Publications by authors named "Vandana B Patravale"

50 Publications

Docetaxel Loaded Pomegranate Seed Oil Based Nanostructured Lipid Carriers: A Potential Alternative to Current Formulation.

AAPS PharmSciTech 2020 Oct 25;21(8):295. Epub 2020 Oct 25.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga, Mumbai, Maharashtra, 400 019, India.

The current work is focused on the development of docetaxel loaded pomegranate seed oil based lipid nanosystem. Docetaxel loaded pomegranate seed oil nanostructured lipid carriers (DTX-PSO-NLCs) were formulated by the melt emulsification method for parenteral delivery. The developed formulation was characterized in terms of their physicochemical parameters, solid-state characterization, in vitro drug release, in vitro cytotoxicity studies, and in vivo pharmacokinetics and biodistribution studies. Stability studies were carried out as per ICH guidelines Q1A. Melt emulsification method resulted in the formulation of stable DTX-PSO-NLCs with a particle size in the range of 150-180 nm and an entrapment efficiency of 63-65%. The in vitro release showed a slow and sustained release of the drug from the formulation compared to the marketed formulation (i.e., Daxotel®). The formulation was found to be stable for a period of 12 months at conditions of 4°C ± 2°C, 25°C ± 2°C/60% RH ± 5%RH, and 40°C ± 2°C/75% RH ± 5%RH. The developed nanosystem exhibited promising antitumor activity against various types of cancerous cell lines (i.e., MCF7, DU145, U87MG, and NCI-H460) relative to the marketed formulation. The pharmacokinetic evaluation revealed that DTX-PSO-NLCs had a better kinetic profile compared to the marketed formulation. Graphical abstract.
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http://dx.doi.org/10.1208/s12249-020-01839-1DOI Listing
October 2020

Gene Therapy for Prostate Cancer: A Review.

Endocr Metab Immune Disord Drug Targets 2020 May 31. Epub 2020 May 31.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N. P. Marg, Matunga - 400 019, Mumbai, Maharashtra. India.

Background: According to the American Cancer Society, prostate cancer ranks second in terms of mortality and is a front-runner of newly detected cases. Conventional therapies neither eradicated cancer nor increased the life expectancy of patients obviating the need for less toxic as well as efficient therapies to treat cancer. Gene therapy alone or in combination with conventional therapies possesses a strong potential to combat cancer.

Method: This review encompasses a brief note on the etiology and conventional therapy of prostate cancer with an emphasis on gene therapy and its suitability for the treatment of prostate cancer.

Results: A comprehensive range of gene therapy approaches have been successfully explored for prostate cancer treatment in animal models and this has been well translated into early clinical trials. We have also discussed in brief about specific therapeutic genes and suitable vector systems for gene therapy in prostate cancer.

Conclusions: Based on the results of these clinical trials, the application of gene therapy in prostate cancer therapeutics can be satisfactorily established.
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http://dx.doi.org/10.2174/1871530320666200531141455DOI Listing
May 2020

Nose-to-brain delivery: exploring newer domains for glioblastoma multiforme management.

Drug Deliv Transl Res 2020 08;10(4):1044-1056

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai, 400019, India.

Glioblastoma multiforme (GBM) is the most common and aggressive form of the primary brain tumors in humans. The intricate pathophysiology, the development of resistance by tumor cells, and the inability of the drugs to effectively cross the blood-brain and blood-tumor barriers result in poor prognosis for GBM patients, with a median survival time of only 1 to 2 years. Nose-to-brain delivery offers an attractive, noninvasive strategy to enhance drug penetration or transport novel drug/gene carriers into the brain. Although the exact mechanism of intranasal delivery remains elusive, the olfactory and trigeminal nerve pathways have been found to play a vital role in circumventing the traditional barriers of brain targeting. This review discusses the intranasal pathway as a novel domain for delivering drugs and nanocarriers encapsulating drugs/genes, as well as stem cell carriers specifically to the glioma cells. Considering the fact that most of these studies are still in preclinical stage, translating such intranasal delivery strategies from bench to bedside would be a critical step for better management and prognosis of GBM. Graphical abstract.
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http://dx.doi.org/10.1007/s13346-020-00747-yDOI Listing
August 2020

Starch microsponges for enhanced retention and efficacy of topical sunscreen.

Mater Sci Eng C Mater Biol Appl 2019 Nov 12;104:109882. Epub 2019 Jun 12.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, Maharashtra, India. Electronic address:

Topical sunscreen products are universally applied by numerous individuals to protect their skin from the detrimental effects of UV radiation. However, lately, studies have revealed the risks associated with percutaneous absorption of UV filters leading to undesirable systemic side effects such as hormonal disturbances and allergies. In this study, an innovative sunscreen formulation was developed based on starch microsponges as a key carrier encapsulating an organic sunscreen benzophenone‑3. The developed starch microsponges were characterized by scanning electron microscopy and nitrogen adsorption/desorption analysis. The results showed that starch microsponges possessed a high BET surface area (85.45 m/g) with spherical porous morphology with pore size <200 nm. Benzophenone‑3 was loaded into the starch microsponges by immersion/solvent evaporation and benzophenone‑3 loaded starch microsponges were characterized by scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy, and nitrogen adsorption-desorption measurements. Results corroborated that benzophenone‑3 was successfully entrapped within the nanopores of starch microsponges. A starch microsponge based sunscreen cream was formulated, characterized and clinically tested. Rheological, texture and sensorial assessment showed that starch microsponges based sunscreen product showed good spreadability, non-sticky, rich texture favorable for consumer usage. In vitro and ex-vivo studies demonstrated benzophenone‑3 loaded starch microsponges gave improved photoprotection, higher SPF and reduced cutaneous penetration compared to raw benzophenone‑3 cream. Clinically, patch study confirmed that the developed starch microsponges based sunscreen cream was skin safe and biocompatible. Thus, the amalgamation of sunscreen molecule benzophenone‑3 into starch microsponges produced a safe, effective innovative sunscreen product.
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http://dx.doi.org/10.1016/j.msec.2019.109882DOI Listing
November 2019

Preparation and Characterization of Solid Lipid Nanoparticles-Based Gel for Topical Delivery.

