艾塞那肽长效缓释微球的制备及体内药效学研究.doc

艾塞那肽长效缓释微球的制备及体内药效学研究 刘斌1,2，董庆光1，王梦舒1，李纯1，孔维1,2，陈妍1* (1.吉林大学生命科学学院，长春 130012； 2.吉林大学超分子结构与材料国家重点实验室，长春 130012.) 摘要：目的 制备艾塞那肽长效缓释微球，并考察其理化性质、体外释放特性及体内药效学。方法 采用复乳－溶剂挥发法（W/O/W）制备包裹艾塞那肽的聚乳酸－羟基乙酸嵌段共聚物（PLGA）微球；考察微球的粒径分布、表面形态、载药量和包封率； 用micro－BCA试剂盒测定微球的体外释放速率；考察了微球在糖尿病模型小鼠体内的降血糖作用。结果 微球外观光滑圆整，分散性好，艾塞那肽载药量为3％，包封率为75％；微球40d之内体外累积释放达到88％，其体外释放曲线近似零级释放模式；体内药效学实验结果显示，40d内微球组小鼠与模型对照组小鼠血糖相比具有显著性差异（P0.05）。结论 采用复乳－溶剂挥发法成功制备了可以缓释40d的艾塞那肽长效微球，且40d之内在糖尿病小鼠体内具有明显的降血糖作用。 关键词：艾塞那肽；聚乳酸－羟基乙酸嵌段共聚物；微球；血糖 中图文类号： 文献标识码： 文章编号： Preparation of Long-acting Release Microspheres of Exenatide and Studies on Their in vivo Pharmacodynamics LIU Bin1,2，DONG Qing-Guang，WANG Meng-Shu，LI Chun，KONG Wei，CHEN Yan* （1. College of Life Science, Jilin University, Changchun 130012, China； 2. State Key Laboratory Supramolecular Structure Materials, Jilin University, Changchun 130012.,China.） ABSTRACT: OBJECTIVE To prapere Exenatide loaded long-acting release microspheres, and to evaluate their physical and chemical characteristics、in vitro release behavior as well as in vivo pharmacodynamics. METHOD Exenatide loaded PLGA microspheres were prepared by double emulsion(W/O/W)method. The mean diameter、morphology、drug loading and encapsulation efficiency were evaluated. The micro-BCA protein assay was used for the in vitro release behavior. The effect of reducing plasma glucose were evaluated on the diabetes mice. RESULTS The microspheres possessed smooth and round appearance as well as good dispersive quality. The drug loading and encapsulation efficiency was 3% and 75%. The in vitro accumulated release within 40d reached up to 88%, and the release profile is consistent with zero-class release model. The results of in vivo pharmacodynamics indicated that the plasma glucose of mice injected with Exenatide microspheres was different significantly from the plasma glucose of the diabetes model mice within 40d (P0.05). CONCLUSION The Exenatide loaded long-acting release microspheres which could yield