Fabrication Via a Nonaqueous Nanoprecipitation Method,Characterization and In Vitro Biological Behavior ofN6-Cyclopentyladenosine-Loaded Nanoparticles

A novel nonaqueous nanoprecipitation method was proposed to achieve theencapsulation of a small weight hydrophilic drug (N6-cyclopentyladenosine, CPA) inPLGA nanoparticles using a mixture of cottonseed oil and Tween-80 as nonsolventphase. The nanoparticles were characterized in vitro as concerns size, morphology, drugloading, drug release, and drug stability in human blood. Human retinal pigmentepithelium (HRPE) cells were employed to study intracellular accumulation of encapsulatedor free CPA with and without unloaded particles, in the presence or absence of anequilibrative nucleoside transporter inhibitor. The particles displayed a mean size lowerthan 300 nm and a drug loading considerably higher than that found by conventionalencapsulation methods. The suitable in vitro release properties permitted to obtain gooddrug stabilization in the blood. Studies on HRPE cells suggested that CPA can permeatetheir membrane by both diffusive- and transport-mediated mechanisms. The loaded andunloaded nanoparticles appeared able to increase the permeation rate of the diffusivemechanism, without interfering with the transporter.