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 Excellence Award in Pharmacy (2018), Young Scientist Award (2011), International Association for Dental Research Southeast Asian Division (IADR SEA); 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’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 450 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; Hacettepe University, Turkey; University Sao Paulo, Brazil; Western Sydney University, 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 a pharmaceutical and formulation scientist who recognized that there was limited information linking knowledge of various biological (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 and biological advances.
Dr Dua studied immunology under the supervision of Professor Phil Hansbro, an internationally recognised research leader in the area of respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). Working with Professor Phil 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 their novel findings into new, effective and patient complaint drug delivery systems suitable for maximal efficacy. Dr.Dua’s overall skills and expertise in formulation development combines with his in-depth knowledge of immunology to provide increased opportunities to expand 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)
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.
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.
Bugno, A, Almodovar, AAB, Saes, DPS, Awasthi, R, Ghisleni, DDM, de Souza Braga, M, de Oliveira, WA, Dua, K & de Jesus Andreoli Pinto, T 2018, 'Evaluation of an Amplified ATP Bioluminescence Method for Rapid Sterility Testing of Large Volume Parenteral', Journal of Pharmaceutical Innovation.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.
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: UTS OPUS or 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.
Andrade, LDO, Awasthi, R, Dua, K & de Jesus Andreoli Pinto, T 2018, 'Matrix-assisted laser desorption ionization-time of flight mass spectrometry for identification of bacteria isolated from pharmaceutical clean rooms.', Interventional Medicine & Applied Science, vol. 10, no. 1, pp. 45-53.View/Download from: UTS OPUS or Publisher's site
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.
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: UTS OPUS or 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: UTS OPUS or 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, Yap, WS, Bt Ahmad Suhaimi, NA, 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
The prevalence of type 2 diabetes mellitus (T2DM) has been increasing at an alarming rate. With an increased understanding of the pathophysiology and pathogenesis of T2DM, various new therapeutic options have been developed to target different key defects in T2DM. Incremental innovations of existing therapies either through unprecedented drug combinations, modified drug molecules, or improved delivery systems are capable to nullify some of the undesirable side effects of traditional therapies as well as to enhance effectiveness. The existing administration routes include inhalation, nasal, buccal, parenteral and oral. Newer drug targets such as protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), sirtuin (SIRT), and others are novel approaches that act via different mechanisms and possibly treating T2DM of distinct variations and aetiologies. Other therapies such as endobarrier, gene therapy, and stem cell technology utilize advanced techniques to treat T2DM, and the potential of these therapies are still being explored. Gene therapy is plausible to fix the underlying pathology of T2DM instead of using traditional reactive treatments, especially with the debut of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated protein9 (CRISPR-Cas9) gene editing tool. Molecular targets in T2DM are also being extensively studied as it could target the defects at the molecular level. Furthermore, antibody therapies and vaccinations are also being developed against T2DM; but the ongoing clinical trials are relatively lesser and the developmental progress is slower. Although, there are many therapies designed to cure T2DM, each of them has their own advantages and disadvantages. The preference for the treatment plan usually depends on the health status of the patient and the treatment goal. Therefore, an ideal treatment should take patient's compliance, efficacy, potency, bioavailability, and other pharmacological and non-pharmacological proper...
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 & formulation.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, 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, 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
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: UTS OPUS or 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 of 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
Auricularia polytricha is a popular mushroom found all over the world. In this study we considered the effect of an aqueous extract of A. polytricha (AEAP) on restoring sexual performance parameters to normal, evaluated by considering observations of sexual behavior. At 0, 6, 12, 18, and 24 days, the following parameters of sexual performance were identified before and throughout the observations: mount latency, intromission latency, ejaculation latency, mounting frequency, intromission frequency, ejaculation frequency, and postejaculatory interval. Treatment of rats under stress with AEAP showed promising effects on overcoming stress-induced sexual dysfunction, on sexual performance, and on accessory sexual organs and body weight. Mounting latency, intromission latency, ejaculation latency, and postejaculatory interval parameters were significantly decreased by AEAP, whereas mounting frequency, intromission frequency, and ejaculation frequency were significantly increased by AEAP. These properties were identified in sexually dynamic and indolent male rats. We conclude that AEAP has a potent aphrodisiac activity.
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: UTS OPUS or 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 PPAR, PPAR/, and PPAR. PPAR is the most extensively studied subtype of PPAR. There has been interesting preliminary evidence suggesting that diabetic patients receiving PPAR 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 PPAR in glioblastoma are summarized.
Gupta, G, Tiwari, J, Dahiya, R, Kumar Sharma, R, Mishra, A & Dua, K 2018, 'Recent updates on neuropharmacological effects of luteolin.', EXCLI journal, vol. 17, pp. 211-214.View/Download from: UTS OPUS or Publisher's site
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: UTS OPUS or 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...
Mohanta, S, Singh, SK, Kumar, B, Gulati, M, Kumar, R, Yadav, AK, Wadhwa, S, Jyoti, J, Som, S, Dua, K & Pandey, NK 2018, '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.
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: UTS OPUS or 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.
