高分子聚合物包裹胰岛素微球的制备及其体外质量评价

目的：采用水包油包张复乳法制备聚乙烯醇-聚乳酸羟基乙酸（PVA-g-PLGA）胰岛素微球，建立测定胰岛素PVA-g-PLGA微球药物含量的高效液相色谱法，通过考察微球的外观、粒径、载药率和包封率对微球的质量进行评价，通过比较PLGA和PVA-g-PLGA微球的体外降解pH变化来初步判断PVA-g-PLGA是否具有蛋白保护能力。 方法：利用扫描电子显微镜观察胰岛素微球的表面形貌，使用激光粒度仪测定微球的粒径分布，用高效液相色谱仪测定微球的载药率和包封率。 结果：所制备的胰岛素PVA-g-PLGA微球粒径均一、光滑、圆润，微球之间没有粘连，微球粒径在1800~4000 nm之间，分布相对集中；微球含量为170.8 μg·mg^-1，载药率为1.53%，包封率为56.51%，96 h的累积释放率为42.67%；随着时间的延长，PLGA微球体外降解的pH明显低于PVA-g-PLGA微球。 结论：采用复乳法制备的微球外观光滑、圆润，微球之间无粘连，粒径均一；所建立的HPLC含量测定方法符合方法验证基本要求；PVA-g-PLGA微球具有一定的蛋白保护能力。

Objective: To prepare insulin PVA-g-PLGA microspheres by water/oil/water (w/o/w) emulsion method,to establish an HPLC method to detect microsphere drug content,to evaluate the quality of the microspheres by investigating the appearance,particle size and drug loaded percentage of microspheres,and to compare the PLGA and PVA-g-PLGA microspheres in vitro degradation of pH changes,so as to preliminariy judge whether PVA-g-PLGA has protein protection ability. Methods: Scanning electron microscope was adopted to observe the surface morphology of insulin microspheres;laser particle analyzer was used for the determination of particle size distribution of microspheres;microspheres drug loaded percentage and encapsulation efficiency were measured by high performance liquid chromatograph. Results: The insulin PVA-g-PLGA microsphere prepared in this study were uniform,smooth,and mellow;there was no adhesion between microspheres,the microsphere particle size was relatively concentrated between 1800-4000 nm;microsphere's drug content was 170.8 μg·mg^-1,drug content rate was 1.53%,encapsulation efficiency was 56.51% and the cumulative release rate was 42.67% at 96 h;with the extension of time,the pH in vitro degradation of the PLGA microspheres was remarkably lower than that of PVA-g-PLGA microspheres. Conclusion: The microspheres prepared by w/o/w emulsion method are smooth,rounded,uniform,and without adhesion between microspheres.The established HPLC method meets the basic requirements of the methodology validation.PVA-g-PLGA microspheres have certain protective effects on proteins.

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