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

Context. Zidovudine (AZT) is employed against AIDS and hepatitis; its use is limited by active efflux transporters (AET) that induce multi-drug resistance for intracellular therapies and hamper AZT to reach the brain. Ursodeoxycholic acid conjugation with AZT (prodrug UDCA-AZT) allows to elude the AET systems. Objective. To investigate the effect of the Pluronic F68 coating on the loading, release and stability of PLGA nanoparticles (NP) embedded with UDCA-AZT. Materials and Methods. The mean diameter of the NP prepared by nanoprecipitation or emulsion/solvent evaporation methods was determined using both photon correlation spectroscopy and sedimentation field–flow fractionation (SdFFF); particle morphology was detected by SEM. The stability of the free and encapsulated UDCA-AZT was evaluated in rat liver homogenates, by HPLC analysis. Results and discussion. The mean diameter of the NP resulted about 600 nm with a relatively high polidispersity. The nanoparticles obtained by emulsion/solvent evaporation were not able to control the prodrug release, differently from nanoparticles obtained by nanoprecipitation. The presence of the Pluronic coating did not substantially modify the kinetics of the drug release, nor the extent of the burst effect that were instead only influenced by the preparation parameters. UDCA-AZT 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. Conclusions. Considering the different potential applications of nanoparticles coated and uncoated with Pluronic (brain and macrophage targeting, respectively), both of these nanoparticle systems could be useful in the therapies against HIV.