Dr. Varsha Pokharkar - Academia.edu (original) (raw)

Papers by Dr. Varsha Pokharkar

Molecules

Currently, particular interest among the scientific community is focused on exploring the use of ... more Currently, particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30–100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility wit...

Letters in Drug Design & Discovery

Background: Alzheimer's disease (AD) is major cause of morbidity in world, affecting about 5.... more Background: Alzheimer's disease (AD) is major cause of morbidity in world, affecting about 5.8 million and 4 million people in India. Current anti-AD treatments are limited in their usage. Objective: Some natural promising herbal drugs that might be utilised as an alternative treatment for AD have been reported by several researchers for their neuroprotective action. Based on this, we chose these flavonoids Curcumin, Quercetin, Bilobalide, Ferulic acid, Reservetrol and donepezil (conventional Acetylcholine esterase inhibitor) as ligands for molecular docking studies. Methods: The Molecular docking interactions studied between these components with Acetylcholine esterase, Butyrylcholine esterase, and tau protein by Auto dock software. Prediction of ADME properties were performed by Swiss ADME. Binding interactions of the ligands at target protein binding sites were examined using Discovery studio visualizer 2021. Results: The binding energy for quercetin in the active site of enz...

Brazilian Journal of Pharmaceutical Sciences

Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pec... more Diltiazem hydrochloride (DLH) is a calcium channel blocker useful for the treatment of angina pectoris, arrhythmia, and hypertension. DLH having a short half-life needs frequent administration for successful treatment but this poses a problem of poor patient compliance. These requirements are served by elementary osmotic pump tablets (EOP) based controlledrelease (CR) systems. Quality by design (QbD) approach assists in screening various factors with subsequent assessment of critical parameters that can have a major impact on the scalability of EOP. Tablets were formulated using wet granulation method followed by osmotic coating. Factorial design based QbD strategy aided in defining the risk assessment of influential variables such as hydrophilic polymers and osmotic coat component on the in-vitro release kinetics of the designed EOP tablets. These formulated EOP systems followed zero-order kinetics, a characteristic feature of EOPs. EOP tablets were formulated applying a systematic QbD statistical approach. The formulated DLH EOP systems with improved concentrationindependent behavior helped to address the challenges of IR formulation. Application of QbD strategy in ascertaining the scalability of DLH EOP formulation would help pharmaceutical industries in the translation of EOP based drug delivery systems from R&D to market.

Research Journal of Pharmacy and Technology, 2010

Of the various attempts to prolong the gastric residence time, use of mucoadhesive polymers is th... more Of the various attempts to prolong the gastric residence time, use of mucoadhesive polymers is the most sought after. The main objective was to prolong the residence of metformin hydrochloride formulation in upper gastrointestinal tract. Herein we report a method for the preparation of mucoadhesive drug delivery system for metformin hydrochloride, a water soluble drug, using HPMC K4M, Carbopol 934P and Carbopol 971P as mucoadhesive and release controlling polymers. The selection of mucoadhesive polymer was done on the basis of water uptake, shear stress measurement and detachment force. The formulations were prepared by tablet compression method and were evaluated for water uptake, mucoadhesion, differential scanning calorimetry, in vitro and in vivo release. The water sorption studies of the formulation indicated a curvilinear relation for the drug: polymer ratio. The in vitro release studies revealed that the optimum combination of HPMC K4M and Carbopol 971P in the formulation lea...

Objective: The present study was designed with an objective of developing a validated, simple, ac... more Objective: The present study was designed with an objective of developing a validated, simple, accurate and precise HPTLC method for the determination of aqueous extract of Bacopa monnieria. Methods: High performance thin layer chromatography (HPTLC) method was developed and validated for rapid analysis of aqueous extract of dried Bacopa monnieria powder. Chromatographic separation was achieved on precoated silica gel HPTLC aluminum plate 60 F254 using dichloromethane: methanol (2:4.5 v/v) as mobile phase. Detection was performed at 294 nm wavelength densitometrically. Results: The limit of detection and quantitation were 300 ng/spot and 1000 ng/spot, respectively. The linear regression analysis data for calibration plots showed good linear relationship (R2 = 0.999) in the concentration range of 2000-12000 ng/spot. Accuracy (99.34 to 100.59%) and precision (% RSD ˂ 2%) of the developed HPTLC method was in accordance with the ICH guidelines. Conclusion: The developed procedure can be...

