载紫杉醇的大黄酸偶联物纳米胶束的制备及初步评价  

Preparation and Preliminary Evaluation of Paclitaxel-loaded TPGS-CR Polymeric Micelles

作　　者：欧阳惠枝 邱梁桢 王夏英 徐伟[1] 王晓颖[1] OUYANG Hui-zhi;QIU Liang-zhen;WANG Xia-ying;XU Wei;WANG Xiao-ying(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福州350122

出　　处：《中国药学杂志》2020年第7期534-541,共8页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(81603301);福建省卫计委中青年骨干人才培养项目资助(2016-ZQN-69);福建省高校新世纪优秀人才支持计划资助(闽教科[2016]No.23);中医药公共卫生服务补助专项资助(财社[2017]66号)。

摘　　要：目的制备载紫杉醇的D-α-生育酚聚乙二醇1000琥珀酸酯(D-α-tocopheryl polyethylene glycol 1000 succinate,TPGS)修饰的羧甲基壳聚糖-大黄酸偶联物(PTX/TPGS-CR)纳米胶束,并对其进行初步评价。方法采用透析法,以载药量、包封率及粒径为指标,通过单因素考察优化PTX/TPGS-CR纳米胶束的制备工艺并进行验证。以溶血实验及血管刺激性实验初步考察PTX/TPGS-CR纳米胶束的安全性。四甲基偶氮唑盐微量酶反应比色法(MTT)法考察PTX/TPGS-CR纳米胶束对Hela细胞的毒性。通过激光扫描共聚焦显微镜定性和流式细胞仪定量考察Hela细胞对PTX/TPGS-CR纳米胶束的摄取情况。结果制备工艺优化后制得的PTX/TPGS-CR纳米胶束粒径为(197.3±4.4)nm,PDI为(0.131±0.021),电位为(-31.8±0.5)mV,载药量为(48.20±3.03)%,包封率为(87.26±4.91)%。溶血实验结果表明,其溶血率低于1.71%;血管静脉注射无明显刺激性。其对Hela细胞的杀伤作用具有浓度和时间依赖性,能被Hela细胞高效摄取。结论PTX/TPGS-CR纳米胶束载药量和包封率高,安全性好,其体外抗肿瘤活性稍优于Taxol?。OBJECTIVE To prepare paclitaxel loaded D-α-tocopheryl polyethylene glycol 1000 succinate(TPGS)-modified carboxymethyl chitosan-rhein polymeric micelles(PTX/TPGS-CR PMs)and preliminarily evaluate their performance.METHODS PTX/TPGS-CR PMs was prepared by dialysis method,and the preparation procedure of PTX/TPGS-CR PMs was optimized by single factor with the drug loading,encapsulation rate and particle size as the indicators,then the optimized preparation procedure was verified.The safety of PTX/TPGS-CR PMs was initially investigated by the hemolysis test and the vascular irritation test.The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was studied by MTT assay.Cell uptake experiments were performed by laser confocal microscopy and flow cytometry to investigate the uptake of PTX/TPGS-CR PMs by Hela cells.RESULTS The particle size and PDI of PTX/TPGS-CR PMs prepared by the optimized preparation were(197.3±4.4)nm and(0.131±0.021),respectively.The Zeta potential was(-31.8±0.5)mV.The drug loading and encapsulation efficiency were(48.20±3.03)%and(87.26±4.91)%,respectively.The hemolytic test results showed that the hemolysis rate was less than 1.71%.No obvious irritation was observed after intravenous injection.The cytotoxicity of PTX/TPGS-CR PMs in Hela cells was concentration-and time-dependent.Cell uptake experiments showed that PTX/TPGS-CR PMs could be efficiently uptake by Hela cells.CONCLUSION The PTX/TPGS-CR PMs has high drug loading and encapsulation efficiency,good safety.And they exhibite slightly better antitumor activity in vitro than Taxol?.

关 键 词：紫杉醇 大黄酸 羧甲基壳聚糖 D-α-生育酚聚乙二醇1000琥珀酸酯 聚合物胶束 抗肿瘤 

分 类 号：R944[医药卫生—药剂学]