Methods Mol Biol 2019 ;2000:293-302

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India.

Solid lipid nanoparticles (SLNs) have been extensively investigated for effective delivery of both hydrophilic and lipophilic drugs by topical route. There are several scalable techniques for the preparation of SLNs such as homogenization, microemulsion template, and solvent emulsification diffusion. This chapter describes step-wise methodology for the preparation and characterization of SLNs using solvent emulsification diffusion method. Tretinoin, a lipophilic entity, was chosen as a model drug. The critical aspects and the important interpretations with respect to the preparation and characterization of SLNs are reported in "Notes" section.
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http://dx.doi.org/10.1007/978-1-4939-9516-5_20DOI Listing
March 2020

Fabrication of Nanostructured Lipid Carriers (NLC)-Based Gels from Microemulsion Template for Delivery Through Skin.

Methods Mol Biol 2019 ;2000:279-292

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, Maharashtra, India.

Nanostructured lipid carriers (NLC) represent the novel and widely explored generation of lipid nanoparticles. These are the second-generation solid lipid nanoparticles (SLN) developed with the aim to overcome limitations of SLN mainly with respect to limited drug loading and drug leakage during its storage. NLC are fabricated by mixing solid lipids with spatially incompatible (liquid) lipids leading to nanoparticulate structures with improved drug loading and controllable release properties. Out of the numerous methods reported to prepare NLC, microemulsion template (ME) technique is the most simple and preferred method. This methodology of preparation of lipid nanoparticles obviates the need for specialized equipment and energy to generate NLC, enables achieving desirable particle size of nanoparticles by modulating the size of the emulsion droplet, and is also feasible for easy scale-up. This chapter describes microemulsion template technique for fabrication of NLC based gel for topical delivery, particularly with respect to its method of preparation and product analysis.
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http://dx.doi.org/10.1007/978-1-4939-9516-5_19DOI Listing
March 2020

Preparation and Characterization of Micelles.

Methods Mol Biol 2019 ;2000:19-29

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India.

Nanoformulations in the past few decades have gained tremendous attention owing to their affirmative applications in increasing the bioavailability of poorly soluble drugs. Micelles in particular are favored due to their varied advantages which include thermodynamic stability, simple formulating steps, Newtonian flow, and enhanced biological barrier penetration. Owing to these advantages micellar nanosystems find extensive applications in oral, transdermal, and parenteral administration, and are now being explored for ocular and other noninvasive novel pathways of drug delivery such as nose to brain. In this chapter, we have discussed the protocol for the preparation of sumatriptan loaded micelles for the therapy of migraine. The inner core of these micelles comprises hydrophobic region of diblock polymer which holds the drug, while the hydrophilic region of the same provides conformational stability in the aqueous environment.
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http://dx.doi.org/10.1007/978-1-4939-9516-5_2DOI Listing
March 2020

Polymeric Mixed Micelles: Improving the Anticancer Efficacy of Single-Copolymer Micelles.

Crit Rev Ther Drug Carrier Syst 2019 ;36(1):1-58

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, Maharashtra, India.

Mixed micelles self-assembled from two or more dissimilar block copolymers provide a direct and convenient approach to improved drug delivery. The present review is focused on mixed micelles (prepared from block copolymers only) for various drug delivery applications along with their merits over single-copolymer micelles. Presented are the physicochemical properties of mixed and single-copolymer micelles, various stimuli-responsive mixed micelles for the treatment of cancer, interesting combinations of multifunctional mixed micelles along with their in vitro and in vivo performance, and the potential of mixed micelles as a gene delivery system. Finally, the performance of mixed micelles in preclinical and clinical testing is explained. In addition, the interaction of mixed micelles with cancer cells and the biosafety of mixed micelles are summarized. The in vitro and in vivo performance presented here clearly reveals that the mixed-micelle approach has a wider scope than that of the single-copolymer micelle approach and directs researchers to focus on this approach to delivery of drugs/gene/biologics for various applications.
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http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2018020481DOI Listing
January 2019

Polymeric Mixed Micelles: Improving the Anticancer Efficacy of Single-Copolymer Micelles.

Crit Rev Ther Drug Carrier Syst 2019 ;36(1):1-58

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai-400019, Maharashtra, India.