Singh, Y, Gupta, G, Sharma, R, Matta, Y, Mishra, A, Pinto, TDJA & 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
The proliferative cell process that causes prostate enlargement, obstruction of the bladder outlet, and lower urinary tract symptoms (LUTS) is known as benign prostatic hyperplasia (BPH). The prevalence of BPH worldwide is approximately 10%, 20%, 50%, and 80% for men in their 30s, 40s, 60s, and 70s, respectively. Recent data have revealed that overactivation of the renin angiotensin aldosterone system increases the level of bioactive peptide hormone angiotensin II, which downregulates the ACE2-angiotensin 1-7/Mas receptor axis path and upregulates angiotensin receptor type 1-mediated signaling, which finally leads to a proliferation of cellular elements in the prostate. We have hypothesized the mechanism that reverses the downregulation of the ACE2-angiotensin 1-7/Mas receptor axis path and the upregulation of angiotensin receptor type 1-mediated signaling. Thus, we posit that ACE2, Ang-(1-7), and the Mas receptor could be novel therapeutic targets for treating BPH/LUTS.
Singhvi, G, Manchanda, P, Krishna Rapalli, V, Kumar Dubey, S, Gupta, G & Dua, K 2018, 'MicroRNAs as biological regulators in skin disorders.', Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 108, pp. 996-1004.View/Download from: UTS OPUS or Publisher's site
microRNAs are being investigated as promising therapeutic targets and biomarkers for different disease conditions. miRNAs serve as essential regulators of cell differentiation, proliferation and survival. The involvement of miRNAs in the functioning and regulation of the skin cells and skin diseases is a rapidly advancing area in dermatological research. miRNAs have been identified to play a key role in the pathogenesis, diagnosis, and treatment of the skin diseases. Skin is one of the largest organs of the body, primarily functioning as the first line of defence against external insults including bacteria, virus and other pathogens. Various miRNAs have been identified to demonstrate significant effects in various skin inflammatory conditions such as wounds, cancer, psoriasis, scleroderma, dermatomyositis. The current review explores the possible roles of the miRNAs in skin disorders and reports relating to the clinical trials involving skin diseases and miRNAs. The review has also compiled the information of the databases available, which correlates the miRNAs with different diseases and give details about targeting interactions of miRNA.
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
One of the novel and progressive technology employed in pharmaceutical manufacturing, design of medical device and tissue engineering is three-dimensional (3D) printing. 3D printing technologies provide great advantages in 3D scaffolds fabrication over traditional methods in the control of pore size, porosity, and interconnectivity. Various techniques of 3D-printing include powder bed fusion, fused deposition modeling, binder deposition, inkjet printing, photopolymerization and many others which are still evolving. 3D-printing technique been employed in developing immediate release products, various systems to deliver multiple release modalities etc. 3D printing has opened the door for new generation of customized drug delivery with built-in flexibility for safer and effective therapy. Our mini-review provides a quick snapshot on an overview of 3D printing, various techniques employed, applications and its advancements in pharmaceutical sciences.
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: UTS OPUS or 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 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.
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: UTS OPUS or 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.
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
MicroRNAs (miRNAs) are short noncoding RNAs that control gene expression posttranscriptionally by directly blocking translation of their target mRNAs or by repressing protein production via mRNA destabilization. Investigations into miRNAs began approximately 12 years ago with their discovery in mammalian cells. Still, the involvement of miRNAs in the development of asthma remains unclear, and this topic needs further research to discover various molecular mechanisms responsible for the pathogenesis of asthma and new therapeutic interventions. So far, various miRNAs have been identified in allergic airway disease along with their targets. Our present mini-review highlights the latest information involving the role of miRNAs in asthma.
Dua, K, Rapalli, VK, 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 = Biomedecine & pharmacotherapie, vol. 107, pp. 1218-1229.View/Download from: UTS OPUS or Publisher's site
Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poor patient compliance, subsequently leading to treatment failure and development of antibiotic resistance. Notably, oxidative stress is a crucial underlying factor that adversely influences the various treatment regimens in tuberculosis. Little information is available with advanced drug delivery systems that could be effectively utilized, in particular, for targeting the oxidative stress in tuberculosis. Thus, this presents an opportunity to review the utility of various available, controlled-release drug delivery systems (e.g., microspheres, liposomes, niosomes, solid lipid nanoparticles, dendrimers) that could be beneficial in tuberculosis treatments. This will help the biological and formulation scientists to pave a new path in formulating a treatment regimen for multi-drug resistant Mtb.
Chellappan, DK, Sivam, NS, Teoh, KX, Leong, WP, Fui, TZ, Chooi, K, Khoo, N, 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 = Biomedecine & pharmacotherapie, vol. 108, pp. 1188-1200.View/Download from: UTS OPUS or Publisher's site
BACKGROUND:Type 1 diabetes mellitus (T1DM) is an autoimmune disorder characterized by T cell-mediated self-destruction of insulin-secreting islet cells. Management of T1DM is challenging and complicated especially with conventional medications. Gene therapy has emerged as one of the potential therapeutic alternatives to treat T1DM. This review primarily focuses on the current status and the future perspectives of gene therapy in the management of T1DM. A vast number of the studies which are reported on gene therapy for the management of T1DM are done in animal models and in preclinical studies. In addition, the safety of such therapies is yet to be established in humans. Currently, there are several gene level interventions that are being investigated, notably, overexpression of genes and proteins needed against T1DM, transplantation of cells that express the genes against T1DM, stem-cells mediated gene therapy, genetic vaccination, immunological precursor cell-mediated gene therapy and vectors. METHODS:We searched the current literature through searchable online databases, journals and other library sources using relevant keywords and search parameters. Only relevant publications in English, between the years 2000 and 2018, with evidences and proper citations, were considered. The publications were then analyzed and segregated into several subtopics based on common words and content. A total of 126 studies were found suitable for this review. FINDINGS:Generally, the pros and cons of each of the gene-based therapies have been discussed based on the results collected from the literature. However, there are certain interventions that require further detailed studies to ensure their effectiveness. We have also highlighted the future direction and perspectives in gene therapy, which, researchers could benefit from.