JPC – Journal of Planar Chromatography – Modern TLC, 2020

The purpose of the present study was to develop a simple, rapid and sensitive high-performance th... more The purpose of the present study was to develop a simple, rapid and sensitive high-performance thin-layer chromatography (HPTLC) method for the simultaneous estimation of 5-fluorouracil (5FU) and berberine (BER) in rabbit plasma. BER and 5-FU are currently under extensive studies for their synergistic effects in cancer chemotherapy. The HPTLC method was developed using TLC aluminum plates precoated with silica gel 60 F 254 as the stationary phase. A mixture of toluene:methanol:ethyl acetate:formic acid (6:2:6:1, v/v) was used as the solvent system for development and detection was carried out at 266 nm. The method was designed to obtain the most optimum retardation factors (Rf) with best resolution. The Rf values of BER and 5-FU were 0.28 ± 0.02 and 0.57 ± 0.02, respectively. The plasma extraction was optimized using ethyl acetate. The method was validated in compliance with the USFDA guideline for bioanalytical method validation. The method was found to be linear in the range of 20 ng/spot to 300 ng/spot with R 2 of 0.9964 for 5-FU and 0.9943 for BER. The lower limit for quantification (LLOQ) of BER and 5-FU in rabbit plasma were obtained as 29 ng/spot and 26 ng/spot, respectively. The stability of BER and 5-FU in plasma were confirmed during freeze-thaw cycles (−20°C), on bench for 5 h and long term for 21 days. The proposed method was validated statistically and was precise, accurate and sensitive for the estimation of BER and 5-FU in rabbit plasma. This method can be extended for therapeutic drug monitoring and pharmacokinetic studies in rabbits.

Drug Delivery and Translational Research

Frontiers in Pharmacology, 2021

Drug-resistant species of tuberculosis (TB), which spread faster than traditiona TB, is a severel... more Drug-resistant species of tuberculosis (TB), which spread faster than traditiona TB, is a severely infectious disease. The conventional drug therapy used in the management of tuberculosis has several challenges linked with adverse effects. Hence, nanotherapeutics served as an emerging technique to overcome problems associated with current treatment. Nanotherapeutics helps to overcome toxicity and poor solubility issues of several drugs used in the management of tuberculosis. Due to their diameter and surface chemistry, nanocarriers encapsulated with antimicrobial drugs are readily taken up by macrophages. Macrophages play a crucial role as they serve as target sites for active and passive targeting for nanocarriers. The surface of the nanocarriers is coated with ligand-specific receptors, which further enhances drug concentration locally and indicates the therapeutic potential of nanocarriers. This review highlights tuberculosis’s current facts, figures, challenges associated with c...

In the current study, human keratinocyte cell line was used as in vitro cell culture model to elu... more In the current study, human keratinocyte cell line was used as in vitro cell culture model to elucidate the effects of the fatty acid chain length of acylglutamate (amino acid-based surfactant) namely, sodium cocoyl glutamate, sodium lauroyl glutamate, and sodium myristoyl glutamate on their cytotoxicity and the ultraviolet B induced phototoxicity. The endpoint used to assess toxicity was a tetrazolium-based assay whereas, the phototoxic potential of acylglutamate surfactants was predicted using two models namely, the Photo-Irritation Factor and Mean Photo Effect. The results of this study showed that the fatty acid chain length of acylglutamate greatly influences toxic effects on human keratinocyte cells. In addition, all the acylglutamate surfactants tested on human keratinocyte cells demonstrated significantly less cytotoxicity (when irradiated and non-irradiated with ultraviolet B light; p < 0.05) and no phototoxic potential was observed in any of the acylglutamate surfactants, when compared with the positive control chlorpromazine. In conclusion, the in vitro studies confirm the suitability of sodium lauroyl glutamate destined for the synthesis and stabilization of lipid nanoparticles.