Mixed micelles self-assembled from two or more dissimilar block copolymers provide a direct and convenient approach to improved drug delivery. The present review is focused on mixed micelles (prepared from block copolymers only) for various drug delivery applications along with their merits over single-copolymer micelles. Presented are the physicochemical properties of mixed and single-copolymer micelles, various stimuli-responsive mixed micelles for the treatment of cancer, interesting combinations of multifunctional mixed micelles along with their in vitro and in vivo performance, and the potential of mixed micelles as a gene delivery system. Finally, the performance of mixed micelles in preclinical and clinical testing is explained. In addition, the interaction of mixed micelles with cancer cells and the biosafety of mixed micelles are summarized. The in vitro and in vivo performance presented here clearly reveals that the mixed-micelle approach has a wider scope than that of the single-copolymer micelle approach and directs researchers to focus on this approach to delivery of drugs/gene/biologics for various applications.
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http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.2018020481DOI Listing
June 2019

Crystal Engineering: Upcoming Paradigm for Efficacious Pulmonary Drug Delivery.

Curr Pharm Des 2018 ;24(21):2438-2455

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai, India.

Background And Objective: Pulmonary drug delivery has transformed over a past few decades from being a platform for local pulmonary disease treatment to systemic drug delivery opportunities. In case of pulmonary delivery systems, particle properties are critical as they affect inhalation efficacy, pulmonary deposition, drug delivery and overall performance. With this in view, particle engineering has emerged as an advanced science that helps in designing of efficacious pulmonary delivery systems. Among various particle engineering branches, crystal engineering is being extensively explored as it provides an opportunity to optimize particles at morphological, physicochemical and molecular levels which are essential to understand the role of crystal engineering in pulmonary drug delivery.

Methods: A thorough literature survey in the field of crystal engineering approaches explored for pulmonary drug delivery was conducted and the collected data was meticulously studied and summarized.

Results: In the review, pulmonary system is discussed with respect to various sites for drug deposition in respiratory tract, mechanism of drug deposition and clearance. Further, critical crystal parameters are discussed in-depth and various crystal engineering methods are summarized with emphasis on their impact on pulmonary delivery. Also, inhalation devices are overviewed to understand their performance in relation to crystal based pulmonary formulations.

Conclusion: The review enabled a detailed insight on crystal engineering approaches for design of pulmonary delivery systems.
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http://dx.doi.org/10.2174/1381612824666180518080948DOI Listing
October 2019

Curcumin Cocrystal Micelles-Multifunctional Nanocomposites for Management of Neurodegenerative Ailments.

J Pharm Sci 2018 04 26;107(4):1143-1156. Epub 2017 Nov 26.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga, Mumbai 400019, Maharashtra, India. Electronic address:

Curcumin, a potent antioxidant polyphenol with neuroprotective and antiamyloid activities, has significant potential in the treatment of neurodegenerative disorders such as Alzheimer's disease. However, its clinical translation is delayed due to poor bioavailability. For effective use of curcumin in Alzheimer's disease, it is imperative to increase its bioavailability with enhanced delivery at a therapeutic site that is, brain. With this objective, pharmaceutical cocrystals of curcumin were developed and incorporated in micellar nanocarriers for nose-to-brain delivery. For cocrystals, an antioxidant hydrophilic coformer was strategically selected using molecular modeling approach. The cocrystals were formulated using a planetary ball mill, and the process was optimized using 3 factorial design followed by characterization using differential scanning calorimetry, X-ray diffraction, and Fourier-transform infrared spectroscopy analysis. The cocrystal micelles exhibited globule size of 28.79 ± 0.86 nm. Further, curcumin cocrystal and co-crystal micelles exhibited a significantly low (p value <0.01) IC concentration for antioxidant activity as compared to curcumin corroborating superior antioxidant performance. In vivo studies revealed about 1.7-fold absolute bioavailability of curcumin cocrystal micelles with C of 1218.38 ± 58.11 ng/mL and showed significantly high brain distribution even beyond 6 hours of dosing. Thus, the studies confirmed enhanced bioavailability, higher brain uptake, retention, and delayed clearance with curcumin cocrystal micellar nanocarriers.
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http://dx.doi.org/10.1016/j.xphs.2017.11.014DOI Listing
April 2018

Medical capsule robots: A renaissance for diagnostics, drug delivery and surgical treatment.

J Control Release 2017 09 8;261:337-351. Epub 2017 Jul 8.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga East, Mumbai 400019, India. Electronic address:

The advancements in electronics and the progress in nanotechnology have resulted in path breaking development that will transform the way diagnosis and treatment are carried out currently. This development is Medical Capsule Robots, which has emerged from the science fiction idea of robots travelling inside the body to diagnose and cure disorders. The first marketed capsule robot was a capsule endoscope developed to capture images of the gastrointestinal tract. Today, varieties of capsule endoscopes are available in the market. They are slightly larger than regular oral capsules, made up of a biocompatible case and have electronic circuitry and mechanisms to capture and transmit images. In addition, robots with diagnostic features such as in vivo body temperature detection and pH monitoring have also been launched in the market. However, a multi-functional unit that will diagnose and cure diseases inside the body has not yet been realized. A remote controlled capsule that will undertake drug delivery and surgical treatment has not been successfully launched in the market. High cost, inadequate power supply, lack of control over drug release, limited space for drug storage on the capsule, inadequate safety and no mechanisms for active locomotion and anchoring have prevented their entry in the market. The capsule robots can revolutionize the current way of diagnosis and treatment. This paper discusses in detail the applications of medical capsule robots in diagnostics, drug delivery and surgical treatment. In diagnostics, detailed analysis has been presented on wireless capsule endoscopes, issues associated with the marketed versions and their corresponding solutions in literature. Moreover, an assessment has been made of the existing state of remote controlled capsules for targeted drug delivery and surgical treatment and their future impact is predicted. Besides the need for multi-functional capsule robots and the areas for further research have also been highlighted.
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http://dx.doi.org/10.1016/j.jconrel.2017.07.005DOI Listing
September 2017

Porous microscaffolds for 3D culture of dental pulp mesenchymal stem cells.

