聚(ε-己内酯) -聚乙二醇-聚(ε-己内酯)两亲三嵌段共聚物蛋白大分子药物微球的研究  

Preparation and Drug Sustained Release Behavior of Poly(ε-caprolactone)/Poly(ethylene glycol)/Poly(ε-caprolactone) Amphiphilic Block Copolymeric Microspheres Containing Biological Macromolecule

作　　者：傅顺[1] 袁伟恩[1] 吴飞[1] 耿燕[1] 金拓[1] 

机构地区：[1]上海交通大学药学院,上海市200240

出　　处：《中国药房》2007年第31期2432-2434,共3页China Pharmacy

基　　金：国家自然科学基金资助项目(30472096)

摘　　要：目的:研究以聚(ε-己内酯) -聚乙二醇-聚(ε-己内酯) (PCE)制备蛋白大分子药物微球的方法及其与成品理化性质和释放动力学的关系。方法:采用复乳溶剂挥发法制备牛血清白蛋白(BSA) PCE微球,以扫描电镜观察微球的表面形态,以Mi-croBCA法测定微球载药量和包封率,以累积释放量考察微球体外释药特性。结果:微球外形圆整、表面光滑。不同分子量PCE微球载药量和包封率相近,但体外释药特性显著不同,释放机制为扩散-降解,其中PCE4000因扩散作用释出的蛋白量明显低于其它分子量所制微球。微球体外释药规律符合扩散-溶蚀(Q=k1t1/2+k2t+k3t2+k4t3)(r=0.997)方程。结论:以PCE制备蛋白大分子药物微球具有良好的缓释效果,突释小,释放完全。OBJECTIVE： To characterize morphology and drug release kinetics of protein - loaded poly（ε - caprolactone）/ poly（ethylene glycol）/poly（ε-caprolactone） amphiphilic block copolymeric （PCE） microspheres, and elucidate the mechanistic details regarding protein release. METHODS： BSA- loaded PCE microspheres were prepared using a water- in- oil- in- water, followed by solvent evaporation. Morphology of the polymer microspheres was observed using scanning electron microscopy. Protein loading capacity and encapsulation efficiency were determined by extracting the proteins from the microspheres and measured using MicroBCA method. Protein release kinetics was characterized by cumulative release against the date of release incubation. RESULTS： The protein - loaded PCE microspheres were spherical and possess smooth surface under SEM. Protein loading capacity and encapsulation efficiency in the microspheres were independent of PCE molecular weight. However, the kinetic features of the protein release varied significantly with PCE molecular weight, suggesting a diffusion- degradation combined release mechanism. For the microspheres made of larger molecular weight PCE 4000, the portion of protein release attributed to diffusion from the polymer matrix was remarkably less than that from microspheres of small molecular weight PCE. In vitro release profile can be simulated using a diffusion- degradation model（ Q = k1t 1/2＋ k2t ＋ k3t^2＋ k4t^3） （r = 0.997） , CONCLUSION： PCE microsphere formulation can offer sustainedrelease of proteins with initial burst and incomplete release reduced to acceptable level.

关 键 词：聚(ε-己内酯)-聚乙二醇-聚(ε-己内酯) 微球 体外释药 缓释 

分 类 号：R944.9[医药卫生—药剂学] R977.6[医药卫生—药学]