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, p. 7695364.View/Download from: UTS OPUS or Publisher's site
Tuberculosis (TB), caused by the bacterium Mycobacterium tuberculosis, is the leading cause of mortality worldwide due to a single infectious agent. The pathogen spreads primarily via aerosols and especially infects the alveolar macrophages in the lungs. The lung has evolved various biological mechanisms, including oxidative stress (OS) responses, to counteract TB infection. M. tuberculosis infection triggers the generation of reactive oxygen species by host phagocytic cells (primarily macrophages). The development of resistance to commonly prescribed antibiotics poses a challenge to treat TB; this commonly manifests as multidrug resistant tuberculosis (MDR-TB). OS and antioxidant defense mechanisms play key roles during TB infection and treatment. For instance, several established first-/second-line antitubercle antibiotics are administered in an inactive form and subsequently transformed into their active form by components of the OS responses of both host (nitric oxide, S-oxidation) and pathogen (catalase/peroxidase enzyme, EthA). Additionally, M. tuberculosis has developed mechanisms to survive high OS burden in the host, including the increased bacterial NADH/NAD+ ratio and enhanced intracellular survival (Eis) protein, peroxiredoxin, superoxide dismutases, and catalases. Here, we review the interplay between lung OS and its effects on both activation of antitubercle antibiotics and the strategies employed by M. tuberculosis that are essential for survival of both drug-susceptible and drug-resistant bacterial subtypes. We then outline potential new therapies that are based on combining standard antitubercular antibiotics with adjuvant agents that could limit the ability of M. tuberculosis to counter the host's OS response.
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 2018, '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: UTS OPUS or 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.
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. 230-231.View/Download from: Publisher's site
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: UTS OPUS or 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.
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: UTS OPUS or 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
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: UTS OPUS or 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. miR503, 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 miR503 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 miR503 in different cancers and elaborate on its mechanism of action.
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
In the United States, the estimated number of new cancer cases in 2018 will be approx. 1.7 million. Historically, combination chemotherapy has been the primary choice of treatment. However, chemotherapeutics have pharmaceutical limitations, among which include problems with stability and aqueous solubility. Likewise, dose limiting toxicity is significant with nonspecific toxicity to healthy cells, hair loss, loss of appetite, peripheral neuropathy and diarrhea being typical side effects. The emergence of Multidrug resistance (MDR) also presents s a significant challenge for the successful treatment of cancer whereby cancer cells become cross resistant to many of the chemotherapeutic agents used. Nanotechnology presents a new frontier for cancer treatment. It holds potential in minimizing systemic toxicity through the development of functionalized particles for targeted treatment. They also provide an alternative strategy to circumvent multidrug resistance as they have a capacity to by-pass the drug efflux mechanism associated with this phenotype. Aside from the advantages they offer in treatment, nanoparticles are also emerging to be valuable diagnostic entities. This article highlights the various ways nanotechnology is being used to improve the treatment and management of cancer. We also discuss the opportunities and obstacles in this area and provide an up to date review of progress in the treatment of cancer.
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.
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: UTS OPUS or 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.
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: UTS OPUS or Publisher's site
Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1 (IL-1) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3±3.06nm and -61.0mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1g/mL, 5g/mL) resulted in significant (p<0.05) reduction in...
Gupta, G, Bebawy, M, Pinto, TDJA, 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
Cancer is a complicated transformational progression that fiercely changes the appearance of cell physiology as well as cells' relations with adjacent tissues. Developing an oncogenic characteristic requires a wide range of modifications in a gene expression at a cellular level. This can be achieved by activation or suppression of the gene regulation pathway in a cell. Tristetraprolin (TTP or ZFP36) associated with the initiation and development of tumors are regulated at the level of mRNA decay, frequently through the activity of AU-rich mRNA-destabilizing elements (AREs) located in their 3'-untranslated regions. TTP is an attractive target for therapeutic use and diagnostic tools due to its characteristic appearance in cancer tissue alone. Thus, the illumination of TTP in diverse types of cancer might deliver additional effective remedies in the coming era for cancer patients. The objective of this review is to familiarize the reader with the TTP proteins, focus on efficient properties that endow them with their effective oncogenic potential, describe their physiological role in cancer cells, and review the unique properties of TT, and of TTP-driven cancer.
Dua, K, Gupta, G, Koteswara Rao, N & Bebawy, M 2018, 'Nano-antibiotics: a novel approach in treating P. aeruginosa biofilm infections.', Minerva medica, vol. 109, no. 5, p. 400.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
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 (AlCl3)-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 (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action. Methods: Memory deficiency was produced by AlCl3 (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: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 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 AlCl3-induced learning and memory shortages along with diminution of AlCl3-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.
