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通过硼酸-二醇络合作用制备葡萄糖响应性聚合物胶束用于中性 pH 下胰岛素的传递

Glucose-Responsive Polymeric Micelles via Boronic Acid-Diol Complexation for Insulin Delivery at Neutral pH.

机构信息

Institute for Technical and Macromolecular Chemistry , University of Hamburg , Bundesstrasse 45 , D-20146 Hamburg , Germany.

Institute for Chemical Technology and Polymer Chemistry , Karlsruhe Institute of Technology (KIT) , Engesser Strasse. 18 , D-76131 Karlsruhe , Germany.

出版信息

Biomacromolecules. 2019 Feb 11;20(2):871-881. doi: 10.1021/acs.biomac.8b01508. Epub 2019 Jan 22.

DOI:10.1021/acs.biomac.8b01508
PMID:30608155
Abstract

In the present study, glucose-responsive polymeric complex micelles based on the complexation of phenylboronic-acid-based (PBA-based) block copolymer and diol-functionalized polymers are reported. The phenylboronic-acid- and diol-based block copolymers were successfully synthesized in only two reaction steps using reversible addition-fragmentation chain-transfer (RAFT) polymerization and postpolymerization modification of the obtained poly[( N-acryloylmorpholine- block-( N-acryloylmorpholine- co-pentafluorophenyl acrylate)], poly[(AMP- b-(AMP- co-PFPA)], reactive block copolymer. The self-assembly of the complex micelles was investigated under neutral conditions using dynamic light scattering (DLS) and transmission electron microscopy (TEM). The interaction of the PBA block copolymer and diol-containing polymer via boronate ester bond was investigated by H NMR and UV-vis spectroscopy. The complex micelles enhanced the glucose responsiveness under physiological conditions compared to simple PBA micelles. Furthermore, the successful glucose-triggered release of FITC-insulin from the polymeric micelles was investigated.

摘要

在本研究中,报告了基于苯硼酸基(PBA 基)嵌段共聚物与二醇功能化聚合物络合的葡萄糖响应性聚合物复合胶束。通过可逆加成-断裂链转移(RAFT)聚合和所得聚[(N-丙烯酰吗啉-嵌段-(N-丙烯酰吗啉-co-五氟苯丙烯酸酯)]、聚[(AMP-b-(AMP-co-PFPA)]、反应性嵌段共聚物的聚合后修饰,成功地在仅两步反应中合成了苯硼酸和二醇基嵌段共聚物。使用动态光散射(DLS)和透射电子显微镜(TEM)在中性条件下研究了复合胶束的自组装。通过 1H NMR 和紫外-可见光谱研究了 PBA 嵌段共聚物与含二醇聚合物之间通过硼酸酯键的相互作用。与简单的 PBA 胶束相比,复合胶束在生理条件下增强了葡萄糖响应性。此外,还研究了 FITC-胰岛素从聚合物胶束中的葡萄糖触发释放。

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