促黄体激素释放激素a(LHRHa)靶向鸦胆子油脂质体的制备及质量评价  

Preparation and quality evaluation of LHRHa-targeted Brucea javanica oil liposomes

作　　者：刘晓娟[1] 常淑芳[1] 孙江川[1] 叶红霞[1] 曾飚[1] 朱轶[1] 朱深银[2] 王驰[3] 

机构地区：[1]重庆医科大学附属第二医院妇产科,重庆400010 [2]重庆医科大学附属第一医院药剂科,重庆400016 [3]重庆医科大学药学院,重庆400016

出　　处：《解放军医学杂志》2013年第7期548-551,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(30801228);重庆市卫生局重点项目(2010-1-39);重庆市中医处重点项目(2010-1-6)~~

摘　　要：目的制备促黄体激素释放激素a(LHRHa)靶向鸦胆子油脂质体并评价其质量。方法采用薄膜分散法结合生物素-链霉亲和素桥接法制备LHRHa靶向鸦胆子油脂质体,正交设计优选处方,透射电镜下观察脂质体形态,采用Zetasizer Nano ZS分析仪测定脂质体粒径、Zeta电位,葡聚糖凝胶柱层析结合分光光度法测定包封率,通过离心加速实验及渗漏率考察脂质体稳定性,体外细胞实验鉴定脂质体靶向性。结果所得优化处方为磷脂与胆固醇比4:1,药物与脂质比3:10,DSPE-PEG-Biotin与卵磷脂质量比为3%,超声乳化时间为8min。按此处方制备的脂质体形态圆整,粒径为155.1±14.5nm,Zeta电位为–24.1±0.54mV,平均包封率达92.2%,对卵巢癌A2780/DDP细胞的亲和力约为普通脂质体的2.7倍。结论 LHRHa靶向鸦胆子油脂质体制备工艺可行,同时具有包封率高、稳定性及靶向性良好等优点。Objective To prepare luteinizing hormone-releasing hormone a（LHRHa） targeted Brucea javanica liposomes and evaluate its quality.Methods e LHRHa-targeted Brucea javanica liposome was prepared by thin layer dispersion together with biotinstreptavidin bridge method.The optimum formation was selected by means of orthogonal design of experiment.The morphology of liposome was observed with transmission electron microscope.Zetasizer Nano ZS analyzer was used to measure the particle size and zeta potential.e entrapment e ciency was determined by ultra-violet spectroscopy and column chromatography.Centrifugal acceleration experiment and determination of leak rate were performed to prove the liposome stability.e targeting ability of liposome was appraised by cell experiment in vitro.Results e formed optimum formula was as follows： the ratio of lecithin to cholesterol was 4：1,Brucea javanica oil：lipid was 3：10,DSPE-PEG（2000）-Biotin：lecithin content was 3%,ultrasonic-homogenized for 8 minutes.Liposomes were round in shape,the average diameter and zeta potential of liposome were 155.1±14.5mm and –（24.1±0.54） mV,respectively.The average entrapment e ciency was 92.2%.Binding capacity with the A2780/DDP cell line in the LHRHa-targeted liposomes was 2.7 times higher than that in the non-targeting liposomes.Conclusion e technique of preparing LHRHa-targeted Brucea javanica liposome is suitable,and high in entrapment e ciency,with good stability and targeting ability.

关 键 词：鸦胆子油脂质体 促黄体激素 卵巢肿瘤 

分 类 号：R943[医药卫生—药剂学]