Int J Pharm 2016 Dec 27;515(1-2):555-564. Epub 2016 Oct 27.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai 400019, Maharashtra, India. Electronic address:

The collective power of stem cells due to their evident advantages is incessantly investigated in regenerative medicine to be the next generation exceptional remedy for tissue regeneration and treatment of diseases. Stem cells are highly sensitive and a 3D culture environment is a requisite for its successful transplantation and integration with tissues. Porous microscaffolds can create a 3D microenvironment for growing stems cells, controlling their fate both in vitro and in vivo. In the present study, interconnected porous PLGA microscaffolds were fabricated, characterized and employed to propagate human dental pulp mesenchymal stem cells (DPMSCs) in vitro. The porous topography was investigated by scanning electron microscopy and the pore size was controlled by fabrication conditions such as the concentration of porogen. DPMSCs were cultured on microscaffolds and were evaluated for their morphology, attachment, proliferation, cell viability via MTT and molecular expression (RT-PCR). DPMSCs were adequately proliferated and adhered over the microscaffolds forming a 3D cell-microscaffold construct. The average number of DPMSCs grown on PLGA microscaffolds was significantly higher than monolayer 2D culture during 5th and 7th day. Moreover, cell viability and gene expression results together corroborated that microscaffolds maintained the viability, stemness and plasticity of the cultured dental pulp mesenchymal stem cells. The novel porous microscaffold developed acts as promising scaffold for 3D culture and survival and transplantation of stem cells for tissue engineering.
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http://dx.doi.org/10.1016/j.ijpharm.2016.10.040DOI Listing
December 2016

Performance Parameters and Characterizations of Nanocrystals: A Brief Review.

Pharmaceutics 2016 Aug 30;8(3). Epub 2016 Aug 30.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai-400019, India.

Poor bioavailability of drugs associated with their poor solubility limits the clinical effectiveness of almost 40% of the newly discovered drug moieties. Low solubility, coupled with a high log p value, high melting point and high dose necessitates exploration of alternative formulation strategies for such drugs. One such novel approach is formulation of the drugs as "Nanocrystals". Nanocrystals are primarily comprised of drug and surfactants/stabilizers and are manufactured by "top-down" or "bottom-up" methods. Nanocrystals aid the clinical efficacy of drugs by various means such as enhancement of bioavailability, lowering of dose requirement, and facilitating sustained release of the drug. This effect is dependent on the various characteristics of nanocrystals (particle size, saturation solubility, dissolution velocity), which have an impact on the improved performance of the nanocrystals. Various sophisticated techniques have been developed to evaluate these characteristics. This article describes in detail the various characterization techniques along with a brief review of the significance of the various parameters on the performance of nanocrystals.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039445PMC
http://dx.doi.org/10.3390/pharmaceutics8030026DOI Listing
August 2016

Teratogenicity of Artemether-Clindamycin Nanostructured Lipid Carriers in Rats.

Int J Toxicol 2016 07 8;35(4):420-8. Epub 2016 Jun 8.

Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, Maharashtra, India.

Currently, artemisinin-based combination therapy is considered the best option in the treatment of malaria. However, toxicity of artemisinins limits their use in pregnancy. In the absence of sufficient toxicity data, the World Health Organization recommends that artemisinins are not to be used in the first trimester of pregnancy and can be used only in second and third trimesters, when other treatments are not available. We have recently observed that drugs loaded in nanolipid carriers are selectively taken up in Plasmodium-infected erythrocytes with a concomitant reduction in the dose required to cure animals. Thus, 20% of the therapeutic dose of artemether-clindamycin (ARM-CP) loaded in nanostructured lipid carriers (NLCs; mean particle size 55 ± 10 nm) resulted in complete parasite clearance and 100% survival of infected mice. Here, we investigate the teratogenicity of this formulation in rodents (dosing on alternate days from 6th day to 18th day of gestation; 12-15 animals/group). The teratogenicity of drug-free NLCs and artesunate-clindamycin (ARS-CP) solution was also evaluated. We found that the therapeutic dose of ARS-CP caused fetal resorptions (87.5% resorptions in 8 litters), suggesting its unsuitability for use in pregnancy. Artesunate-clindamycin NLCs at therapeutic doses also resulted in ∼90% fetal resorptions in 10 litters examined. However, postimplantation losses or fetal malformations were not observed at the dose of ARM-CP NLCs that was required for complete parasite clearance in preclinical trials (ie, 20% of the therapeutic dose). Our data suggest that the NLCs loaded with 20% of the therapeutic dose of ARM-CP may have potential in treating malaria during pregnancy.
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http://dx.doi.org/10.1177/1091581816652605DOI Listing
July 2016

Solid lipid nanoparticles of amphotericin B (AmbiOnp): in vitro and in vivo assessment towards safe and effective oral treatment module.

Drug Deliv Transl Res 2016 08;6(4):354-64

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai, 400019, Maharashtra, India.

