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Paliwal S.R.,Drug Delivery Research Laboratory | Paliwal R.,Drug Delivery Research Laboratory | Agrawal G.P.,Pharmaceutics Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Nanomedicine | Year: 2011

Liposomes are well-established nanocarriers for improving the therapeutic index of anticancer agents. A remarkable understanding in the pathophysiology of breast cancer progression has emerged with information on the involved specific biomolecules, which may serve as molecular targets for its therapy. Hormonal and nonhormonal receptors can both be exploited for targeting to breast cancer cells. Targeted delivery of cytotoxic drugs using liposomes is a novel approach for breast cancer therapy. In the present article, we summarize molecular targets present on the breast cancer cells. Recent developments in liposome-based delivery of bioactives for selective treatments of breast cancer are discussed. In addition, utilization of bioenvironmental conditions of tumor for liposome-based targeted delivery is also summed up. © 2011 Future Medicine Ltd.


Paliwal R.,Drug Delivery Research Laboratory | Paliwal S.R.,Drug Delivery Research Laboratory | Agrawal G.P.,Pharmaceutics Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Molecular Pharmaceutics | Year: 2011

Low molecular weight heparin (LMWH) is an anionic oligosaccharide macromolecule, which is commonly administered via parenteral routes for the treatment of vascular disorders like deep vein thrombosis (DVT) and pulmonary embolism (PE). Oral heparin delivery can tremendously improve the treatment of such disorders but is restricted due to its large size and anionic character. The present investigation describes synthesis of LMWH-lipid conjugates and their encapsulation in phosphatidylcholine stabilized biomimetic solid lipid nanoparticles (SLNs) for LMWH's oral bioavailability enhancement. Briefly, LMWH was conjugated with different saturated lipids of varying chain length (stearic acid, palmitic acid and myristic acid) using carbodiimide chemistry. The conjugation was confirmed with IR and 1H NMR spectroscopy. The LMWH-lipid conjugate loaded SLNs were characterized for various parameters like shape, size, zeta potential, entrapment efficiency and in vitro release behavior in different simulated GIT pH mediums. The GIT toxicity of LMWH-lipid conjugate loaded SLNs to different tissues of intestinal epithelium was observed using H&E staining followed by microscopic observation at cellular level. The LMWH-lipid conjugate loaded SLNs were found to be safe for oral administration. The plasma concentration of LMWH was estimated using anti-FXa chromogenic assay. A significantly higher bioavailability (p < 0.05) of LMWH was observed using LMWH-lipid conjugates loaded SLNs in comparison to LMWH loaded SLNs and free LMWH. The order of different conjugates in bioavailability enhancement was LMWH-stearic acid > LMWH-palmitic acid > LMWH-myristic acid. This strategy holds promise for future applications of oral delivery of LMWH conjugates in the form of SLNs particularly for the treatment of cardiovascular disease like DVT and PE. © 2011 American Chemical Society.


Tiwari S.,Drug Delivery Research Laboratory | Agrawal G.P.,Drug Delivery Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Nanomedicine | Year: 2010

The mucosal immune system, the primary portal for entry of most prevalent and devastating pathogens, is guarded by the special lymphoid tissues (mucosally associated lymphoid tissues) for immunity. Mucosal immune infection results in induction of IgA-manifested humoral immunity. Cell-mediated immunity may also be generated, marked by the presence of CD4+ Th1 and CD8+ cells. Furthermore, the immunity generated at the mucosal site is transported to the distal mucosal site as well as to systemic tissues. An understanding of the molecular basis of the mucosal immune system provides a unique platform for designing a mucosal vaccine. Coadministration of immunostimulatory molecules further accelerates functioning of the immune system. Mimicking receptor-mediated binding of the pathogen may be achieved by direct conjugation of antigen with an immunostimulatory molecule or encapsulation in a carrier followed by anchoring of a ligand having affinity to the cells of the mucosal immune system. Nanotechnology has played a significant role in mucosal vaccine development and among the available options liposomes are the most promising. Liposomes are phospholipid bilayered vesicles that can encapsulate protein as well as DNA-based vaccines and offer coencapsulation of adjuvant along with the antigen. At the same, time ligand-conjugated liposomes augment interaction of antigen with the cells of the mucosal immune system and thereby serve as suitable candidates for the mucosal delivery of vaccines. This article exhaustively explores strategies involved in the generation of mucosal immunity and also provides an insight to the progress that has been made in the development of liposome-based mucosal vaccine. © 2010 Future Medicine Ltd.


Sharma R.,Drug Delivery Research Laboratory | Agrawal U.,Drug Delivery Research Laboratory | Mody N.,Drug Delivery Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Biotechnology Advances | Year: 2015

Mucosal sites serve as the main portal for the entry of pathogens and thus immunization through mucosal routes can greatly improve the immunity. Researchers are continuously exploring the vaccination strategies to engender protective mucosal immune responses. Unearthing of mucosal adjuvants, that are safe and effective, is enhancing the magnitude and quality of the protective immune response. Use of nanotechnology based polymeric nanocarrier systems which encapsulate vaccine components for protection of sensitive payload, incorporate mucosal adjuvants to maximize the immune responses and target the mucosal immune system is a key strategy to improve the effectiveness of mucosal vaccines. These advances promise to accelerate the development and testing of new mucosal vaccines against many human diseases. This review focuses on the need for the development of nanocarrier based mucosal vaccines with emphases on the polymeric nanoparticles, their clinical status and future perspectives. This review focuses on the need and new insights for the development of nanoarchitecture governed mucosal vaccination with emphases on the various polymeric nanoparticles, their clinical status and future perspectives. © 2014 Elsevier Inc.


