生理pH下可控释放胰岛素的温度/葡萄糖双响应可注射复合水凝胶

Injectable Temperature-and Glucose-responsive Composite Hydrogels forControlled Release of Insulin at Physiological pH

成功制备了能够在生理pH下快速响应葡萄糖的Alg-g-PNA/Alg-g-PNIPAM可注射复合水凝胶体系。研究了复合体系的温度和葡萄糖响应特性,结果表明,该体系在10℃时为溶胶态,37℃下转变为凝胶态;在pH=7.4条件下,随葡萄糖浓度增加,复合体系的低临界溶解温度(LCST)逐渐升高,葡萄糖响应性良好。考察了复合体系的流体力学特性,结果表明,复合水凝胶体系具有良好的热响应可逆性与自修复性。最后,探究了复合体系的体外药物释放行为,结果表明,48 h内,复合水凝胶在高血糖浓度下胰岛素的累积释放远高于低血糖浓度下胰岛素的累积释放,且能够较好地响应高血糖与正常血糖间的循环交替变化。该复合体系通过简单的环境温度刺激或者葡萄糖浓度刺激即可实现溶胶-凝胶转变,且能够在生理温度和生理pH下及时响应血糖浓度变化,为基于血糖响应的胰岛素体内自调节给药系统的开发提供了一种新策略。

The Alg-g-PNA/Alg-g-PNIPAM injectable composite hydrogel system,which can respond to glucose at physiological pH,is successfully prepared in this work.The temperature-and glucose-responsive properties of the composite system are studied.The results show that the composite system is in the sol state at 10℃,and turns into the gel state at 37℃.The low critical solution temperature(LCST)of the composite system increases gradually with the increase of glucose concentration at pH=7.4,and the glucose response is good.The hydrodynamic properties of the composite system are investigated.The results show that the composite system has good thermal reversibility and self-healing property.Finally,the in vitro drug release performance of the composite system is investigated.The results show that the cumulative insulin release percentages from the composite system at high glucose concentrations are much higher than that at low glucose concentrations within 48 h.And the composite gel can also adapt to the circulation between high blood sugar and normal blood sugar.The composite system can realize the sol-gel phase transition only through simple ambient temperature or glucose concentration stimulation and can respond to blood glucose timely at physiological temperature and pH,which provides a new strategy for the development of self-regulating insulin delivery system based on blood glucose response.