Amphotericin B, a gold standard broad spectrum antibiotic used in treatment of systemic fungal infections and visceral leishmaniasis, though is effective parenterally offers severe nephrotoxicity whereas the oral delivery is reported to give very meager oral bioavailability. Thus, to alleviate the toxicity and to improve oral bioavailability, an effective oral delivery approach in the form of solid lipid nanoparticles of amphotericin B (AmbiOnp) was reported earlier by our group. In this investigation, we report the predominant formation of nontoxic superaggregated form of amphotericin B, resulting from the probe sonication-assisted nanoprecipitation technique. The developed formulation was further confirmed to retain this nontoxic form and was found to be stable over the varied gastrointestinal conditions. Further, in vitro antifungal activity of AmbiOnp against Candida albicans showed minimum inhibitory concentration value of 7.812 μg/mL attributed to controlled release of drug from nanoparticulate matrix. In vivo pharmacokinetic studies revealed a relative bioavailability of AmbiOnp to be 1.05-fold with a Cmax of 1109.31 ± 104.79 ng/mL at the end of 24 h which was comparable to Cmax of 1417.49 ± 85.52 ng/mL achieved with that of marketed formulation (Fungizone®) given intravenously establishing efficacy of AmbiOnp. In vivo biodistribution studies indicated very low levels of Amphotericin B in kidneys when given as AmbiOnp as compared to that of marketed formulation proving its safety and was further corroborated by renal toxicity studies. Further, the formulations were found to be stable under refrigeration condition over a period of 3 months.
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http://dx.doi.org/10.1007/s13346-015-0267-6DOI Listing
August 2016

Transungual permeation: current insights.

Drug Deliv Transl Res 2016 08;6(4):426-39

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, N.P. Marg, Matunga (E), Mumbai, 400019, Maharashtra, India.

Nail disorders are beyond cosmetic concern; besides discomfort in the performance of daily chores, they disturb patients psychologically and affect their quality of life. Fungal nail infection (onychomycosis) is the most prevalent nail-related disorder affecting a major population worldwide. Overcoming the impenetrable nail barrier is the toughest challenge for the development of efficacious topical ungual formulation. Sophisticated techniques such as iontophoresis and photodynamic therapy have been proven to improve transungual permeation. This article provides an updated and concise discussion regarding the conventional approach and upcoming novel approaches focused to alter the nail barrier. A comprehensive description regarding preformulation screening techniques for the identification of potential ungual enhancers is also described in this review while highlighting the current pitfalls for the development of ungual delivery.
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http://dx.doi.org/10.1007/s13346-015-0259-6DOI Listing
August 2016

A Special Section on Nanophytomedicine.

J Nanosci Nanotechnol 2015 Jun;15(6):4019-20

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http://dx.doi.org/10.1166/jnn.2015.10653DOI Listing
June 2015

Colloidal soft nanocarrier for transdermal delivery of dopamine agonist: ex vivo and in vivo evaluation.

J Biomed Nanotechnol 2014 Nov;10(11):3291-303

Ropinirole, an antiparkinsoism dopamine agonist, is used to treat Restless Legs Syndrome. However, orally it undergoes degradation in gastrointestinal tract and extensive first pass metabolism, resulting in its poor and variable bioavailability of the commercially available oral tablets. In the present investigation, soft nanocarriers, viz., microemulsion of ropinirole with the globule size of 160.2 ± 3.87 nm and zeta potential of -4.24 mV was explored for transdermal application. Transdermal drug delivery offers benefits such as sustained therapeutic plasma levels of drugs, avoidance of first pass effect, and improved patient compliance. In comparison to the hydrogel, the developed microemulsion enhanced the drug permeation across the rat skin and porcine ear skin by 3.5 and 2 folds, respectively. Further, the developed microemulsion antagonized the catalepsy in the haloperidol-induced catalepsy rat model by 10 folds as compared to the marketed tablets. Additionally, in rotenone induced Parkinsonism rat model, the microemulsion showed improvement in the motor function by 76% whereas the oral tablet showed only 5% restoration of the normal function. Besides this, the developed formulation successfully restored the catalase and superoxide dismutase levels which were significantly reduced by rotenone administration. Overall, the in vivo studies suggested the potential of the developed transdermal microemulsion of Ropinirole as a viable alternative to marketed formulations.
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http://dx.doi.org/10.1166/jbn.2014.1857DOI Listing
November 2014

Pulmonary multifunctional nano-oncological modules for lung cancer treatment and prevention.

J Biomed Nanotechnol 2014 Sep;10(9):1863-93

Mortality associated with lung cancer and its metastasis has outnumbered those related to other forms of cancer. Despite being a directly accessible organ, conventional oncological strategies exhibiting prolific outcome in treatment and prevention of lung cancer is far from reality. This is attributed to numerous challenges posed by lung environment. The extracellular aura of lung comprises immensely complicated structures, ciliary escalators, omnipresence of mucus and alveolar fluid, and macrophagial uptake which presents an array of impediments to the arrival of therapeutic moiety at the tumor site. Besides these, intracellular obstacles viz enzymatic degradation, cell membrane translocation, endosomal escape and/or nuclear entry also limit superior therapeutic efficacy. The current review elaborates wide-ranging challenges to lung cancer treatment and its circumvention by latest developments in multifunctional nano-oncological modules delivered via the pulmonary route-which smartly deal with the abovementioned issues and bestow positivity to this complication.
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http://dx.doi.org/10.1166/jbn.2014.1900DOI Listing
September 2014

Development of immunochromatographic strip test using fluorescent, micellar silica nanosensors for rapid detection of B. abortus antibodies in milk samples.