Bintiazeran, NS, Diyanabintizazali, N, Sedatimur, S, Özdoan, AL, Ekizolu, M, Sheshala, R, Dua, K, Sahu, PS & Şenel, S 2017, 'Moxifloxacin loaded chitosan gel formulations for the treatment of periodontal diseases', Journal of Polymer Materials, vol. 34, no. 1, pp. 157-169.View/Download from: UTS OPUS
For treatment of periodontal diseases, the local delivery of antimicrobials into periodontal pocket has been shown to be more effective than the systemic delivery. However, the major challenge for the formulators is the removal of the delivery system from the application side due to the salivation as well as the movement of the tongue. Mucoadhesive polymers have been successfully utilized to go over this obstacle. In recent years, particularly chitosan has been widely investigated for periodontal delivery systems not only for its mucoadhesive properties but also for its antimicrobial activity. In our study, we developed a local delivery system for an antimicrobial drug, moxifloxacin hydrochloride (MF), at 0.5% w/v, using chitosan for the treatment of periodontal diseases. For comparison, formulations based on two other mucoadhesive polymers, carbomer (Carbopol 940®) and hydroxypropyl methylcellulose(HPMC) were also prepared. Viscosity, mucoadhesion, drug release and permeation properties as well as the antimicrobial activity of the gel formulations was evaluated in vitro. The developed formulations with a suitable viscosity for application were found to remain on the mucosa and release the drug in a prolonged fashion. Drug release from the formulations was found to be dependent on the viscosity of the formulations. A relative correlation was found between viscosity and mucoadhesion for the polymers investigated, with an order of HPMC>Carbopol®=Chitosan. Permeation of the drug was increased in presence of chitosan. The antimicrobial activity of MF against Staphylococcus aureus and Streptococcus mutans were found to be enhanced with the developed formulations. The highest antimicrobial activity was observed with the chitosan-based formulations, due to the synergic effect of chitosan itself. Our results showed that chitosan based formulation is a promising local delivery system for treatment of periodontal disease by increasing the effect of the drug due to its muco...
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: UTS OPUS or 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±1.43m. 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.
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: UTS OPUS or 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 & M, H 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: UTS OPUS or Publisher's site
Urolithiasis is a painful disorder in which stones are formed in the kidney, bladder or urethra. There are no proper therapeutic treatments available for kidney stones and people suffering from larger stones have to undergo surgery which has many side effects. A natural remedy with therapeutic effects that can dissipate and remove even the larger stones would eliminate the need of a surgery and the risks associated with it. The flowers of Phlogacanthus thyrsiformis used in culinary recipes in the north eastern India are also widely used as a folklore medicine for the treatment of kidney stones and liver disorders. The aim of this study was to evaluate the prophylactic and therapeutic activity of the aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles against struvite urinary stones and calcium oxalate kidney stones. A kidney stone inhibition study was carried out on struvite stones grown in gel medium and calcium oxalate stones in rat models using an aqueous extract of P. thyrsiformis flowers and its biofabricated silver nanoparticles. The aqueous extract of P. thyrsiformis flowers and their biofabricated silver nanoparticles, obtained by a green synthetic method, were used to treat struvite urinary stones in vitro and calcium oxalate kidney stones in vivo. Struvite stones were grown in tubes by gel diffusion technique and were treated with varying concentrations of the extract and its nanoparticles. The size of the struvite stones was monitored for 96h using a travelling microscope. Calcium oxalate stones were induced in male Wistar rats by feeding ethylene glycol-ammonium chloride mixture for 14days. Both, prophylactic and therapeutic activities were evaluated by analyzing the urine, serum and histopathological parameters of the rats. The qualitative screening of water extract unveiled the presence of flavonoids as a major constituent. Both, the extract and the nanoparticles effectively reduced the size of struvite stones in vi...
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: UTS OPUS or 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, Narayan Sharma, G, Kumar Singh, S, Mishra, A, Kumar Sharma, R & 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: UTS OPUS or Publisher's site
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: UTS OPUS or 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: UTS OPUS or 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: UTS OPUS or 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 & formulation, vol. 11, no. 1, pp. 36-41.View/Download from: Publisher's site
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.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.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.All these observations imply that Hemidesmusindicus extract possesses anti-psychotic activity in experimental animals.
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: UTS OPUS or 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, de Souza Braga, M, Kikuchi, IS, de Jesus Andreoli Pinto, T & 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: UTS OPUS or Publisher's site
The present study aimed to develop matrix-type transdermal drug delivery system (TDDS) of metoprolol tartrate using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA). The transdermal films were evaluated for physical parameters, Fourier transform infrared spectroscopy analysis (FTIR), differential scanning calorimetry (DSC), in vitro drug release, in vitro skin permeability, skin irritation test and stability studies. The films were found to be tough, non-sticky, easily moldable and possess good tensile strength. As the concentration of PVA was increased, the tensile strength of the films was also increased. Results of FTIR spectroscopy and DSC revealed the absence of any drug-polymer interactions. In vitro release of metoprolol followed zero-order kinetics and the mechanism of release was found to be diffusion rate controlled. In vitro release studies of metoprolol using Keshary-Chein (vertical diffusion cell) indicated 65.5 % drug was released in 24 h. In vitro skin permeation of metoprolol transdermal films showed 58.13 % of the drug was released after 24 h. In vitro skin permeation of metoprolol followed zero-order kinetics in selected formulations. The mechanism of release was found to be diffusion rate controlled. In a 22-day skin irritation test, tested formulation of transdermal films did not exhibit any allergic reactions, inflammation, or contact dermatitis. The transdermal films showed good stability in the 180-day stability study. It can be concluded that the TDDS of MPT can help in bypassing the first-pass effect and will provide patient improved compliance, without sacrificing the therapeutic advantages of the drugs.
