Orally Delivered Polymeric nanoparticles of Lopinavir: Development and Statistical optimization, in vitro and ex vivo studies

Nanoparticles (NPs) have been extensively studied for oral drug delivery. NPs are taken up intact by M cells of peyer's patches of gut associated lymphoid tissue (GALT) followed by its systemic circulation thereby preventing first pass metabolism. This mechanism provides a chance to target antiretroviral drugs to lymphatic tissue. Lopinavir has poor oral bioavailability due to extensive first pass effect and limited intestinal uptake due to p-glycoprotein efflux. Main goal of study includes formulation and characterization of Lopinavir NPs for bioavailability enhancement and lymphatic targeting. PLGA NPs were prepared using Nanoprecipitation method. Formulation was optimized by 3(3) full factorial design using Particle size (PS) and entrapment efficiency (EE) as response parameters. Entrapment efficiency, Particle size and Zeta potential for optimized batch were found to be 90.36 +/- 0.426%, 169.9 +/- 0.231nm, -13.7 mV respectively. HPLC analysis was done using C 18 column (250 X 4.0 mm, 5 mu) at 210 nm. In vitro drug release studies showed the sustained release from NPs for 144h. Ex vivo studies through rat stomach and intestine confirmed that negligible amount of drug was released from NPs in the stomach. Lopinavir loaded NPs can be a suitable alternative to conventional tablet formulation.