Fabrication via a nonaqueous nanoprecipitation method, characterization and in vitro biological behavior of N6-cyclopentyladenosine-loaded nanoparticles

A novel nonaqueous nanoprecipitation method was proposed to achieve the encapsulation of a small weight hydrophilic drug (N6-cyclopentyladenosine, CPA) in PLGA nanoparticles using a mixture of cottonseed oil and Tween-80 as nonsolvent phase. The nanoparticles were characterized in vitro as concerns size, morphology, drug loading, drug release, and drug stability in human blood. Human retinal pigment epithelium (HRPE) cells were employed to study intracellular accumulation of encapsulated or free CPA with and without unloaded particles, in the presence or absence of an equilibrative nucleoside transporter inhibitor. The particles displayed a mean size lower than 300 nm and a drug loading considerably higher than that found by conventional encapsulation methods. The suitable in vitro release properties permitted to obtain good drug stabilization in the blood. Studies on HRPE cells suggested that CPA can permeate their membrane by both diffusive- and transport-mediated mechanisms. The loaded and unloaded nanoparticles appeared able to increase the permeation rate of the diffusive mechanism, without interfering with the transporter. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4272-4284, 2009