超声引导瘤内注射型卡铂-PLGA缓释微球制备工艺优化研究

Technical Optimization of Preparation of carboplatin-loaded PLGA Microspheres for Intratumoral Injection Guided by Ultrasound

目的 探讨制备条件对微球粒径、表面形态和载药量的影响因素 ,确定制备超声引导瘤内注射型卡铂 -PLGA缓释微球的最佳工艺条件。方法 以O/O型乳化溶剂挥发法制备微球 ,采用单因素试验和拟水平均匀设计法优化制备工艺。结果 制备微球的最佳条件是卡铂晶体粒径 1～ 4μm ,CBP/PLGA投料比为 1∶7,PLGA浓度为 10 % ,内 /外相体积比为 1∶8,span -80浓度为 8% ,搅拌速度为 14 0 0r/min ,乳化和挥发时间分别是 15min和 4h ;此条件所制备微球呈规则球形、表面光滑 ,粒径 10 0～ 2 0 0 μm的微球产出率达到 65 .4% ,载药量为 11.6%。 结论 优化卡铂 -PLGA缓释微球的制备条件 。

Objective To discuss the effects of technical conditions on the morphology of surface, microparticle size and drug loading of the microspheres and to choose the best technical condition to prepare carboplatin-loaded PLGA microspheres for intratumoral injection guided by ultrasound. Methods Microspheres were prepared by an acetone/mineral oil emulsion and solvent evaporation method. Various factors related with the drug loading and microparticle size were studied. The uniform experimental design(U15) was chosen to optimize the technology of microspheres preparation. Results The best processing conditions for preparing microspheres were as following: the particle sizes of carboplatin was 1～4μm, the ratio of the carboplatin and PLGA was 1∶7, the PLGA concentration was 10%, the ratio of internal and external phases was 1:8, the emulsifier concentration in the external phase was 8%, stirring speed was 1400 rpm, the emulsion time was 15min, the solvent evaporaton time was 4 hr. The optimized microspheres of size 100～200μm were global, smooth-faced and with 65.4% of yield and 11.6% of the drug loading. Conclusion The carboplatin-loaded PLGA microspheres for intratumoral injection can be prepared by controlling preparative variables.