Key Laboratory of Functional Polymer Materials, Institute of Polymer Chemistry, Nankai University , Tianjin 300071, China.
ACS Appl Mater Interfaces. 2014 Mar 12;6(5):3640-7. doi: 10.1021/am405927f. Epub 2014 Feb 3.
The synthesis and characterization of multi-sensitive polymers for use as injectable hydrogels for controlled protein/drug delivery is reported. A series of biodegradable multi-sensitive poly(ether-urethane)s were prepared through a simple one-pot condensation of poly(ethylene glycol), 2,2'-dithiodiethanol, N-methyldiethanolamine, and hexamethylene diisocyanate. The sol-gel phase transition behaviors of the obtained copolymers were investigated. Experimental results showed that the aqueous medium comprising the multi-segment copolymers underwent a sol-to-gel phase transition with increasing temperature and pH. At a certain concentration, the copolymer solution could immediately change to a gel under physiological conditions (37 °C and pH 7.4), indicating their suitability as in situ injectable hydrogels in vivo. Insulin was used as a model protein drug for evaluation of the injectable hydrogels as a site-specific drug delivery system. The controlled release of insulin from the hydrogel devices was demonstrated by degradation of the copolymer, which is modulated via the 2,2'-dithiodiethanol content in the poly(ether-urethane)s. These hydrogels having multi-responsive properties may prove to be promising candidates for injectable and controllable protein drug delivery devices.
本文报道了一种可用于控制蛋白质/药物递释的可注射水凝胶的多响应性聚合物的合成与表征。通过聚乙二醇、2,2'-二硫二乙醇、N-甲基二乙醇胺和六亚甲基二异氰酸酯的简单一锅缩合反应，制备了一系列可生物降解的多响应性聚（醚-氨酯）。研究了所得共聚物的溶胶-凝胶相转变行为。实验结果表明，包含多段共聚物的水介质在升高温度和 pH 值时经历溶胶-凝胶相转变。在一定浓度下，共聚物溶液在生理条件（37°C 和 pH 值 7.4）下可立即转变为凝胶，表明其适合作为体内原位可注射水凝胶。胰岛素被用作模型蛋白质药物，以评估作为局部药物递送系统的可注射水凝胶。通过共聚物的降解来证明胰岛素的控制释放，这是通过聚（醚-氨酯）中的 2,2'-二硫二乙醇含量来调节的。这些具有多响应性的水凝胶可能是可注射和可控蛋白质药物递送装置的有前途的候选物。