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 and PPAR.', Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, vol. 89, pp. 447-453.View/Download from: UTS OPUS or Publisher's site
In India syzygium cumini (Myrtaceae) is commonly used traditional medicine to treat diabetes. The present study was undertaken to assess an investigation of antihyperglycemic and antidyslipidemic properties of aqueous extract of Syzigium Cumini (SC) in diabetic rats fed a high cholesterol diet. The aqueous extract of SC was screened for antihyperglycemic and antidyslipidemic activity by streptozotocin induced diabetes in rats. Animals were treated with 100, 200 and 400mg/kg body weight of aqueous extract of SC. Metformin were used as reference antihyperglycemic drugs for comparison. Administration of aqueous extract of SC or metformin for 21days resulted in a significant (P<0.05) reduction in serum glucose, insulin and Homeostasis model assessment of insulin resistance (HOMA-IR) compared with diabetic controls. Treatment with 100mg/kg/day aqueous extract of SC did not result in a significant reduction in serum insulin levels, but 200mg/kg/day and 400mg/kg/day, aqueous extract of SC and metformin showed significant reductions 17.89%, 19.60% and 24.40%, respectively. Furthermore, administration of 100, 200 and 400mg/kg/day, aqueous extract of SC and metformin resulted in significant decrease in insulin resistance of 19.20%, 41.59%, 51.55% and 68.68%, respectively. In high fat diet- streptozotocin (HFD - STZ) treated rats -cells function (HOMA-B) were markedly reduced (5.8-fold), however observed a significant (P<0.01) improvement of -cell function with aqueous extract of SC (400mg/kg/day) and metformin. The aqueous extract of SC seeds exhibits significant insulin-sensitizing, antidyslipidemic, antioxidant, anti-inflammatory and -cell salvaging activity in HFD-STZ-induced type 2 diabetic rats via overexpression of PPAR and PPAR activity, affirming its potential to be used in the prevention and treatment of type 2 diabetes mellitus (T2DM). Further isolation and characterization of active components in SC seed extract are needed to explore the other possible mech...
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: UTS OPUS or 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- (A) 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-, 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...
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: UTS OPUS or 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: UTS OPUS or 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 g 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, 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: UTS OPUS or Publisher's site
The rapid advancement in the area of microRNAs (miRNAs) from discovery to their translation into therapeutic moieties reflects their significance as important regulators in the management of disease pathology. The miRNAs can potentially be a new class of drugs in the near future for the treatment of various lung diseases, but it lacks the current knowledge how these identified therapeutic moieties can be designed into an effective, patient complaint and targeted drug delivery system. miRNAs have characteristic features like small size and low molecular weight which makes them easily translated into an effective drug delivery system. In this review, we have summarised the concept of miRNAs and different approaches which can be employed to deliver miRNAs effectively and safely to the target cells including the challenges associated with their development in particular emphasis on pulmonary diseases. Such approaches will be of interest for both the biological and formulation scientists to understand and explore the new vistas in the area of miRNA delivery for pulmonary inflammatory diseases.
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: UTS OPUS or 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.
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: UTS OPUS or 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.
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: UTS OPUS or 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-B-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.
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: UTS OPUS or 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.
Dua, K, Shukla, SD, de Jesus Andreoli Pinto, T & Hansbro, PM 2017, 'Nanotechnology: Advancing the translational respiratory research.', Interventional medicine & applied science, vol. 9, no. 1, pp. 39-41.View/Download from: UTS OPUS or Publisher's site
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, 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: UTS OPUS or Publisher's site
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.
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.
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.
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 m. 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.
Rediguieri, CF, Sassonia, RC, Dua, K, Kikuchi, IS & de Jesus Andreoli Pinto, T 2016, 'Impact of sterilization methods on electrospun scaffolds for tissue engineering', European Polymer Journal, vol. 82, pp. 181-195.View/Download from: UTS OPUS or Publisher's site
© 2016 Elsevier Ltd Tissue engineering is a growing area within the regenerative medicine. The electrospun scaffolds are the most promising devices for translating engineered tissues into patients. However, in order to be used in clinical practice, one of the important fundamental aspects of the scaffold is to be sterile keeping the fact of patient safety in mind. Due to the various properties of electrospun fibers, such as high porosity and surface area, the effects of sterilization could have different outcomes than those observed in ordinary medical devices. Therefore, the present article provides an insight into the various sterilization methods that have been applied to electrospun scaffolds and their effects on scaffolds morphology, hydrophilicity, other physico-chemical and mechanical properties and the performance of seeded cells after sterilization. In conclusion, the information provided in the review will help all scientists involved in this interdisciplinary field to understand and apply the knowledge in selection of appropriate sterilization method for the electrospun scaffolds.
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 & formulation, vol. 10, no. 1, pp. 72-76.View/Download from: Publisher's site
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 against paracetamol-induced liver toxici...
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.
