DOI: 10.5176/2345-783X_PHARMA15.56
Authors: Longwei Sun and Gigi N. C. Chiu
Abstract:
In anti-HIV therapy, saquinavir mesylate (SQV) is administered together with ritonavir (RV). SQV exhibits low oral bioavailability due to its low solubility, P-glycoprotein (P-gp) mediated efflux and CYP3A metabolism. This study aims to increase the oral bioavailability of SQV through the development of multifunctional, pH-sensitive nanoparticles, which comprise the pH-sensitive Eudragit polymer and the P-gp inhibitor, Pluronic P85 (P85). These nanoparticles with diameters of ~270 nm displayed negative zeta potentials. Formulating SQV into Eudragit-P85 nanoparticles promoted drug permeation through the Caco-2 cell monolayers, and increased the oral AUC in mice 460{6e6090cdd558c53a8bc18225ef4499fead9160abd3419ad4f137e902b483c465} as compared to the oral drug suspension. Collectively, the multifunctional, pH-sensitive Eudragit-based nanoparticles could overcome the solubility and P-gp mediated drug efflux issues of SQV, and represent a promising approach in the delivery of protease inhibitors that suffer from similar bioavailability issues.
Keywords: Eudragit polymer; pH-sensitive; nanoparticles; saquinavir; oral bioavailability
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