胆甾醇基γ-聚谷氨酸载紫杉醇自组装纳米胶束的制备与性能  

Preparation and properties of paclitaxel-loaded self-assembling nano-micelles of cholesterol-bearing γ-Polyglutamic acid

作　　者：胡凡[1] 肖港 王育川 姚俊[2] 曹新[2] HU Fan;XlAO Gang;WANG Yuchuan;YAO Jun;CAO Xin(Analysis and Test Center of Nanjing Medical University, Nanjing 211166, P.R. China;School of Basic Medical Science, Department of Biotechnology, Nanjing Medical University, Nanjing 211166, P.R. China)

机构地区：[1]南京医科大学分析测试中心,南京211166 [2]南京医科大学基础医学院生物技术系,南京211166

出　　处：《生物医学工程学杂志》2018年第3期403-408,共6页Journal of Biomedical Engineering

基　　金：国家自然科学基金青年基金项目(51403103);江苏省大学生创新创业训练计划项目(201710312065X)

摘　　要：本文采用两亲性胆甾醇基γ-聚谷氨酸纳米胶束(γ-PGA-graft-CH NMs)负载紫杉醇(PTX),考察了该胶束体系的载药性能与体内外特性。研究结果表明,γ-PGA-graft-CH NMs对PTX体现了良好的负载性能,最佳药载比为1/10,载药量达26.9%±0.8%,包封率88.6%±1.7%,对应载药纳米胶束(PTX/NMs)的粒径为(343.5±7.3)nm;体外释药结果显示,PTX/NMs能延缓PTX的释放,并具有p H敏感的释药特性和较低的细胞毒性;药代动力学研究表明,PTX/NMs在小鼠体内的消除半衰期(t1/2β)、血药浓度–时间曲线下面积(AUC)均明显大于PTX/聚氧乙烯蓖麻油注射剂(PTX/PCO),并具有较低的清除率(CL);PTX/NMs在肝脏和瘤体分布高于PTX/PCO,且对荷瘤小鼠具有良好的抑瘤效果。本研究针对将γ-PGA-graft-CH NMs用于抗肿瘤给药系统奠定了一定的基础。Paclitaxel（PTX）-loaded self-assembling nano-micelles（PTX/NMs） were prepared based on amphiphilic cholesterol-bearing γ-polyglutamic acid（γ-PGA-graft-CH）. The properties of PTX/NMs in vitro and in vivo were investigated. The results indicated that PTX could be entrapped in γ-PGA-graft-CH NMs. PTX/NMs was characterized with a size of（343.5 ± 7.3） nm, drug loading content of 26.9% ± 0.8% and entrapment efficiency of 88.6% ±1.7% at the optimized drug/carrier ratio of 1/10, and showed a p H-sensitive sustainable drug-release and less cytotoxicity in vitro. In vivo release and the pharmacokinetics study in mice showed that the elimination half-life（t1/2β） and area under curve（AUC） of PTX/NMs were significantly higher than those of PTX/polyoxyethylene castor oil（PTX/PCO）, and less clearance（CL） of PTX/NMs was also observed. PTX/NMs were distributed higher in liver and tumor than PTX/PCO, and showed a good tumor-inhibiting activity in tumor-bearing mice. This study would lay a foundation on the potential application of γ-PGA-graft-CH NMs were the antitumor drug-delivery.

关 键 词：Γ-聚谷氨酸 纳米胶束 药物载体 药代动力学 抑瘤试验 

分 类 号：R943[医药卫生—药剂学]