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
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.The aim of the present investigation was to develop bilayered tablets of two incompatible drugs; telmisartan and simvastatin.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.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).Stable and compatible bilayer tablets containing telmisartan and simvastatin were developed with better patient compliance as an alternative to existing conventional dosage forms.
Ghisleni, DDM, Braga, MDS, Kikuchi, IS, Braşoveanu, M, Nemţanu, MR, Dua, K & Pinto, TDJA 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: UTS OPUS or Publisher's site
The present review article provides an overview of the published literature concerning microbial quality of medicinal plants and products and their decontamination methods. It is important to analyze different aspects regarding the cultivation, growing, harvesting, storage, manufacturing, and decontamination of medicinal plant products. Herbal medicinal plants bear a massive microbial load leading to contamination and mycotoxin, which needs to be considered, and properly controlled using suitable sterilization and decontamination methods.The main focus of this review is on the definition, advantages, disadvantages and applications of decontamination methods, particularly to show that one must consider the characteristics of the initial sample to be decontaminated.The effects of various methods (ozone, plasma, irradiation) on medicinal herbs and products treated for microbiological decontamination are dependent on factors related to microbial load (i.e., nature and amount of initial contamination), herb/product matrix (i.e., complexity of chemical composition, physical state - solid or liquid) and treatment conditions (i.e., time, irradiation dose, absence or presence of oxygen). In addition, it is important to accept some loss of the chemical compounds, while decreasing microbial load to acceptable limits according to official herbal pharmacopoeias and literature, thus ensuring a final product with quality, safety and therapeutic efficacy.The conclusion, which comes from this contribution, is that herbal medicine has more contaminants than a chemically welldefined drug, thus, good manufacturing practices should be followed.
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: UTS OPUS or Publisher's site
Proniosomes are the new generation provesicular drug delivery system of non-ionic surfactant, lecithin and cholesterol which upon reconstitution get converted into niosomes. The objective of current study was to develop stable and sustain transdermal delivery system for lornoxicam. Lornoxicam-loaded topically applied proniosomal gel was formulated, optimized, and evaluated with the aim to deliver drug transdermally. Lornoxicam-loaded proniosomal gels were prepared that contained Lutrol F68 and lecithin as surfactants, cholesterol as a stabilizer, and minimal amount of ethanol and trace water. The resultant lornoxicam-loaded proniosomal gel were assessed for stability and the proniosomes-derived niosomes were characterized for morphology, size, zeta potential, and entrapment efficiency, which revealed that they were suitable for skin application. The coacervation phase separation technique was used in formulation of lornoxicam proniosomal gel and the gel was further assessed for in vitro permeation of lornoxicam through the freshly excised rat skin and the cumulative permeation amount of lornoxicam from proniosome, all exhibited significant increase as compared to 1.0 % lornoxicam-loaded pure gel. The optimized F5 batch had shown maximum entrapment efficiency up to 66.98 %. It has shown sustained drug release for more than 24 h. The skin permeability of proniosomal gel was found to be 59.73 %. The SEM and zeta potential studies showed formation of good and stable vesicles. Thus, proniosomes proved to have better potential for transdermal delivery of lornoxicam over conventional gel formulations.
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: UTS OPUS or Publisher's site
The present study aimed to improve solubility and prolong the release duration of a poorly soluble drug using a combination of two different types of formulations (solid dispersion and microspheres). The solid dispersions were prepared by fusion method using urea and mannitol as hydrophilic carriers. Microspheres were prepared by solvent evaporation method using Eudragit L-100 (EL100) and Eudragit RS PO (ERS) as rate-controlling polymers. Flurbiprofen (FBP)-urea (1:2) solid dispersion and microspheres of FBP-EL-100-ERS (1:0.25:0.75) were used for the development of controlled release formulation by mixing them in different proportions. The FBP-containing formulations were evaluated for percentage yield, drug content, morphology, in vitro release, and in vivo anti-inflammatory activity. The best selected formulation was further evaluated for the controlled and improved effects. SEM photomicrograph confirmed the spherical shape of microspheres and with particle size in the range of 73.5-85.4 m. In vitro release of FBP from controlled release formulations indicated that the formulation containing solid dispersion:microspheres (1:0.5) yielded prolonged effect up to 10 h. The release kinetics followed zero-order, and the mechanism of drug release was found to be diffusion rate controlled. This formulation had shown better inhibition of edema of rat paw up to 16 h and identified as a suitable product for controlled delivery of FBP. In conclusion, the concept of using a binary mixture of solid dispersion and microspheres can be used for other drugs that exhibit a poor solubility in stomach pH and a faster release in intestinal pH.
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 & formulation, vol. 10, no. 2, pp. 165-173.View/Download from: Publisher's site
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.The research article also reviewed details of various existing patents associated with comprehensive compilation regarding the therapeutic application of berberine and related forms.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.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 5.-iodothyronine deiodinase (5.DI) enzyme by NF-kB pathway.From the findings of the current study it can be concluded that berberine chloride possesses both thyroid stim...
