吉西他滨聚L-乳酸中空微球的制备及其酶解释放行为研究  

Preparation of gemcitabine poly(L-lactic acid) hollow microspheres and drug release behavior under enzymatic degradation

作　　者：王浩[1,2] 陈学思[2] 邓英杰[1] 

机构地区：[1]沈阳药科大学药学院 [2]中国科学院长春应用化学研究所高分子化学与物理国家重点实验室

出　　处：《中国药剂学杂志（网络版）》2011年第2期21-29,共9页Chinese Journal of Pharmaceutics：Online Edition

基　　金：国家自然科学基金项目(50373043);中国科学院科技创新基金项目(KJCX2-SW-H07)

摘　　要：目的制备包裹水溶性药物吉西他滨的中空结构可降解微球,考察药物在蛋白酶K作用下的释放行为。方法使用聚乙二醇-聚L-乳酸(PEG-PLLA)和聚L-乳酸(PLLA)两种材料,采用复乳法将吉西他滨包裹在内水相中,通过扫描电镜和激光散射粒径仪证实制备得到粒径大小相同的两种载药中空微球,并采用HPLC法对两种微球在蛋白酶K作用下的药物释放进行研究。结果采用PLLA和PEG-PLLA两种材料制得的微球内部均成蜂窝状结构。PEG-PLLA微球有药物突释,PLLA微球无药物突释;PEG嵌段的存在使得微球中包裹的药物释放更为完全。微球放置1个月后,在无蛋白酶K降解的情况下,PLLA微球的释药量少于40%,而PEG-PLLA微球的释药量为70%;有蛋白酶K降解的情况下,PLLA微球的释药量在50%左右,而PEG-PLLA微球中的释药量在70%以上。结论采用复乳法可以制备具有中空结构的聚L-乳酸微球,并使包裹在其中的药物呈现缓释特征,可以通过聚乙二醇嵌段来调节中空微球中药物的释放速率以及蛋白酶K对其降解程度。Objective To prepare gemcitabine loaded hollow microspheres using PEG-PLLA and PLLA by double emulsification method and to investigate the effect of enzyme degradation on drug release.Method By using double emulsification method,gemcitabine was entrapped in the inner aqueous phase,two kinds of drug loaded hollow microspheres with comparable particle size were obtained,the particle size was measured by dynamic light scattering and the morphology was observed using scanning electron microscope.Drug release from the two kinds of microspheres under enzymatic degradation was investigated using HPLC method.Results From microsphere’s cross section observation by ESEM,honeycomb structure was found in both kinds of microspheres.PEG segment in the PEG-PLLA microspheres led to burst release of the drug at the beginning and complete drug release in the end.In contrast,there was no burst release in PLLA microspheres.After about one month,when there was no proteinase K in the release media,less than 40% of the loaded drug was released from PLLA microspheres and about 70% from PEG-PLLA microspheres.When there was proteinase K in the release media,about 50% of the loaded drug was released from PLLA microspheres and more than 70% released from PEG-PLLA microspheres.Conclusion Poly(L-lactic acid) microspheres with hollow structure could be obtained by adopting double emulsion process and the microspheres could release drug in a sustained pattern.Drug release speed from the microspheres and degradation degree of the microspheres by proteinase K could be adjusted by polyethylene glycol block.

关 键 词：药剂学 中空微球 复乳法 吉西他滨 药物控制释放 蛋白酶K 

分 类 号：R94[医药卫生—药剂学]