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Nanoparticles enhance per oral bioavailability of poorly available molecules: epigallocatechin gallate nanoparticles ameliorates cyclosporine induced nephrotoxicity in rats at three times lower dose than oral solution

Italia, J.L. and Datta, P. and Ankola, D.D. and Kumar, M.N.V.R. (2008) Nanoparticles enhance per oral bioavailability of poorly available molecules: epigallocatechin gallate nanoparticles ameliorates cyclosporine induced nephrotoxicity in rats at three times lower dose than oral solution. Journal of Biomedical Nanotechnology, 4 (3). pp. 304-312. ISSN 1550-7033

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Abstract

Epigallocatechin gallate (EGCG) has been proven to have great therapeutic potential in treatment and prophylaxis of various disorders, which are mediated by free radicals and oxidative stress. However, the poor biopharmaceutical properties and pharmacokinetics including poor stability in gastro-intestinal tract, low intestinal permeability and short plasma half life, have hindered its clinical development. In an attempt to overcome the above problems, EGCG was incorporated into PLGA nanoparticles. The nanoparticles were made following modified double emulsion method employing Didodecyldimethylammonium bromide (DMAB) as stabilizer. The particles were of similar to 130 nm size and polydispersity index of similar to 0.196 with encapsulation efficiency of 70% at 25% drug loading (w/w of polymer). The in vivo antioxidant efficacy of the EGCG nanoparticulate formulation was evaluated in a rat model of Cyclosporine (CyA)-induced chronic nephrotoxicity. Intraperitoneal (i.p.) administered EGCG solution was found to be efficacious in reducing the CyA-induced nephrotoxicity as evident form blood urea nitrogen, plasma creatinine and other parameters including plasma and renal malondialdehyde and glutathione levels, whereas orally administered EGCG solution was found to be ineffective. On the other hand, nanoparticulate formulation of EGCG administered per oral was found to be equally efficacious as i.p. administered EGCG solution in ameliorating CyA-induced renal damage at three times reduced dose. Together, these results suggest the potential of biodegradable nanoparticles in improving the therapeutic efficacy of EGCG.