LHRHa靶向紫杉醇脂质体的制备及体外抗肿瘤作用  

Preparation of LHRHa-Paclitaxel liposomes and its anti-tumor effect in vitro

作　　者：陈佳[1] 孙江川[1] 常淑芳[1] 朱轶[1] 朱深银[2] 

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

出　　处：《重庆医科大学学报》2012年第4期298-301,共4页Journal of Chongqing Medical University

基　　金：国家自然科学基金资助项目(编号:30801228);重庆市自然科学基金资助项目(编号:CSTC;2008BB5405);重庆市卫生局资助项目(编号:07-2-098;2011-1-39)

摘　　要：目的:制备促黄体激素释放激素类似物(Luteinizing hormone-releasing hormone analogues,LHRHa)靶向紫杉醇脂质体(Paclitaxel liposomes,PTX-Lipo),研究其在体外增强紫杉醇(Paclitaxel,PTX)对卵巢癌A2780/DDP细胞的抑制作用。方法:采用薄膜超声法制备PTX-Lipo与LHRHa靶向紫杉醇脂质体(LHRHa-Paclitaxel liposomes,LHRHa-PTX-Lipo),用透射电镜考察脂质体形态;高效液相色谱法测定2种PTX-Lipo的包封率;激光共聚焦法通过卵巢癌A2780/DDP细胞对4-氟-7-硝基-2,1,3-苯并氧杂恶二唑荧光素的摄取检测来反映细胞对NBD-Lipo与NBD-LHRHa-Lipo的摄取情况;MTT法及细胞克隆形成实验检测LHRHa-PTX-Lipo体外对卵巢癌细胞的生长抑制情况。结果:制备LHRHa-PTX-Lipo的平均粒径123.4 nm,包封率在90%以上;A2780/DDP细胞对NBD-LHRHa-Lipo组的荧光摄取明显高于NBD-Lipo组;LHRHa-PTX-Lipo对A2780/DDP细胞的生长及克隆形成抑制明显高于PTX组及PTX-Lipo组(P<0.05)。结论:采用薄膜超声法制备的LHRHa-PTX-Lipo可使药物在靶部位聚集,增强药物对卵巢癌细胞的抑制作用。Objective： To prepare LHRHa-Paclitaxel liposomes and to observe its inhibitory effect on ovarian cancer A2780/DDP cells in vitro.Methods：Paclitaxel liposomes（PTX-Lipo） and LHRHa-Paclitaxel liposomes（LHRHa-PTX-Lipo） were prepared by means of film ultrasound and their morphology was examined with transmission electron microscope.The encapsulation rates of PTX-Lipo and LHRHa-PTX-Lipo were quantified with high-performance liquid chromatography（HPLC）.The cellular intake of NBD-Lipo and LHRHa-NBD-Lipo was embodied through detecting the intake of NBD fluorescein by ovarian cancer A2780/DDP cells with laser confocal microscope.The inhibitory effect of LHRHa-PTX-Lipo on ovarian cancer cells in vitro was measured by MTT assay and colony-forming assay.Results：The mean diameter of LHRHa-PTX-Lipo particles was 123.4 nm with encapsulation rate being above 90%.The fluorescein intake of A2780/DDP cells was higher in NBD-LHRHa-Lipo group compared with that in NBD-Lipo group.The inhibitory effect of LHRHa-PTX-Lipo on the growth and clone formation of A2780/DDP cell was much more intense than that of PTX and PTX-Lipo（P0.05）.Conclusion： LHRHa-PTX-Lipo prepared by means of film ultrasound could aggregate drugs at targeted site thus increase the inhibitory effect of drugs on ovarian cancer cells in vitro.

关 键 词：脂质体 紫杉醇 靶向递送 促黄体激素释放激素类似物 生物素亲和素系统 卵巢癌 

分 类 号：R737.31[医药卫生—肿瘤]