Polymeric Nanoparticles as a Promising Tool for Anti-cancer Therapeutics, 2019

Polymers have evolved as an intrinsic part of conventional and advanced drug delivery systems, es... more Polymers have evolved as an intrinsic part of conventional and advanced drug delivery systems, especially nanoparticulate drug delivery systems. Natural polymers are favored over synthetic polymers in pharmaceutical and drug delivery applications owing to their benevolent properties such as their biodegradable, biocompatible, widely available, renewable, economical, sustainable, and nontoxic nature. These biopolymers are explored in nanoparticulate drug delivery applications to justify multifarious functions. Extensive research efforts have been focused toward exploring various natural resources like plants, algae, fungi, yeast, bacteria, and their products in developing biopolymers for nanoparticle synthesis, surface decoration, and tagging for targeted drug delivery, specifically in cancer therapeutics. Certain microorganisms or their structural parts aid in the fabrication of nanocarriers for delivery of anticancer molecules, directly. This chapter will give an overview of contem...

International Journal of Pharmaceutics, 2020

Polyurethanes (PUs) constitute an essential class of stimuli-responsive and biodegradable materia... more Polyurethanes (PUs) constitute an essential class of stimuli-responsive and biodegradable material, which has significantly contributed to the advancement of polymers utilization in the biomedical field. The bio-erodible PUs construct an active corridor for facilitating drug into tumor cells, which has significantly impacted the progression of nano-micellar delivery systems. The self-assembledcolloidal PUs pose distinctive features such as enhancing the solubility of hydrophobic chemotherapeutics, rapid cellular uptake, triggered erosion and drug release, bio-stimulus sensitivity, improvement in the targeting and proficiency ofbioactive. Cationic PUs can easily be condensed with genetic material to form polyplexes and have shown excellent transfection efficiency for potential gene therapy against various cancers. Their modifiable chemistry offers a tool to impart the desired multifunctionality such as biocompatibility, sensitivity to pH, redox, temperature, enzyme, etc. and ligand conjugation for active targeting. These diverse exceptional properties make them excellent nano-carrier for a variety of bioactive, including chemotherapeutic drugs, DNA, RNA, and diagnostic moieties to the target tissue or cells. The PUs based nano-devices have certainly uncovered the path to achieve ideal systems for controlled personalized therapy. The literature discussed in this review shed light on the research innovations carried out in the last ten years for the development of multifunctional PUs for triggered delivery of bioactive to treat various cancers.

Journal of Pharmaceutics & Drug Delivery Research, 2016

In-Silico Comparative Molecular Docking Studies of Mannan and Mannan Sulphate with Mannose Recept... more In-Silico Comparative Molecular Docking Studies of Mannan and Mannan Sulphate with Mannose Receptor Abstract The design of nanoparticles for macrophages targeted delivery is based upon selection of most specific carbohydrate polymers. The expression of mannose receptor contributes the selective delivery of nanoparticles to macrophages with high specificity and selectivity. The mannose receptor plays a pivotal role through strong binding of sulphated polysaccharides with cysteine-rich (Cys-Rich) domain. In an effort to search novel carbohydrate polymer for macrophage targeted drug delivery this study aims to evaluate the interaction of mannan sulphate with mannose receptor by computational molecular docking studies. Comparative docking studies were performed for mannan and mannan sulphate, isolated commercially from the cell wall of baker’s yeast (Saccharomyces cerevisiae) with 1DQO mannose protein by Auto Dock software. Molecular docking studies of mannan sulphate with 1DQO mannose protein exhibited strong binding interactions. The results indicated that the docking score of mannan and mannan sulphate with 1DQO protein were found to be -4.114 and -7.185 respectively. This molecular docking analysis could contribute to the further development of nanoparticles synthesis, which may aid in targeting drugs to specific parts of human body containing macrophages. This study concludes that mannan sulphate with interesting biological and structural properties may serve as valuable lead for nanoparticles synthesis for the treatment of human ailments in close proximity to future.

