包载雷帕霉素聚乳酸-聚乙醇酸纳米粒子的制备、表征及体外释放试验**☆

背景：新型可生物降解多聚物纳米控释载药制剂能显著改善药物穿透组织能力、再分布时程和滞留时间，可能克服载药基质对血管修复的负性影响，有望避免药物洗脱支架晚期支架内血栓。 目的：制备雷帕霉素-聚乳酸-聚乙醇酸纳米粒子（rapamycin poly(lactic-co-glycolic) acid nanoparticles, RPM-PLGA-NPs）并观察其表征及体外控释性能。 设计、时间及地点：单一样本实验于2003-03/09在中国医学科学院,中国协和医科大学,生物医学工程研究所生物医学材料重点实验室完成。 材料：聚乳酸-聚乙烯醇酸共聚物50∶50由美国Birmingham Polymers 公司提供。 方法：以可生物降解高分子材料聚乳酸-聚乙醇酸共聚物作载药基质，超声乳化-溶剂挥发法制备RPM-PLGA-NPs，采用双室扩散池行体外药物释放试验。 主要观察指标：测定平均载药量、平均包封率；激光光散射实验测定纳米粒子的粒径及分布；扫描电镜观察纳米粒子的表面形态；高效液相色谱法计算体外药物释放量、绘制累积释放曲线。 结果：成功制备了平均粒径为246.8 nm的RPM-PLGA-NPs，平均粒径246.8 nm，粒径分布集中在208~294 nm，呈窄分布；包封率大于77%,平均载药量为19.42%。体外释放近似于零级过程，至2周释放75％的药物。 结论：超声乳化-溶剂挥发法制备RPM-PLGA-NPs稳定可靠，包封效率高，载药量控制稳定，粒径小、范围窄，体外释放药物恒定、具有良好的控释效能。

Preparation, characterization and in vitro release of rapamycin-loaded poly(lactic-co-glycolic) acid nanoparticles

BACKGROUND: Novel biodegradable polymer nanometer controlled release carrier can significantly improve the penetration capacity, redistribution time course and residence time, it may overcome the negative influence of carrier matrix on the vascular repairing and is potential to avoid the late stent thrombosis in drug elution stent. OBJECTIVE: To prepare a biodegradable rapamycin poly(lactic-co-glycolic) acid nanoparticles (RPM-PLGA-NPs) and to assess its in vitro release characteristics. DESIGN, TIME AND SETTING: Single sample experiments were performed in the Key Laboratory of Biomedical Materials, Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College from March to September in 2003. MATERIALS: PLGA copolymer (50:50) was offered by Birmingham Polymers Company. METHODS: RPM-PLGA-NPs were prepared by an emulsification/solvent evaporation technique taking biodegradable PLGA as the carrier matrix, and in vitro release test was conducted utilizing double-chamber diffusion cells. MAIN OUTCOME MEASURES: The mean loading dose and encapsulation efficiency were determined; NP size distribution was assessed by submicro laser defractometer; The particle morphology was observed by scanning electron microscopy; The drug release in vitro was calculated using high performance liquid chromatography, and accumulative release curve was drawn. RESULTS: Biodegradable RPM-PLGA-NPs were constructed successfully. The mean diameter of RPM-PLGA-NPs was 246.8 nm with very narrow size distribution of 208-294 nm. RPM loaded in NPs were around 19.42%. Encapsulation efficiency of drug was over 77%. The in vitro release of RPM from NPs showed that 75% of the drug was sustained released over 2 weeks and controlled release in a linear pattern. CONCLUSION: RPM-PLGA-NPs are constructed successfully by an emulsification/solvent evaporation technique. The NPs show reliability and stability, high encapsulation efficiency, stable loading, small diameter, narrow size distribution, constant release in vitro, and good controlled drug delivery system.