具有应用前景的葡萄糖响应性药物载体

项目名称： 具有应用前景的葡萄糖响应性药物载体

项目编号： No.21274001

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 马如江

作者单位： 南开大学

项目金额： 60万元

中文摘要： 青年基金项目围绕含苯硼酸基团的聚合物，首次获得了在生理pH条件下具有葡萄糖响应性的嵌段共聚物胶束，实现了胰岛素的葡萄糖响应性控制释放。通过固体核磁等手段揭示了该胶束在pH 7.4具有葡萄糖响应性的机理。利用具有葡萄糖响应性内核和PEG/PNIPAM混合壳的复合胶束实现了葡萄糖浓度开关控制释放胰岛素。通过含苯硼酸基团的嵌段共聚物与糖基化聚合物复合，使所得胶束的葡萄糖敏感性大大提高。目前，已发表相关研究论文3篇（IF > 4），另有2篇论文在投稿或整理当中。 本项目是在青年基金项目基础上的扩展和深入，针对已有聚合物胶束，研究胰岛素载体的降血糖作用，负载化学降糖药物，研究其体外和体内释放行为。研究成不同结构的糖基化聚合物与含苯硼酸的聚合物的复合行为以及所得胶束的葡萄糖响应性。采用新的生物相容性聚合物替换原有材料中的非生物相容组分，改善载体的生物安全性。为葡萄糖响应性药物载体走向实用奠定基础。

中文关键词： 嵌段共聚物；葡萄糖响应性；复合胶束；药物控制释放；

英文摘要： In the Youth Science Foundation, we studied the glucose-responsiveness of phenylboronic acid-based block copolymer PEG-b-P(AA-co-AAPBA). It was firstly found that the self-assembled micelles could dissociate and release preloaded insulin in response to glucose at pH 7.4. The decrease of the pH value for the glucose-responsiveness was attributed to the coordination between carboxyl group and phenylboronic acid on the polymer chain based on Solid 11B NMR characterization of the micelles. Complexation between PEG-b-P(AA-co-AAPBA) and glycopolymer PAGA could substantially increase the sensitivity of the complex micelles to glucose. We also developed a reversible glucose-actuated nanocarrier with a P(Asp-co-AspAPBA) core and a mixed PEG/PNIPAM shell, which could repeatedly on-off release insulin in response to glucose. Until now, 3 papers have been published based on the youth science foundation, and 2 more papers are in review or writing. This project is the expansion and deepening of the previous Youth Science Foundation. In vivo study of antidiabetic effect of insulin-loaded PEG-b-P(AA-co-AAPBA) micelles will be carried out on rats by both oral and intravenous administration. Chemical antidiabetic drugs will also be loaded in PEG-b-P(AA-co-AAPBA) micelles for the treatment of diabetes by oral administration. Dif

英文关键词： block copolymer；glucose-responsiveness；complex micelle；controlled drug release；