Exendin-4结构的稳定性及其微球制备

Stability of Exendin-4 Structure and Preparation of Exendin-4 Microspheres

目的分析影响Exendin-4二级结构稳定性的各种因素,并制备Exendin-4微球。方法利用远紫外圆二色光谱(Circular dichroism,CD)技术,分析pH值、温度、高速搅拌、油水界面对Exendin-4二级结构的影响及冰浴和蛋白质保护剂对其二级结构的保护作用。在此基础上,选用乳酸-羟基乙酸共聚物(PLGA)为成球材料,采用复乳法(W/O/W)制备Exendin-4微球,并对其理化性质进行评价。结果优化了实现Exendin-4二级结构稳定性的药剂学方法。制备的Exendin-4微球流动性良好,球形圆整,平均粒径为(25.3±3.2)μm,结构保持完好,微球的载药量约为1.0%,包封率为72.3%±2.4%,微球的释药曲线符合Higuchi释放模型,未发生明显的突释,具有良好的缓释效果。结论采取适当的药剂学方法,可以保证Exendin-4结构的稳定性并制备出理化性质合格的微球。

Objective To analyze various factors influencing the stability of secondary structure of Exendin-4 and prepare Exendin-4 microspheres.Methods The influence of pH value,temperature,high-speed homogenization and oil-water interface on the secondary structure of Exendin-4 as well as protective effect of ice bath and protein stabilizer on the structure were studied by far ultraviolet circular dichroism（CD）technique,based on which Exendin-4 microspheres were prepared with PLGA by W /O /W method and evaluated for physico-chemical property.Results The pharmaceutical method for stabilizing the secondary structure of Exendin-4 was optimized.The prepared Exendin-4 microspheres showed good fluidity,regular shape and intact structure,at a mean size of（25.3 ± 3.2）μm.The drug-loading and encapsulation efficiency of the microspheres were about 1.0% and 72.3% ± 2.4% re-spectively.The release curve of prepared microspheres was in a Higuchi mode,and no burst release was observed,indicating that the microspheres were controlled-released.Conclusion The stability of structure of Exendin-4 was kept by an appropriate pharmaceutical method,and Exendin-4 microspheres qualified in physico-chemical tests were prepared.