Biosens Bioelectron 2015 Aug 20;70:254-60. Epub 2015 Mar 20.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Matunga, Mumbai 400019, India. Electronic address:

Presence of bacteria such as Brucella spp. in dairy products is an immense risk to public health. Point of care immunoassays are rapid in that they can quickly screen various samples in a relatively short amount of time, are sensitive, specific and offer a great advantage in accurate and fast diagnosis of infectious diseases. We have fabricated a point of care rapid diagnostic assay that employs fluorescent, micellar silica nanosensors capable of specifically detecting Brucella IgG antibodies in milk samples of afflicted animals. Currently, point of care detection assays are not commercially available for field testing of farm animals using milk samples. The nanosensing allows precise detection of antibodies with low sample volumes (50 μl). We demonstrate recognition of B. abortus antibodies through capture by fluorescent silica nanosensors using spiked and raw milk samples validated by ELISA and PCR. The test results are accurate and repeatable with high sensitivity and specificity, and a short assay time of 10 min for antigenic recognition and do not require any sample processing procedures such as isolation and separation. Additionally, well defined antigenic components and surface biomarkers of various disease causing microbes can be broadly incorporated within the purview of this technology for accurate and rapid detection of suspected bovine pathological conditions, and can largely enable rapid field testing that can be implemented in farms and food industry.
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http://dx.doi.org/10.1016/j.bios.2015.03.045DOI Listing
August 2015

Polymeric nanoparticles for targeted treatment in oncology: current insights.

Int J Nanomedicine 2015 2;10:1001-18. Epub 2015 Feb 2.

Department of Pharmaceutical Sciences, Chicago College of Pharmacy, Midwestern University, Downers Grove, IL, USA.

Chemotherapy, a major strategy for cancer treatment, lacks the specificity to localize the cancer therapeutics in the tumor site, thereby affecting normal healthy tissues and advocating toxic adverse effects. Nanotechnological intervention has greatly revolutionized the therapy of cancer by surmounting the current limitations in conventional chemotherapy, which include undesirable biodistribution, cancer cell drug resistance, and severe systemic side effects. Nanoparticles (NPs) achieve preferential accumulation in the tumor site by virtue of their passive and ligand-based targeting mechanisms. Polymer-based nanomedicine, an arena that entails the use of polymeric NPs, polymer micelles, dendrimers, polymersomes, polyplexes, polymer-lipid hybrid systems, and polymer-drug/protein conjugates for improvement in efficacy of cancer therapeutics, has been widely explored. The broad scope for chemically modifying the polymer into desired construct makes it a versatile delivery system. Several polymer-based therapeutic NPs have been approved for clinical use. This review provides an insight into the advances in polymer-based targeted nanocarriers with focus on therapeutic aspects in the field of oncology.
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http://dx.doi.org/10.2147/IJN.S56932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4324541PMC
May 2016

Parasite impairment by targeting Plasmodium-infected RBCs using glyceryl-dilaurate nanostructured lipid carriers.

Biomaterials 2014 Aug 10;35(24):6636-45. Epub 2014 May 10.

Department of Biological Sciences, Tata Institute of Fundamental Research, Mumbai, India.

Antimalarial therapy is a major contributor to declining malaria morbidity and mortality. However, the high toxicity and low bioavailability of current antimalarials and emerging drug resistance necessitates drug-delivery research. We have previously developed glyceryl-dilaurate nanolipid carriers (GDL-NLCs) for antimalarial drug delivery. Here, we show evidence that GDL-NLCs themselves selectively target Plasmodium-infected red blood cells (iRBCs), and cause severe parasite impairment. The glyceryl-dilaurate lipid-moiety was important in the targeting. GDL-NLCs localized to the parasite mitochondrion and uptake led to mitochondrial-membrane polarization and Ca(2+) ion accumulation, ROS release, and stage-specific iRBC lysis. GDL-NLC treatment also resulted in externalization of iRBC-membrane phosphatidylserine and enhanced iRBC clearance by macrophages. GDL-NLC uptake disrupted the parasite-induced tubulovesicular network, which is vital for nutrient import by the parasite. Laser optical trap studies revealed that GDL-NLCs also restored iRBC flexibility. Such restoration of iRBC flexibility may help mitigate the vasculature clogging that can lead to cerebral malaria. We demonstrate the suitability of GDL-NLCs for intravenous delivery of antimalarial combinations artemether-clindamycin and artemether-lumefantrine in the murine model. Complete parasite clearance was achieved at 5-20% of the therapeutic dose of these combinations. Thus, this nanostructured lipid formulation can solubilize lipophilic drugs, selectively target and impair the parasite-infected red cell, and therefore constitutes a potent delivery vehicle for antimalarials.
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http://dx.doi.org/10.1016/j.biomaterials.2014.04.058DOI Listing
August 2014

Endosomal escape: a bottleneck in intracellular delivery.

