张建华^1,2，杨聚敏 ¹，姚 丹 ¹，董岸杰 ¹

AuthorsHTML:张建华^1,2，杨聚敏 ¹，姚 丹 ¹，董岸杰 ¹

AuthorsListE:Zhang Jianhua^{1, 2}，Yang Jumin¹，Yao Dan¹，Dong Anjie¹
AuthorsHTMLE:Zhang Jianhua^{1, 2}，Yang Jumin¹，Yao Dan¹，Dong Anjie¹
Unit:1. 天津大学化工学院，天津 300072； 2. 天津大学天津市膜科学与海水淡化技术重点实验室，天津 300072

Unit_EngLish:1. School of Chemical Engineering and Technology，Tianjin University，Tianjin 300072，China；
2. Tianjin Key Laboratory of Membrane Science and Desalination Technology，Tianjin University，Tianjin 300072，China
Abstract_Chinese:开发胰岛素凝胶给药系统对于提高糖尿病的治疗效果具有重要意义，但是由于胰岛素具有独特的理化属性和给药方式，单一的高分子凝胶一般难以满足其高效大量负载、精确长效控释的要求．本研究利用苯基硼酸(PBA)的葡萄糖敏感特性，制备苯基硼酸表面改性的聚乳酸-co-羟基乙酸(PLGA)多孔微球(PBA-PLGA SM)，再将聚乙烯醇(PVA)溶液与负载胰岛素的微球进行共混，通过形成动态硼酯键制备葡萄糖敏感的多孔微球/聚合物(PBA-PLGA SM/PVA)复合凝胶，创造性地将胰岛素负载、刺激响应、控制释放3个关键职能，划分到该复合水凝胶的不同组成单元上，充分发挥PBA 功能基团、PLGA多孔微球、高分子聚合物水凝胶的各自功能和协同效应，设计了一种具有葡萄糖敏感特性的胰岛素水凝胶给药系统．重点研究了该复合凝胶的凝胶特性、葡萄糖敏感性、体外降解性及细胞毒性等．结果说明这一复合水凝胶体系不仅可以响应葡萄糖的浓度水平变化实时调节控制胰岛素的释放，而且具有较好的生物相容性，是一种具有一定应用前景的胰岛素类大分子药物的递送系统．
Abstract_English:The development of glucose-sensitive hydrogels for the delivery of insulin has important significance for the treatment of diabetes. However，insulin has unique physicochemical properties and administration requirements，so a single-polymer-hydrogel delivery system with highly efficient massive load capacity，and accurate long-acting controlled release is difficult to achieve. Based on glucose-sensitive phenyboronic acid(PBA)，we prepared PBA-surface-modified poly(lactic-co-glycolic acid)porous microspheres(PBA-PLGA SM)and then mixed them with polyvinyl alcohol(PVA)solution to develop a novel glucose-sensitive porous-microsphere/PVA(PBA-PLGA SM/PVA) hybrid hydrogel. This PBA-PLGA SM/PVA hydrogel combines the advantages of polymeric hydrogels of target location and stimuli-response function with the efficient drug-loading properties of porous microspheres. More importantly，the main functions of hydrogels for insulin delivery，including efficient loading，controlled release，and stimuli response，were creatively designated to different units of this new drug delivery system to facilitate the respective functions of the porous microspheres，glucose-sensitive PBA polymers，and polymeric hydrogels. We then studied the prepared PBA-PLGA SM/PVA hydrogel with respect to its properties，glucose sensitivity，and release characteristics as well as its in vitro degradation and cytotoxicity. The research results show that in response to the glucose concentration levels，the composite hydrogel system not only adjusts and controls the release of insulin in real time，but also has good biocompatibility. This novel glucose-sensitive hybrid hydrogel represents a promising implantable platform for diabetes therapy. The research results presented here will facilitate the development of similar drug delivery systems for other peptide and protein drugs.
Keyword_Chinese:硼酯键；复合凝胶；葡萄糖敏感性；胰岛素释放；糖尿病
Keywords_English:boronate bonds；hybrid hydrogel；glucose sensitivity；insulin delivery；diabetes

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