNA exonuclease and can convert to the linear RNA by microRNA which can then act as competitor to endogenous RNA. This chapter summarizes the evolutionary conservation and expression of cirRNAs, their identification, highlighting various computational approaches on cirRNA, and translation with a focus on the breakthroughs and the challenges in this new field.
Dua, K, Sharma, VK & Sara, UVS 2018, 'Himachal Pradesh: An Insight into the Valley of Potential Medicinal Plants' in Himachal Pradesh Pharmaceutical Guide -2007, Bazaz Publications, pp. 29-33.
Kaurav, H, Manchanda, S, Dua, K & Kapoor, DN 2018, 'Nanocomposites in Controlled & Targeted Drug Delivery Systems' in Nano Hybrids and Composites, Trans Tech Publications, Switzerland, Switzerland, pp. 27-45.View/Download from: Publisher's site
In recent years, development of different types of nanocomposites have increased their utilization in the biomedical and pharmaceutical sciences. The nanometer size range and unique composition make nanocomposites a beneficial alternative to any single conventional material. The present chapter provides a general overview of nanocomposites, discusses different types of nanocomposites such as metal, ceramic and polymer nanocomposites. The discussion is further focused on different nanocomposite based controlled and targeted systems developed for delivery of various drugs including anti-cancer, anti-microbial, anti-inflammatory, anti-diabetic and cardiovascular drugs.
Wadhwa, R, Paudel, KR, Nee, TX, Xin Lau, NJ, Zeeshan, F, Madheswaran, T, Panneerselvam, J, Reddy, K, Hsu, A, Oliver, B, Hansbro, P, Chellappan, DK & Dua, K 2019, 'Preparation, characterisation and biological applications of Rutin loaded liquid crystalline nanoparticles in targeting airway diseases', Sydney New Horizons-2019.
de Souza Braga, M, Carvalho, GC, Dua, K, Gupta, G, Oliveira, A, Cerize, N & Pinto1, TJA 2018, 'Idarubicin loaded nanoparticles for breast cancer', World Congress on Recent Advances in Nanotechnology.View/Download from: Publisher's site
© 2019, Avestia Publishing. The development in targeted drug delivery involving nanotechnology is one of the leading research area in the treatment of cancer. The nanoparticles play a key role because of their efficiency in transporting, providing imaging markers and selective release of drugs and carrier systems . Anthracyclines, such as doxorubicin and idarubicin, are an important class of chemotherapeutic agents. Unfortunately, their efficacy in treating cancer is limited by a cumulative dose-dependent cardiotoxicity, which can cause irreversible heart failure . Particularly nanoparticle system has shown to be very promising for the improvement of the therapeutic effects of these, mainly due to the longer targeting and retention time in solid tumors, while minimizing systemic exposure, improving drug efficacy and reducing non-specific toxicity  . The objective of this work is to develop polymeric nanoparticles encapsulated with idarubicin. An aqueous solution of Idarubicin (1mM) was mixed with 45mL of poly(dimethylsiloxane)-graft-polyacrylates (0,1% w/v) with pH 8.2 for solubilisation. The sample was spray-dried using an atomization membrane with 4 μm of porosity. The particles were collected by an electrostatic chamber and characterized using a zeta-sizer and SEM. Drug release experiments were also carried out. The drug release was carried out in 0.1M HCl solution (pH 1.0) and phosphate buffer (pH 8.4, respectively in order to mimic the gastric and intestinal environment. It was observed a slower release in acidic pH as compared to alkaline pH. According to zeta-sizer data the particles have ±450 nm. SEM images showed that idarubicin was efficiently encapsulated. Drug-release studies are still on-going. Abstract: The development in targeted drug delivery involving nanotechnology is one of the leading research area in the treatment of cancer. The nanoparticles play a key role because of their efficiency in transporting, providing imaging markers an...
Starkey, M, Hanish, I, Dua, K, Nair, P, Haw, T, Hsu, A, Foster, P, Knight, D, Horvat, J, Wark, P & Hansbro, P 2014, 'Interleukin-13 predisposes mice to more severe influenza infection by suppressing interferon responses and activating microRNA-21/PI3K', CYTOKINE, 2nd Annual Meeting of the International-Cytokine-and-Interferon-Society (ICIS), ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, Melbourne, AUSTRALIA, pp. 70-70.View/Download from: Publisher's site
Dua, K 2020, 'Interview by the Nanomed Zone-A peek behind the paper – Kamal Dua on miRNA nanotherapeutics: potential and challenges in respiratory disorders-; https://www.nanomedzone.com/covid-19-a-peek-behind-the-paper-kamal-dua-…', Future Medicine, Future Science Group, UK, London, N3 1QB, UK.
Dua, K, Tambuwala, M, McCarron, P, Chellappan, DK & Gupta, G 2020, 'Interview by the Bioanalysis Zone; Ask the Experts: how business continued through the COVID-19 pandemic; https://www.bioanalysis-zone.com/2020/07/23/ask-experts-business-contin…', Future Science Group., UK.