Development and characterization of PLGA nanoparticles as delivery systems of a prodrug of zidovudine obtained by its conjugation with ursodeoxycholic acid

The main purpose of this study was to investigate the effect of the Pluronic F68 coating on the loading, release and stability of PLGA nanoparticles embedded with a prodrug of zidovudine, an anti HIV agent, obtained by its conjugation with ursodeoxycholic acid. The mean diameter of the nanoparticles prepared by nanoprecipitation or emulsion/solvent evaporation methods was determined using both photon correlation spectroscopy and sedimentation field–flow fractionation (SdFFF) and resulted about 600 nm with a relatively high polidispersity. The nanoparticles obtained by emulsion/solvent evaporation method were not able to control the prodrug release while the nanoparticles obtained by nanoprecipitation were able to control the release of the prodrug, showing a burst release of about 50%. The presence of the Pluronic coating did not substantially modify the kinetics of the drug release nor the extent of the burst effect which was instead only influenced by the preparation parameters. The prodrug incorporated in the nanoparticles was more stable in the rat liver homogenates than the free prodrug and no influence of the Pluronic coating was observed. Considering the different potential applications of nanoparticles coated and uncoated with Pluronic, both of these nanoparticle systems could be useful in the therapies against HIV