J Nanosci Nanotechnol 2014 Jan;14(1):460-74

With advances in therapeutic science, apart from drugs, newer bioactive moieties like oligonucleotides, proteins, peptides, enzymes and antibodies are constantly being introduced for the betterment of therapeutic efficacy. These moieties have intracellular components of the cells like cytoplasm and nucleus as one of their pharmacological sites for exhibiting therapeutic activity. Despite their promising efficacy, their intracellular bioavailability has been critically hampered leading to failure in the treatment of numerous diseases and disorders. The endosomal uptake pathway is known to be a rate-limiting barrier for such systems. Bioactive molecules get trapped in the endosomal vesicles and degraded in the lysosomal compartment, necessitating the need for effective strategies that facilitate the endosomal escape and enhance the cytosolic bioavailability of bioactives. Microbes like viruses and bacteria have developed their innate mechanistic tactics to translocate their genome and toxins by efficiently penetrating the host cell membrane. Understanding this mechanism and exploring it further for intracellular delivery has opened new avenues to surmount the endosomal barrier. These strategies include membrane fusion, pore formation and proton sponge effects. On the other hand, progress in designing a novel smart polymeric carrier system that triggers endosomal escape by undergoing modulations in the intracellular milieu has further led to an improvement in intracellular delivery. These comprise pH, enzyme and temperature-induced modulators, synthetic cationic lipids and photo-induced physical disruption. Each of the aforementioned strategies has its own unique mechanism to escape the endosome. This review recapitulates the numerous strategies designed to surmount the bottleneck of endosomal escape and thereby achieve successful intracellular uptake of bioactives.
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http://dx.doi.org/10.1166/jnn.2014.9082DOI Listing
January 2014

Tamoxifen nanostructured lipid carriers: enhanced in vivo antitumor efficacy with reduced adverse drug effects.

Int J Pharm 2014 Jul 2;468(1-2):1-14. Epub 2014 Apr 2.

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, University under Section 3 of UGC Act-1956, Elite Status and Center of Excellence-Government of Maharashtra, Matunga (E), Mumbai, Maharashtra 400019, India. Electronic address:

A novel approach of enhancing the Tamoxifen uptake via Intestinal Lymphatic System is executed by developing long chain lipid and oil based nanostructured lipid carrier system (Tmx-NLC). The aim was to achieve improved systemic bioavailability of Tamoxifen, prevent systemic and hepatotoxicity and enhance antitumor efficacy. Following the proof of concept achieved in cell culture experiments and in vivo pharmacokinetic and biodistribution study, the current work focuses on investigation of antitumor efficacy and treatment associated toxicity in murine mammary tumor mice model. The efficacy study demonstrated greater tumor suppression and 100% survival with 1.5 and 3 mg/kg Tmx-NLC compared to 3 mg/kg Tamoxifen suspension and Mamofen(®) (Khandelwal Pharmaceuticals, Mumbai, India). Tmx-NLC treatment for a month demonstrated improved systemic toxicity profile and no evidences of hepatotoxicity. Thus, developed Tmx-NLC could prove to be a promising delivery strategy to confer superior therapeutic efficacy and ability to address the biopharmaceutical and toxicity associated issues of drug.
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http://dx.doi.org/10.1016/j.ijpharm.2014.03.056DOI Listing
July 2014

Controlled iontophoretic delivery of pramipexole: electrotransport kinetics in vitro and in vivo.

Eur J Pharm Biopharm 2014 Sep 11;88(1):56-63. Epub 2014 Feb 11.

School of Pharmaceutical Sciences, University of Geneva & University of Lausanne, Geneva, Switzerland. Electronic address:

The objective of the study was to investigate the anodal iontophoretic delivery of pramipexole (PRAM), a dopamine agonist used for the treatment of Parkinson's disease, in order to determine whether therapeutic amounts of the drug could be delivered across the skin. Preliminary iontophoretic experiments were performed in vitro using porcine ear and human abdominal skin. These were followed by a pharmacokinetic study in male Wistar rats to determine the drug input rate in vivo. Stability studies revealed that after current application (0.5 mA/cm(2) for 6h), the solution concentration of PRAM was only 60.2 ± 5.3% of its initial value. However, inclusion of sodium metabisulfite (0.5%), an antioxidant, increased this to 97.2 ± 3.1%. Iontophoretic transport of PRAM across porcine skin in vitro was studied as a function of current density (0.15, 0.3, 0.5 mA/cm(2)) and concentration (10, 20, 40 mM). Increasing the current density from 0.15 to 0.3 and 0.5 mA/cm(2), resulted in 2.5- and 4-fold increases in cumulative permeation, from 309.5 ± 80.2 to 748.8 ± 148.1 and 1229.1 ± 138.6 μg/cm(2), respectively. Increasing the PRAM concentration in solution from 10 to 20 and 40 mM resulted in a 2-fold increase in cumulative permeation (816.4 ± 123.3, 1229.1 ± 138.6 and 1643.6 ± 201.3 μg/cm(2), respectively). Good linearity was observed between PRAM flux and both the applied current density (r(2)=0.98) and drug concentration in the formulation (r(2)=0.99). Co-iontophoresis of acetaminophen showed that electromigration was the dominant electrotransport mechanism (accounting for >80% of delivery) and that there was no inhibition of electroosmotic flow at any current density. Cumulative iontophoretic permeation across human and porcine skin (after 6h at 0.5 mA/cm(2)) was also shown to be statistically equivalent (1229.1 ± 138.6 and 1184.8 ± 236.4 μg/cm(2), respectively). High transport and delivery efficiencies were achieved for PRAM (up to 7% and 58%, respectively). The plasma concentration profiles obtained in the iontophoretic studies in vivo (20 mM PRAM; 0.5 mA/cm(2) for 5h) were modelled using constant and time-variant input models; the latter gave a superior quality fit. The drug input rate in vivo suggested that PRAM electrotransport rates would be sufficient for therapeutic delivery and the management of Parkinsonism.
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http://dx.doi.org/10.1016/j.ejpb.2014.02.002DOI Listing
September 2014

Nanocoatings on implantable medical devices.

Pharm Pat Anal 2013 Jul;2(4):499-512

Department of Pharmaceutical Sciences & Technology, Institute of Chemical Technology, Matunga, Mumbai - 400019, India.

