Browsing by Author "Abhishesh K. Mehata"

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Bioadhesive micelles of D-α-tocopherol polyethylene glycol succinate 1000: Synergism of chitosan and transferrin in targeted drug delivery
(Elsevier B.V., 2017) Poornima Agrawal; Sonali; Rahul Pratap Singh; Gunjan Sharma; Abhishesh K. Mehata; Sanjay Singh; Chellapa V. Rajesh; Bajarangprasad L. Pandey; Biplob Koch; Madaswamy S. Muthu
The aim of this work was to prepare targeted bioadhesive D-α- tocopheryl glycol succinate 1000 (TPGS) micelles containing docetaxel (DTX) for brain targeted cancer therapy. Considering the unique bioadhesive feature of chitosan, herein, we have developed a synergistic transferrin receptor targeted bioadhesive micelles using TPGS conjugated chitosan (TPGS-chitosan), which target the overexpressed transferrin receptors of glioma cells for brain cancer therapy. The micelles were prepared by the solvent casting method and characterized for their particle size, polydispersity, zeta-potential, surface morphology, drug encapsulation efficiency, and in-vitro release. The IC50 values demonstrated transferrin receptor targeted TPGS-chitosan micelles could be 248 folds more effective than Docel™ after 24 h treatment with the C6 glioma cells. Further, time dependent bioadhesive cellular uptake study indicated that a synergistic effect was achieved with the chitosan and transferrin in targeted TPGS-chitosan micelles through the biodhesive property of chitosan as well as transferrin receptor mediated endocytosis. The in-vivo pharmacokinetic results demonstrated that relative bioavailability of non-targeted and targeted micelles were 2.89 and 4.08 times more effective than Docel™ after 48 h of treatments, respectively. © 2017 Elsevier B.V.
TPGS-chitosan cross-linked targeted nanoparticles for effective brain cancer therapy
(Elsevier Ltd, 2017) Poornima Agrawal; Rahul Pratap Singh; Sonali; Laksmi Kumari; Gunjan Sharma; Biplob Koch; Chellapa V. Rajesh; Abhishesh K. Mehata; Sanjay Singh; Bajarangprasad L. Pandey; Madaswamy S. Muthu
Brain cancer, up-regulated with transferrin receptor led to concept of transferrin receptor targeted anticancer therapeutics. Docetaxel loaded D-α-tocopherol polyethylene glycol 1000 succinate conjugated chitosan (TPGS-chitosan) nanoparticles were prepared with or without transferrin decoration. In vitro experiments using C6 glioma cells showed that docetaxel loaded chitosan nanoparticles, non-targeted and transferrin receptor targeted TPGS-chitosan nanoparticles have enhanced the cellular uptake and cytotoxicity. The IC50 values of non-targeted and transferrin receptor targeted nanoparticles from cytotoxic assay were found to be 27 and 148 folds, respectively higher than Docel™. In vivo pharmacokinetic study showed 3.23 and 4.10 folds enhancement in relative bioavailability of docetaxel for non-targeted and transferrin receptor targeted nanoparticles, respectively than Docel™. The results have demonstrated that transferrin receptor targeted nanoparticles could enhance the cellular internalization and cytotoxicity of docetaxel via transferrin receptor with improved pharmacokinetics for clinical applications. © 2017 Elsevier B.V.
Transition from passive to active targeting of oral insulin nanomedicines: Enhancement in bioavailability and glycemic control in diabetes
(Future Medicine Ltd., 2016) Dhansukh Kaklotar; Poornima Agrawal; Allabakshi Abdulla; Rahul P. Singh; Sonali; Abhishesh K. Mehata; Sanjay Singh; Brahmeshwar Mishra; Bajarangprasad L. Pandey; Anshuman Trigunayat; Madaswamy S. Muthu
Oral insulin nanomedicines are effective tools for therapy and management of both Type I and Type II diabetes. This review summarizes the various nanocarriers developed so far in the literature for oral delivery of insulin. It includes lipid-based (i.e., solid lipid nanoparticles and liposomes) and polymeric-based insulin nanomedicines (i.e., chitosan nanoparticles, alginate nanoparticles, dextran nanoparticles and nanoparticles of synthetic polymers) for sustained, controlled and targeted oral delivery of insulin. Mainly, goblet cell-targeting, vitamin B12 receptor-targeting, folate receptor-targeting and transferrin receptor-targeting aspects were focused. Currently, passive and active targeting approaches of oral insulin nanomedicines have improved the oral absorption of insulin and its bioavailability (up to 14%) that produced effective glycaemic control in in vivo models. These results indicate a promising future of oral insulin nanomedicines for the treatment of diabetes. © 2016 Future Medicine Ltd.