Solid Lipid Nanoparticles for the sustained release of a prodrug of Zidovudine by its conjugation with ursodeoxycholic acid

Purpose: We report a study of encapsulation and release from solid lipid microparticles (SLMs) of a prodrug of zidovudine (AZT), an antiviral agent, obtained by its ester conjiugation with a bile acid, the ursodeoxycholic acid (UDCA). We have demonstrated that this prodrug is able to elude the active efflux systems expressed on physiological barriers. Results: The mean diameters of tristerain and stearic acid loaded microparticles were 7 and 14 micron, respectively. The shape of the SLMs was spherical and their prodrug loading was 0.57% (tristearin based) and 1.84% (stearic acid based). The tristearin SLMs were able to control the release of the prodrug, whereas the stearic acid SLMs induced a significant increase of the dissolution rate of the free prodrug obtained in the presence of Twwen 60. Conclusions. The developed SLMs were represent a good candidate for the local delivery of UDCA-AZT in the nose and its potential uptake in the brain