局部用雷帕霉素聚乳酸乙醇酸共聚物缓释微球的制备及释药研究

Preparation and in vitro release study of rapamycin in poly(lactic-co-glycolic )acid microsphere for topical administration

目的:介绍雷帕霉素(RAPA)聚乳酸乙醇酸共聚物(PLGA)缓释微球的制备方法,建立高效液相色谱法(HPLC)测定体系以检测微球中雷帕霉素含量,检测微球性状并进行体外释药实验。方法:以聚乳酸乙醇酸共聚物为载体,采用W/O/W乳剂-扩散溶剂挥发法制备雷帕霉素缓释微球,扫描电镜检测微球外观及微球粒径,HPLC检测微球载药量、包封率及体外释药量。结果:所制微球光滑圆整,大小均一,平均粒径:(121.18±27.83)μm,载药率:(14.39±1.32)%,包封率:(72.92±4.29)%,体外释放实验显示1～4天有突释,随后平稳释药至第10天累积释药率达80%。结论:采用制备工艺稳定,所制微球载药量及包封率均较高,形态完整,大小均一,体外释药较为平稳并且具有明显的缓释作用。

Objective To optimize the preparation technology of poly （lactide-co-glycolide） （PLGA） microspheres loaded with rapamycin （RAPA-PLGA-MS）, establish a HPLC method for content determination of rapamycin in microspheres and study powder particle characteristics and in vitro release characteristics of RAPA-PLGA-MS. Methods RAPA-PLGA-MS was prepared with PLGA as carriers by the water-in-oil-in-water （W/O/W） emulsion solvent evaporation method. Scanning electron miroscope （SEM） and HPLC were used to evaluate the micromeritic characteristics of RAPA-PLGA-MS, such as the particle size,loading efficiency, and entrapment efficiency and in vitro release characteristics. Results The prepared microspheres were spherical with smooth surfaces,with an average particle size of （121.18±27.83） μm. The loading and encapsulation efficiency were （14.39±1.32）% and （72.92±4.29）% respectively. The in vitro release curve of RAPA-PLGA-MS was up to 80% in 10 days. Conclusions Rapamycin poly （lactic-co-glycolic ）acid microspheres was successfully prepared and has obvious sustained release.