紫杉醇PEGPLAVETPGS混合胶束递送系统的研究.docxVIP

紫杉醇 PEG-PLA/VE-TPGS 混合胶束递送系统的研究梁慧慧，范卓洋，陈昕怡，钱江辉，方晓玲，沙先谊*（教育部和全军智能化递药重点实验室，复旦大学药学院药剂教研室，上海市 201203）摘要：目的 构建载紫杉醇（PTX）的 PEG‐PLA/Vitamin E‐TPGS 混合胶束递药系统(PV‐PTX)，期望其逆转肿瘤多药耐药（MDR）效应。方法 采用薄膜水化法制备载 紫杉醇 PEG‐PLA/VE‐TPGS 混合胶束（PV‐PTX）。以粒径、包封率（ER%）、载药量（DL%）以及胶束溶液的稳定性为考察指标，综合考察了处方及工艺因素等对混 合胶束的影响。通过摄取和细胞毒实验评价 PV‐PTX 混合胶束在体外逆转肿瘤 MDR 的能力。结果 制得的混合胶束粒径在 17nm 左右，分布较窄，外形圆整， 大小均一，载药量在 24%左右，包封率约为 95%。PV‐PTX 混合胶束可以通过逆转 MDR 效应提高耐药肿瘤细胞对其的摄取量。结论 PV‐PTX 混合胶束是一种理想的 用于逆转肿瘤多药耐药性的给药系统。关键词：紫杉醇；多药耐药；Vitamin E-TPGSThe study of PTX-loaded PEG-PLA/VE-TPGS polymeric mixed micelledelivery systemLIANG Huihui, FAN Zhuoyang,CHEN Xinyi, QIAN Jianghui, FANG Xiaoling, SHA Xianyi (Key Laboratory of Smart Drug Delivery，Ministry of Education＆PLA， Department of Pharmaceutics，School of Pharmacy，Fudan University，Shanghai201203，China）ABSTRACT: OBJECTIVE To develop a PTX-loaded PEG-PLA/VE-TPGS mixed micelles delivery system (PV-PTX) ultimately, hopping that it could enhance the treatment of MDR tumors by the effects of overcoming MDR. METHOD The PTX-loaded PEG-PLA/VE-TPGS (PV-PTX) mixed micelle was prepared by film hydration method. The formulation and preparing process was evaluated with particle size, encapsulation ratio (ER%), drug-loading coefficient (DL%) and the percentage of PTX precipitated from the micelles, ultimately we obtained an optimized formulation method. We chose A549 and KBv as MDR cell model to evaluate themodulation of MDR by mixed micelles through the cellular uptake and cytotoxicity基金项目：国家自然科学基金作者简介：梁慧慧，女，硕士在读研究方向：药物新剂型与新技术*通讯作者：沙先谊，男，副教授，硕士生导师研究方向：药物新剂型与新技术Tel/Fax:(021 E‐mail：mailto:shaxy@fudan.edu.cnshaxy@fudan.edu.cnexperiments in vitro. RESULT The optimized mixed micelle showed a particle size of about 17nm with 24% for DL% and 95% for ER%. The results showed that the improved anticancer efficacy of PV-PTX micelles was associated with the enhanced cellular uptake by overcoming MDR. CONCLUSION we c