艾塞那肽缓释微球的制备和体外释放的研究

Preparation of sustained-release microspheres containing exenatide and their in vitro release

目的制备载艾塞那肽的聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolicacid),PLGA]微球,并对其体外释药特性进行考察。方法以聚乳酸-羟基乙酸共聚物为载体,采用凝聚法(W/O/O)制备载艾塞那肽缓释注射微球,建立了高效液相色谱测定艾塞那肽含量的方法和微球中药物提取方法,考察微球粒径大小、外观、包封率、载药量等理化性质,并对微球体外释放特性进行了考察。结果微球球形较圆整,平均粒径为(51.2±1.97)μm,实际载药量为(4.50±0.13)%,包封率在(96.5±2.68)%,首日突释率为(13.19±1.39)%,28 d的体外累积释放率可达(88.6±0.73)%。结论以生物可降解的PLGA为载体,用W/O/O法制备的艾塞那肽微球工艺稳定可控,重现性好,可在体外缓释一个月,在糖尿病治疗中具有良好的应用前景。

Objective To prepare exenatide-loaded poly（lactic-co-glycolicacid）（PLGA） microspheres and to evaluate their release behavior in vitro.Methods Exenatide-loaded PLGA microspheres were prepared by W/O/O method using PLGA as vectors.An HPLC approach was established to determine the content and in vitro cumulative release.The physicochemical characteristics of microspheres,including the mean diameter,morphology,drug entrapment efficiency and loading efficiency,were evaluated.Results The prepared microspheres were well-shaped,with a mean diameter of（51.2±1.97） μm.The drug loading was（4.50±0.13）% and the encapsulation efficiency was（96.5±2.68）%.The first day burst release was（13.19±1.39）% and the in vitro 28-day-cumulative-release was（88.6±0.73）%.Conclusion The W/O/O method is stable,controllable,and repeatable for preparing exenatide-loaded microspheres using biodegradable polymers PLGA as the vector;the microspheres yield a one-month continuous release and have a bright future in treatment of diabetes mellitus.