Preparation, Characterization and in vitro/in vivo Evaluation of Lovastatin-Loaded PLGA Microspheres by Local Administration for Femoral Head Necrosis

BACKGROUND: The present work is an effort to develop a novel locally injection LVTT-loaded PLGA microspheres (LVTT-PLGA-MS) on the treatment of rabbits with femoral head necrosis (FHN). METHODS: LVTT-loaded PLGA microspheres (LVTT-PLGA MS) were prepared by an emulsion-solvent evaporation method. The physicochemical properties of LVTT-PLGA-MS were investigated to ensure that they have good qualities and are suitable for local delivery. In vitro drug release behavior of MS was also studied compared with free LVTT. In vivo, we also studied the pharmacokinetics and pharmacodynamics of MS in rabbits with the optimized formulation. RESULTS: In this study, we used the emulsion-solvent evaporation method to prepare LVTT-PLGA MS. Scanning electron microscopy demonstrated that the LVTT-PLGA MS were regular, round in shape and relatively unified size distributions were selected. The mean PS was 12.3±2.1 µm. The drug-loading rate (27.6% ± 2.9%) was calculated for three batches of MS. The thermogram of LVTT-PLGA MS showed an endothermic peak at 98.3°C, revealing that LVTT existed in MS in an uncrystallized rather than a crystallized form. In the release study, LVTT-PLGA MS is observed linear prolonging drug release rates for more than 21 days without initial burst release. The pharmacodynamic results confirmed that the LVTT-PLGA MS had a good and lasting improvement effect against femoral head necrosis. CONCLUSION: Our results demonstrated that LVTT-PLGA MS has the potential for being a local delivery system.