Agrawal U.,Drug Delivery Research Laboratory | Sharma R.,Drug Delivery Research Laboratory | Gupta M.,Drug Delivery Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Drug Discovery Today | Year: 2014

The oral route for drug delivery is regarded as the optimal route for achieving therapeutic benefits owing to increased patient compliance. Despite phenomenal advances in injectable, transdermal, nasal and other routes of administration, the reality is that oral drug delivery remains well ahead of the pack as the preferred delivery route. Nanocarriers can overcome the major challenges associated with this route of administration: mainly poor solubility, stability and biocompatibility of drugs. This review focuses on the potential of various polymeric drug delivery systems in oral administration, their pharmacokinetics, in vitro and in vivo models, toxicity and regulatory aspects. © 2014 Elsevier Ltd. All rights reserved.


Gupta M.,Drug Delivery Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Chemistry and Physics of Lipids | Year: 2012

The nanoparticulate carrier systems as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have gained interest for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Therefore in this study, SLNs and NLCs loaded fluconazole (FLZ) were prepared by solvent diffusion method in an aqueous system and characterized for different parameters. In addition, antifungal activity was carried out on experimentally induced cutaneous candidiasis in immunosuppressed albino rats. The results showed that SLNs and NLCs represent the respective mean particle sizes of approx. 178 and 134 nm with encapsulation efficiency of 75.7 ± 4.94% and 81.4 ± 3.89%, respectively. The skin-retention studies of FLZ from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of NLCs formulation. The in vivo cumulative amount of FLZ retention from NLCs was more than 5-fold that of the plain solution, while it was 3.3-fold more in the case of an equivalent-dose application in the form of SLNs at 12 h after administration. The antifungal study also confirmed the maximum therapeutic efficacy of NLCs, as the lowest number of cfu/ml was recorded. It can be concluded from this study that NLCs provide a good skin targeting effect and may be a promising carrier for topical delivery of FLZ offering the sustained release and maintain the localized effect, resulting in an effective treatment of a life-threatening cutaneous fungal infection. © 2012 Elsevier Ireland Ltd.


Gupta M.,Drug Delivery Research Laboratory | Agrawal G.P.,Drug Delivery Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Current Molecular Medicine | Year: 2013

Inspite of demanding research that has been undertaken for cancer treatment, cancer is a major cause of mortality. Available conventional treatment options of solid tumor are associated with serious side effects. Nanomedicines mediated fascinating approach may be effectively utilized for efficient tumor targeting by avoiding all the problems associated with conventional chemotherapy. Polymeric nanomedicines such as polymer micelles, polymeric nanoparticles, polymersomes and polymer conjugates currently developed for solid tumor treatment have proved to be efficacious cancer therapeutics. These polymeric nanostructures are able to reach tumor tissue or angiogenic endothelial cells either passively or actively. To date, more advancement in the tumor targeting field includes stimuli sensitive polymeric nanocarriers that pass through the intracellular delivery barriers and release the bioactives in response to the microenvironmental trigger of tumor cell. This review discusses the molecular aspects of solid tumor pathophysiology and its dramatic impact on research for innovative and novel therapeutic approaches linked with tumor-targeting polymeric nanomedicines. © 2013 Bentham Science Publishers.


Paliwal R.,Drug Delivery Research Laboratory | Rai S.,Drug Delivery Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Journal of Biomedical Nanotechnology | Year: 2011

The objective of the study was to develop lipid drug conjugate nanoparticles (LDC-NPs) of anticancer drug methotrexate (MTX) for oral delivery that faces problems of low and variable bioavailability. The MTX loaded LDC-NPs significantly enhanced bioavailability and reduced MTX associated gastrointestinal toxicity even in higher doses recommended for anticancer therapy. Copyright © 2011 American Scientific Publishers All rights reserved.


Rai S.,Drug Delivery Research Laboratory | Paliwal R.,Drug Delivery Research Laboratory | Vyas S.P.,Drug Delivery Research Laboratory
Journal of Biomedical Nanotechnology | Year: 2011

The encapsulation of anticancer agent in carrier system protects healthy tissues from its cytotoxic effects. In the present study estrogen receptor targeted liposomes encapsulating doxorubicin was designed to enhance the efficiency of delivery of doxorubicin to its destination site. The liposomal formulations showed change in the biodistribution profile. Targeted formulation accumulates more in breast and uterine tissues. ER-targeted formulation of antineoplastic agents could be potentially useful for treatment of ER positive tumors such as breast and uterus. Copyright © 2011 American Scientific Publishers All rights reserved.


Gupta M.,Drug Delivery Research Laboratory
Pharmaceutical development and technology | Year: 2013

Dermal delivery of fluconazole (FLZ) is still a major limitation due to problems relating to control drug release and achieving therapeutic efficacy. Recently, solid lipid nanoparticles (SLNs) were explored for their potential of topical delivery, possible skin compartments targeting and controlled release in the skin strata. The retention and accumulation of drug in skin is affected by composition of SLNs. Hence, the aim of this study was to develop FLZ nanoparticles consisted of various lipid cores in order to optimize the drug retention in skin. SLNs were prepared by solvent diffusion method and characterized for various in vitro and in vivo parameters. The results indicate that the SLNs composed of compritol 888 ATO (CA) have highest drug encapsulation efficiency (75.7 ± 4.94%) with lower particle size (178.9 ± 3.8 nm). The in vitro release and skin permeation data suggest that drug release followed sustained fashion over 24 h. The antifungal activity shows that SLNs made up of CA lipid could noticeably improve the dermal localization. In conclusion, CA lipid based SLNs are represents a promising carrier means for the topical treatment of skin fungal infection as an alternative to the systemic delivery of FLZ.

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