alexa Optimized PLGA nanoparticle platform for orally dosed trans-resveratrol with enhanced bioavailability potential.
Biomedical Sciences

Biomedical Sciences

Journal of Biomolecular Research & Therapeutics

Author(s): Singh G, Pai RS

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Abstract BACKGROUND: Trans-resveratrol (t-RVT) is a potent antioxidant. The drug suffers enterohepatic recirculation and extensive first-pass metabolism by CYP3A4 in liver, resulting in very low bioavailability (almost zero). OBJECTIVE: The current studies entail a novel formulation approach to develop systematically optimized (OPT) nanoparticles (NPs) to enhance the oral bioavailability potential using poly (dl-lactide-co-glycolide) (PLGA) of t-RVT and overcome enterohepatic recirculation. METHODS: T-RVT-loaded PLGA NPs were prepared by nanoprecipitation method. Delineating the NP regions, the amounts of polymer and emulsifier were selected as the critical factors for systematically formulating the OPT NPs employing 3(2) central composite design. The pharmacokinetics, in vivo biodistribution and in situ single-pass intestinal perfusion (SPIP) studies of OPT formulation were investigated in male Wistar rats. RESULTS: Augmentation in the values of Ka (7.17-fold) and AUC0 - ∞ (10.6-fold) indicated significant enhancement in the rate and extent of bioavailability by the OPT formulation compared to pure drug and marketed product. OPT formulation showed a 2.78-fold rise in the values of t-RVT concentrations in liver. In situ SPIP studies ascribed the significant enhancement in absorptivity and permeability parameters of OPT NPs to transport through the Peyer's patches. Successful establishment of in vitro/in vivo correlation substantiated the judicious choice of the in vitro dissolution milieu for simulating the in vivo conditions. CONCLUSION: The studies, therefore, could provide another useful tool for successful development of t-RVT NPs and an in vivo approach to designate nanoparticulate system of t-RVT with distinctly improved bioavailability and to overcome enterohepatic recirculation. This article was published in Expert Opin Drug Deliv and referenced in Journal of Biomolecular Research & Therapeutics

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