Journal of Drug Delivery Science and Technology, 2022

Indian drugs, 2003

Chitosan microspheres containing Naproxen were prepared by glutaraldehyde crosslinking of an aque... more Chitosan microspheres containing Naproxen were prepared by glutaraldehyde crosslinking of an aqueous acetic acid dispersion of chitosan in paraffin oil using dioctyl sulphosuccinate as the stabilising agent. A 3 2 factorial design was used to elucidate the effect of variables viz. the amount of drug and the amount of polymer. Discrete spherical microspheres in the range of 300-900 μm were produced with the encapsulation efficiency of about 85%. Response surfaces were plotted to elucidate the effect of variables on the mean particle size and drug release. The amount of polymer affected the particle size and drug release. The amount of drug exhibited curvilinear relationship for the release. IR spectra revealed no drug-polymer interaction, whereas DSC thermogram was indicative of interaction.

Hindustan antibiotics bulletin, 2007

Carvedilol a poorly water soluble drug undergoes extensive first pass metabolism, which reduces i... more Carvedilol a poorly water soluble drug undergoes extensive first pass metabolism, which reduces its bioavailability to 25-30%. Mouth dissolving tablets of Carvedilol were prepared with the purpose of delivering the drug directly into the systemic circulation and bypassing the hepatic first pass metabolism with a concomitant increase in bioavailability. The solubility of Carvedilol was improved by forming inclusion complex with cyclodextrin which was then further used for the formulation of mouth dissolving tablet. Differential scanning calorimetry and Infrared spectroscopy results indicated no incompatibilities between drug-excipient mixtures. Effect of three different superdisintegrants on disintegration was studied. The formulations were evaluated for drug content, content uniformity, friability, disintegration time and in-vitro dissolution. Tablets containing Carvedilol-beta-cyclodextrin complex exhibited good tablet properties, with 90% drug dissolved within 5 min. This demonstr...

PDA journal of pharmaceutical science and technology, 2010

To overcome many challenges associated with antiretroviral drug therapy, novel drug delivery syst... more To overcome many challenges associated with antiretroviral drug therapy, novel drug delivery systems present an opportunity for formulation scientists to improve the management of patients with HIV/AIDS. The purpose of this study was to prepare a transdermal delivery system for zidovudine using different penetration enhancers incorporated in carbopol 971P gel and to evaluate the same for rheology, percent drug content, drug deposition, in vitro, ex vivo, and in vivo permeation across rat skin. The rheology studies indicated that 1% w/w carbopol gel had a higher linear viscoelastic region, good creep recovery, and desirable viscosity. Among all gel formulations, gel containing cineole and menthol as penetration enhancers attained a steady-state flux of 5.9 mg/cm(2)/h and 5.4 mg/cm(2)/h of zidovudine, respectively, leading to plasma concentration in the therapeutic range. The drug deposition was also found to be highest in the case of gel containing cineole and menthol as penetration ...

Current Drug Delivery

Background: Oseltamivir Phosphate (OP) is an ethyl ester prodrug prescribed for the treatment of ... more Background: Oseltamivir Phosphate (OP) is an ethyl ester prodrug prescribed for the treatment of influenza virus infection. Current marketed formulations of OP have been observed to be supplemented with an adverse effect during post-marketing surveillance. These prerequisites are sufficed by developing a sustained release Dry Powder for Inhalation (DPI). Objectives: The objective of the present study was to develop OP-DPI by an innovative formulation approach comprising of Immediate (IR) and Sustained (SR) Release portions. Methods: DPI formulation comprising IR and SR portions were prepared by spray drying technique using Hydroxy Propyl Methyl Cellulose (HPMC) as the rate-controlling polymer for SR portion. The spray-dried product was further characterized for various pharmaco-technical, in-vitro and in-vivo parameters. Results: OP-DPI showed a burst release of 49% within 15 min further sustaining the drug release up to 9 hrs. The in-vitro aerodynamic performance of OP-DPI showed m...

Pharmaceutics

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment ... more Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it ...