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 & formulation, vol. 9, no. 2, pp. 167-182.View/Download from: Publisher's site
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.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.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.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, L & Dua, K 2015, 'Preparation and characterization of cefuroxime axetil solid dispersions using hydrophilic carriers', International Journal of Pharmaceutical Investigation, vol. 5, no. 3, pp. 171-171.View/Download from: Publisher's site
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: UTS OPUS or 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, J, Adokar, B & Dua, K 2015, 'Development and evaluation of in situ gel of pregabalin', International Journal of Pharmaceutical Investigation, vol. 5, no. 4, pp. 226-226.View/Download from: Publisher's site
Madan, J, Pawar, K & Dua, K 2015, 'Solubility enhancement studies on lurasidone hydrochloride using mixed hydrotropy', International Journal of Pharmaceutical Investigation, vol. 5, no. 2, pp. 114-114.View/Download from: Publisher's site
Madan, JR, Argade, NS & Dua, K 2015, 'Formulation and evaluation of transdermal patches of donepezil.', Recent patents on drug delivery & formulation, vol. 9, no. 1, pp. 95-103.View/Download from: Publisher's site
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.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.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.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.
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.
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.
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 M/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 mol 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.
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: UTS OPUS or 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 g/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, 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: UTS OPUS or Publisher's site
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: UTS OPUS or 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 g/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, Dua, K & Khude, P 2014, 'Development and evaluation of solid lipid nanoparticles of mometasone furoate for topical delivery', International Journal of Pharmaceutical Investigation, vol. 4, no. 2, pp. 60-60.View/Download from: Publisher's site
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: UTS OPUS or 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.
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, Gupta, G, Kumar, D, Sheshala, R & Chakravarthi, S 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. 183-183.View/Download from: UTS OPUS or Publisher's site
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: UTS OPUS or 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: UTS OPUS or Publisher's site
The present work relates with developing long acting sustain release microspheres of ropinirole hydrochloride (RPN) for treatment of Parkinsons 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: UTS OPUS or 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: UTS OPUS or 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.
Aim: The objective of the present investigation was to study the effect of PVP on in vitro dissolution of aceclofenac from coprecipitates. Materials and Methods: Aceclofenac coprecipitates (CP) with different drug loadings were prepared and in vitro dissolution studies of pure drug, physical mixtures and coprecipitates were carried out. Results: Coprecipitates of aceclofenac with PVP 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. Coprecipitates in 1:2 ratio showed maximum dissolution rate in comparison to other ratios. Amorphous nature of the drug in coprecipitates was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in coprecipitates compared to the pure drug. FT- IR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and PVP in coprecipitates in solid state. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting, eutectic formation and solubilizing effect of the carrier from the coprecipitates of aceclofenac. Conclusion: dissolution of aceclofenac can be enhanced by the use of hydrophilic carriers like PVP.
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: UTS OPUS or Publisher's site
In order to enhance the absorption of dissolution rate of nitrendipine (NIT), solid dispersions were prepared using two water soluble carriers, polyvinylpyrrolidone K30 (PVP K30) and polyethylene glycol 4000 (PEG-4000), by solvent and fusion method. The dissolution profile of solid dispersions were compared to the pure drug in both pH 1.2 hydrochloric acid and pH 6.8 phosphate buffer and the results have shown profound improvement in drug release. The solubility of solid dispersion was increased by several folds when compared to pure NIT. The physicochemical properties of the solid dispersions were examined using analytical techniques. The results of microscopic studies, x-ray powder diffraction (XRPD), and differential scanning calorimetric (DSC) analysis confirmed the amorphous state of solid dispersion in comparison to the crystalline nature of pure drug, proposing that NIT was molecularly dispersed in the polymer matrices, which were accounted for by dissolution rate enhancement. Fourier transform infrared (FTIR) spectroscopic analysis indicated the presence of hydrogen bonding between NIT and the polymers, which also explained the improvement in solubility and dissolution rate. In conclusion, solid dispersion of NIT with PVP K30 and PEG-4000 improved the solubility and rate of dissolution, which may improve the absorption of the drug and subsequently the bioavailability of NIT. © 2012 Copyright Taylor and Francis Group, LLC.
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: UTS OPUS or 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.
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: UTS OPUS or 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, 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: UTS OPUS or Publisher's site
The objective of the present investigation was to study the effect of polyvinylpyrrolidone (PVP) on in vitro dissolution of aceclofenac from solid dispersions. Aceclofenac binary solid dispersions (SD) with different drug loadings were prepared using the melting or fusion method. In vitro dissolution of pure drug, physical mixtures, and solid dispersions were carried out. Solid dispersion of aceclofenac with PVP showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1N HCl, pH 1.2 and phosphate buffer, pH 7.4. Solid dispersions in 1:2 ratio showed maximum dissolution rate in comparison to other ratios. The amorphous nature of the drug in solid dispersion was confirmed by scanning electron microscopy and a decrease in enthalpy of drug melting in solid dispersion compared to the pure drug. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between aceclofenac and PVP in solid dispersions in solid state. Dissolution enhancement was attributed to decreased crystallinity of the drug and to the wetting, eutectic formation, and solubilizing effect of the carrier from the solid dispersions of aceclofenac. In conclusion, dissolution of aceclofenac can be enhanced by the use of hydrophilic carriers like PVP. © Taylor & Francis Group, LLC.
