基于多药协同作用和逆转肿瘤耐药性的纳米药物载体的设计和构筑

项目名称： 基于多药协同作用和逆转肿瘤耐药性的纳米药物载体的设计和构筑

项目编号： No.51473141

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 一般工业技术

项目作者： 张雪飞

作者单位： 湘潭大学

项目金额： 85万元

中文摘要： 本项目提出制备一种以丙交酯（LA），己内酯（CL）嵌段聚合物为主链，在其侧链上引入不同官能团，在此基础上将多种化疗药物通过化学键合的方法，键接到聚合物的不同官能团上，得到载有多种化疗药物的两亲性高分子键合药。同时通过对两亲性高分子键合药进行自组装，把亲油性的P-糖蛋白抑制剂包载在纳米胶束的内腔里，最终制备一种具有逆转肿瘤耐药性和多药协同作用的纳米药物载体体系。由于是物理包裹在胶束的内腔，P-糖蛋白抑制剂比化疗药物的释放就会更早和更快，这样可以实现P-糖蛋白抑制剂和化疗药物同时被输送到肿瘤组织和他们的有序先后释放。通过对制备的纳米载药体系的自组装行为，模拟人体生理环境下的体外药物释放行为进行研究，以及体外细胞和体内细胞实验，对这载药体系的细胞毒性行为，协同效应和抑制耐药性效果进行研究，探讨其作用机理与影响因素，为进一步设计与制备新型纳米药物载体和给药体系提供依据和指导。

中文关键词： 药物载体；自组装；纳米载体；药物控制释放；生物医用高分子

英文摘要： This project was proposed to prepare a kind of amphiphilic block polymer, which was made up of lactide (LA), caprolactone (CL) as the main chain and different functional groups in its side chain. multiple chemotherapeutic drugs were conjugated to the different functional groups of the polymer and the amphiphilic polymer-drug conjugate was obtained carrying a variety of chemotherapeutic drugs. Hydrophobic P-glycoprotein (P-gp) inhibitor was encapsulated into the micelles formed by the self-assembly of the amphiphilic polymer-drug conjugate, eventually, a kind of nanomedicine carrier system was Prepared with reversing multidrug resistance(MDR)of tumor and multiple drugs synergistic effects. owing to entrapped into the micelles physically, P-gp inhibitor could be released earlier and faster than the chemotherapeutic drugs, and drugs could be simultaneously delivered to tumor region and Sequentially release. The self-assembly, drug release assessment in vitro should be studied. The cytotoxicity will also be conducted in vitro and vivo. Meanwhile, synergistic effects and reverse the MDR effect should be studied, which should contribute to discover the mechanism and the influencing factors. These insights should provide more basis and guidance toward the design and development of novel nanomedicine carriers and dosage system for anticancer application.

英文关键词： drug carrier;self-assembly;nanocarrier;controlled drug release;biomedical polymer