We report a study of encapsulation and release from PLGA nanoparticles of a prodrug of zidovudine, an antiviral agent, obtained by its ester conjugation with a bile acid, the ursodeoxycholic acid. The nanoparticles were prepared by classical methods (nano-precipitation or emulsion/solvent evaporation) and purified by ultrafiltration or gel-filtration chromatography. The particle sizes and the size distribution have been determined by photon correlation spectroscopy and a SdFFF system, whereas particle morphology was detected by SEM. The stability of the free and encapsulated prodrug was evaluated in rat liver homogenates. The mean diameter of loaded nanoparticles was about 500 nm with a polidispersity relatively high, probably due to several aggregation states of nanoparticles with diameters around 100 nm. The loaded nanoparticles obtained by emulsion/solvent evaporation method appeared poorly able to control the release of the prodrug in a mixture of water and methanol (70:30 v/v), chosen to induce its solubilization. On the other hand, the nanoparticles obtained by nanoprecipitation (NP) were able to control the release of the prodrug, showing a burst effect of about 50% and a release of the remaining compound within five hours. The increase of prodrug amounts in the preparation phase of NP nanoparticles increased both the loading amount (ranging from 0.8 to 1.5 % w/w) and the release rate. The free prodrug was hydrolyzed in rat liver homogenates with an half life of 2.7 ± 0.14 min, whereas the loaded NP nanoparticles appeared able to significantly stabilize the prodrug in this physiologic fluid.
Polymeric nanoparticles for the sustained release of a prodrug of Zidovudine obtained by its conjugation with the ursodeoxycholic acid.
DALPIAZ, Alessandro;FOGAGNOLO, Marco;PERRONE, Daniela;CONTADO, Catia;PAVAN, Barbara;PAGANETTO, Guglielmo;
2012
Abstract
We report a study of encapsulation and release from PLGA nanoparticles of a prodrug of zidovudine, an antiviral agent, obtained by its ester conjugation with a bile acid, the ursodeoxycholic acid. The nanoparticles were prepared by classical methods (nano-precipitation or emulsion/solvent evaporation) and purified by ultrafiltration or gel-filtration chromatography. The particle sizes and the size distribution have been determined by photon correlation spectroscopy and a SdFFF system, whereas particle morphology was detected by SEM. The stability of the free and encapsulated prodrug was evaluated in rat liver homogenates. The mean diameter of loaded nanoparticles was about 500 nm with a polidispersity relatively high, probably due to several aggregation states of nanoparticles with diameters around 100 nm. The loaded nanoparticles obtained by emulsion/solvent evaporation method appeared poorly able to control the release of the prodrug in a mixture of water and methanol (70:30 v/v), chosen to induce its solubilization. On the other hand, the nanoparticles obtained by nanoprecipitation (NP) were able to control the release of the prodrug, showing a burst effect of about 50% and a release of the remaining compound within five hours. The increase of prodrug amounts in the preparation phase of NP nanoparticles increased both the loading amount (ranging from 0.8 to 1.5 % w/w) and the release rate. The free prodrug was hydrolyzed in rat liver homogenates with an half life of 2.7 ± 0.14 min, whereas the loaded NP nanoparticles appeared able to significantly stabilize the prodrug in this physiologic fluid.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