The global medical device industry has experienced significant growth over the past 5 years. The surge of patent publications in the field bears testimony to this fact. The advent of nanotechnology has opened up newer unexplored vistas in the field of medical devices. This review summarizes patents employing the principles of nanotechnology in the formulation of coatings for implantable medical devices. Patents selected have at least one entity or structure with dimensions in the nanometer range, which results in a therapeutic value addition. The strategies reviewed pertain to tackling issues such as restenosis and thrombosis in addition to improving the overall acceptability of the implantable medical device, particularly those placed in the vasculature.
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http://dx.doi.org/10.4155/ppa.13.30DOI Listing
July 2013

Nanomedicine-prospects and challenges.

Drug Deliv Transl Res 2013 Oct;3(5):381

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology (Deemed University), Mumbai, India,

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http://dx.doi.org/10.1007/s13346-013-0144-0DOI Listing
October 2013

Controlled iontophoretic transport of huperzine A across skin in vitro and in vivo: effect of delivery conditions and comparison of pharmacokinetic models.

Mol Pharm 2013 Nov 30;10(11):4322-9. Epub 2013 Sep 30.

School of Pharmaceutical Sciences, University of Geneva & University of Lausanne , 30 Quai Ernest Ansermet, 1211 Geneva, Switzerland.

The aim of this study was to investigate constant current anodal iontophoresis of Huperzine A (HupA) in vitro and in vivo and hence to evaluate the feasibility of using electrically assisted delivery to administer therapeutic amounts of the drug across the skin for the treatment of Alzheimer's disease. Preliminary experiments were performed using porcine and human skin in vitro. Stability studies demonstrated that HupA was not degraded upon exposure to epidermis or dermis for 12 h and that it was also stable in the presence of an electric current (0.5 mA · cm(-2)). Passive permeation of HupA (2 mM) was minimal (1.1 ± 0.1 μg · cm(-2)); iontophoresis at 0.15, 0.3, and 0.5 mA · cm(-2) produced 106-, 134-, and 184-fold increases in its transport across the skin. Surprisingly, despite the use of a salt bridge to isolate the formulation compartment from the anodal chamber, which contained 133 mM NaCl, iontophoresis of HupA was shown to increase linearly with its concentration (1, 2, and 4 mM in 25 mM MES, pH 5.0) (r(2) = 0.99). This was attributed to the low ratio of drug to Cl¯ (in the skin and in the receiver compartment) which competed strongly to carry current, its depletion, and to possible competition from the zwitterionic MES. Co-iontophoresis of acetaminophen confirmed that electromigration was the dominant electrotransport mechanism. Total delivery across human and porcine skin was found to be statistically equivalent (243.2 ± 33.1 and 235.6 ± 13.7 μg · cm(-2), respectively). Although the transport efficiency was ∼ 1%, the iontophoretic delivery efficiency (i.e., the fraction of the drug load delivered) was extremely high, in the range of 46-81% depending on the current density. Cumulative permeation of HupA from a Carbopol gel formulation after iontophoresis for 6 h at 0.5 mA · cm(-2) was less than that from solution (135.3 ± 25.2 and 202.9 ± 5.2 μg · cm(-2), respectively) but sufficient for therapeutic delivery. Pharmacokinetic parameters were determined in male Wistar rats in vivo (4 mM HupA; 0.5 mA · cm(-2) for 5 h with Ag/AgCl electrodes) using two-compartment models with either constant or time-variant input rates. A superior fit was obtained using the time-variant model, and the input rate in vivo was significantly greater than that in vitro. Based on these results and the known pharmacokinetics, it was estimated that therapeutic amounts of HupA could be delivered for the treatment of Alzheimer's disease using a reasonably sized patch.
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http://dx.doi.org/10.1021/mp4004173DOI Listing
November 2013

Psoriasis clinical implications and treatment: a review.

Crit Rev Ther Drug Carrier Syst 2013 ;30(3):183-216

Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Nathalal Parekh Marg, Matunga, Mumbai 400 019, India.

Psoriasis is a common skin disorder affecting the population worldwide. It is a T-cell mediated autoimmune disorder leading to keratinocyte hyperproliferation. Psoriasis has genetic predisposition that is further aggravated by certain stimulating factors. In spite of significant advances in understanding the pathogenesis of psoriasis, the exact etiology of the disease remains unknown. The clinical manifestations of this disease include various forms that affect different parts of the body. Treatment options vary according to the mode of application or severity of the disease. Earlier treatments have included application of emollients or keratolytic agents to hydrate the skin or shed off the skin. But later treatments have been modified to treat the underlying T-cell proliferation. Hence, topical treatments like coal tar, vitamin D, retinoids, topical calcineurin inhibitors for treating mild psoriasis, systemic treatments including methotrexate, cyclosporine, acitretin, hydroxyurea, as well as light therapy for severe psoriasis have become more prominent. Current treatment modalities are associated with the risk of serious side effects from prolonged treatment. Combinations of these therapies have provided effective and rapid modalities to suppress the disease and reduce the side effects of treatment. In addition, newer carrier systems for conventional drugs are being developed to improve the effectiveness of treatment and reduce the side effects. Development of biologics and gene therapy have revolutionized the treatment of this skin disease. Although an array of therapies to suppress the psoriatic condition exists, none are curative.
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http://dx.doi.org/10.1615/critrevtherdrugcarriersyst.2013005268DOI Listing
October 2013