重组人粒细胞集落刺激因子缓释微球的研究  

Study on PLAG Microspheres for Sustained Release of Recombinant Human Granulocyte Colony-stimulating Factor

作　　者：徐迪[1] 金拓[1] 吴飞[1] 袁伟恩[1] 

机构地区：[1]上海交通大学药学院上海,200240

出　　处：《现代生物医学进展》2007年第7期973-976,共4页Progress in Modern Biomedicine

摘　　要：目的:研究固体/油/水法制备重组人粒细胞集落刺激因子缓释微球,为开发其缓释剂型进行初步研究。方法:以聚乳酸-聚羟乙酸共聚物(PLGA)为载体材料:用固体/油/水法和水/油/水法制备载rhG-CSF缓释微球;考察粒径大小、外观、包封率等理化性质;用MicroBCA法考察微球的体外释药特性及影响因素;用SEC-HPLC和MTT比色法初步评价了微球制备工艺过程对rhG-CSF稳定性的影响。结果:两种方法制得的微球形态圆整、分散性良好,包封率均超过80%。固/油/水法制得的微球体外释放在2周内可超过90%,而水/油/水法制得的微球在相同的时间内仅释放30%。对于固/油/水法制备过程,SEC-HPLC法测定蛋白无明显聚集体出现,MTT法测定蛋白活性无明显损失。结论:实验证明了固/油/水法制备的PLGA微球可以实现2周以上的体外缓释。Objective： To prepare sustained released rhG-CSF loaded microspheres by S/O/W method, and to make preliminary research on developing a new strategy for delivering rhG-CSF in a sustained manner. Methods： rhG-CSF loaded microspheres were prepared with poly lactic-co-glycolic acid （PLGA） as carrier material by S/O/W and W/O/W methods separately. Physical and chemical characteristics of microspheres （mean diameter, morphology and drug enveloped rate） were evaluated; the release profiles of rhG-CSF fi：om PLGA microspheres made by S/O/W and W/O/W methods were compared, the in vitro release behavior and influencing factors of the microspheres were determined by MicroBCA method; and rhG-CSF stability during encapsulation was evaluated by SEC-HPLC; the bioactivities of rhG-CSF during the encapsulation process were determined by MTT method. Results： The 2 types of microspheres produced had similar good shape and dispersive quality as well as a drug entrapment efficiency of more than 80%. About 90% of encapsulated rhG-CSF prepared by S/O/W method was released out in a sustained manner fi：om PLGA microspheres within 2 weeks, but for rhG-CSF microspheres prepared by W/O/W method, only about 30% of rhG-CSF could be released out during the same period. Size exclusion chromatograms revealed that the structural integrity of released rhG-CSF fi：om microspheres prepared by S/O/W method was nearly intact, compared to that of native rhG- CSF; MTT result revealed that S/O/W method showed good protection to rhG-CSF during producing process. Conclusions： The research investigated a PLGA polymeric microparticulate formulation of rhG-CSF, and exhibited a sustained release profile over an extended period, without showing any significant alterations in structure. Protein encapsulated PLGA microspheres by S/O/W method will be a new promising strategy for delivering therapeutic protein drugs in a sustained manner.

关 键 词：粒细胞集落刺激因子 葡聚糖PLGA 微球 缓释 

分 类 号：R914.2[医药卫生—药物化学]