Dua, K, Pabreja, K & Ramana, MV 2011, 'Enhancement of dissolution behavior of aceclofenac by complexation with -cyclodextrin-choline dichloride coprecipitate', Journal of Dispersion Science and Technology, vol. 32, no. 10, pp. 1477-1484.View/Download from: UTS OPUS or Publisher's site
The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in -cyclodextrin (-CD) on in vitro dissolution of aceclofenac (AF) from molecular inclusion complexes. The molecular inclusion complexes of AF with -CD coprecipitated with CDC in 1:1 and 1:2 M ratio were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures, and cyclodextrin inclusion complexes (AF--CD-CDC) were carried out. Molecular inclusion complexes of aceclofenac with coprecipitated -CD showed considerable increase in the dissolution rate in comparison with physical mixture and pure drug in 0.1 N HCl, pH 1.2 and phosphate buffer, pH, 7.4. Inclusion complexes with 1:2 M ratio showed maximum dissolution rate in comparison to other ratios. FTIR spectroscopy and differential scanning calorimetry studies indicated no interaction between AF and -CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of b-CD. The in vitro release from all the formulations was best described by first order kinetics (R2=1/4 0.9354 and 0.9268 in 0.1 N HCl and phosphate buffer, respectively) followed by Higuchi release model (R2=1/4 0.9029 and 0.9578 in 0.1 N HCl and phosphate buffer, respectively). In conclusion, dissolution of aceclofenac can be enhanced by using the -CD-CDC coprecipitate as a host molecule. © Taylor & Francis Group, LLC.
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: UTS OPUS or Publisher's site
The objective of the present investigation was to study the effect of presence of choline dichloride (CDC) in -cyclodextrin (-CD) on in vitro dissolution of Ursodeoxycholic acid (UDCA) from molecular inclusion complexes. The molecular inclusion complexes of UDCA with -CD coprecipitated with CDC were prepared using kneading method. In vitro dissolution of pure drug, physical mixtures and cyclodextrin inclusion complexes (UDCA--CD- CDC) were carried out. Molecular inclusion complexes of Ursodeoxycholic acid with coprecipitated -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 -CD-CDC in complexes in solid state. Dissolution enhancement was attributed to the formation of water soluble inclusion complexes with the precipitated form of -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 -CD-CDC coprecipitate as a host st molecolec.
Dua, K, Pabreja, K, Ramana, MV & Lather, V 2011, 'Dissolution behavior of -cyclodextrin molecular inclusion complexes of aceclofenac', Journal of Pharmacy and Bioallied Sciences, vol. 3, no. 3, pp. 417-425.View/Download from: UTS OPUS or 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: UTS OPUS or 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: UTS OPUS or 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: UTS OPUS or 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-1 and tumor necrosis factor-, 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.
Dua, K, Pabreja, K & Ramana, MV 2010, 'Aceclofenac topical dosage forms: in vitro and in vivo characterization.', Acta pharmaceutica (Zagreb, Croatia), vol. 60, no. 4, pp. 467-478.View/Download from: Publisher's site
Aceclofenac is a new generation non-steroidal anti-inflammatory drug showing effective anti-inflammatory and analgesic properties. It is available in the form of tablets of 100 mg. Importance of aceclofenac as a NSAID has inspired development of topical dosage forms. This mode of administration may help avoid typical side effects associated with oral administration of NSAIDs, which have led to its withdrawal. Furthermore, aceclofenac topical dosage forms can be used as a supplement to oral therapy for better treatment of conditions such as arthritis. Ointments, creams, and gels containing 1% (m/m) aceclofenac have been prepared. They were tested for physical appearance, pH, spreadability, extrudability, drug content uniformity, in vitro diffusion and in vitro permeation. Gels prepared using Carbopol 940 (AF2, AF3) and macrogol bases (AF7) were selected after the analysis of the results. They were evaluated for acute skin irritancy, anti-inflammatory and analgesic effects using the carrageenan-induced thermal hyperalgesia and paw edema method. AF2 was shown to be significantly (p < 0.05) more effective in inhibiting hyperalgesia associated with inflammation, compared to AF3 and AF7. Hence, AF2 may be suggested as an alternative to oral preparations.
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 degrees 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.
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.
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.
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. 328-331.View/Download from: Publisher's site
The naturally occurring xanthone glycoside mangiferin has been isolated by column chromatography from the ethanol extract of stem bark of Mangifera indica. Mangiferin was further converted to 5-(N-phenylaminomethyleno)mangiferin, 5-(N-p-chlorophenylaminomethyleno) mangiferin, 5-(N-2-methylphenylaminomethyleno) mangiferin, 5-(N-p-methoxyphenylaminomethyleno) mangiferin, 5-(N, N-diphenylaminomethyleno) mangiferin, 5-(N--napthylaminomethyleno) mangiferin and 5-(N-4-methylphenylaminomethyleno) mangiferin. Mangiferin and its analogues were characterized by melting point and R(f) value determination and through spectral technique like UV, IR, and NMR spectral analysis. The synthesized compounds were screened for antimicrobial activity.
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
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 m. 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.
Dua, K, Ramana, MV, Sara, UVS, Himaja, M, Agrawal, A, Garg, V & Pabreja, K 2007, 'Investigation of enhancement of solubility of norfloxacin beta-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 beta-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 beta-cyclodextrin complexes reduces the pH of the immediate microenvironment of the drug below pH 4. In the present work, beta-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 beta-cyclodextrin. Disc diffusion studies have shown larger diameters of zone of inhibition indicating a greater diffusivity of the drug into the agar medium.
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.
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.View/Download from: UTS OPUS
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.
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.
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.