载利福喷丁/聚乳酸-聚乙醇酸共聚物微球制备及体外释放

目的：制备可用于持续抑制脊柱结核术后病灶残留结核分枝杆菌的载利福喷丁／聚乳酸-聚乙醇酸共聚物[ Poly（ lactic-co-glycolic acid）， PLGA]微球，并研究其体外释放性能。方法通过乳化-溶剂挥发法制备载利福喷丁／PLGA微球，光学显微镜和扫描电镜观察微球形貌，激光粒度分布仪测定微球粒径及分布，紫外分光光度计测定微球载药量及包封率。检测利福喷丁抗结核分枝杆菌的最低抑菌浓度，并以pH＝7．4的PBS缓冲溶液为释放介质，紫外分光光度计检测载药微球体外释放特性。结果载利福喷丁／PLGA微球成球形状良好，表面光滑，分散性好，粒径分布均匀，平均粒径为25．49μm。载药量及包封率分别为21．37％±0．16％和74．79％±2．71％。体外释放实验显示在突释期内，利福喷丁释放量占载药微球中药物含量的37．08％±1．68％；在缓释期内载药微球释药速度减慢，第5周释放量仍超过利福喷丁抗结核分枝杆菌的最低抑菌浓度，35 d后体外累积释放量为80．67％±0．97％，仍高于利福喷丁抗结核分枝杆菌的最低抑菌浓度2μg／mL。结论 PLGA是一种理想的控缓释材料，所制备的载利福喷丁／PLGA微球具有良好的控释效果，是一种有效的抗结核缓释剂型。

Preparation and in vitro release of Rifapentine-loaded Poly(lactic-co-glycolic acid) microspheres

Objective To prepare Poly（ lactic-co-glycolic acid） （ PLGA） microspheres loaded with rifapentine to sustain-ably sterilize in the lesions of spinal tuberculosis.The physicochemical characteristics and in vitro release characteristics of rifapentine-loaded PLGA microspheres was studied in details.Methods Rifapentine-loaded PLGA microspheres was pre-pared by using single-emulsion solvent evaporation （ water-in-oil, O/W ） method, their morphology was observed by light microscope and scanning electron microscopy （SEM）.Rifapentine-loaded PLGA microspheres were analyzed about diameter with laser particle size analyzer, and their drug-loading rate and encapsulation rate were determined by ultraviolet spectropho-tometry.The minimal inhibitory concentration （MIC） of rifapentine against mycobacterium tuberculosis （H37Rv） was meas-ured.The microspheres were enclosed in the dialysis bag which suspended in PBS buffer solution （0.2 mol/L, pH7.4）, the release amount of rifapentine was detected by ultraviolet spectrophotometry and release curve was mapped.Results Rifapen-tine/PLGA microspheres presented sphericity, smooth surface, good dispersibility and uniform particle size.Their average particle size was 25.49 μm, the drug-loading rate and encapsulation rate was 21.37%±0.16% and 74.79%±2.71%, respectively.Almost 37.08%±1.68% of the rifampicin contained in the microspheres were released into PBS in the first 12 h.Although gradually reduced, the drug release in the fifth week was much higher than MIC, and rose to 80.67%± 0.97%35 d later, at that time the inhibitory concentration was more than the MIC of rifapentine against H37Rv 2 μg/mL. Conclusion PLGA is an ideal material for sustained-release preparations, and the rifapentine/PLGA microsphere was an effective antituberculosis dosage form, for its characteristics of well controlled-release effects.