化学交联葡萄糖基取代聚膦腈水凝胶制备和胰岛素释放研究  

PREPARATION OF A GLUCOSE-SENSITIVE POLYPHOSPHAZENE HYDROGEL AND ITS INSULIN RELEASE BEHAVIOR

作　　者：刘志玲[1] 张力[1] 洪挺[1] 蔡晴[1] 金日光[1] 

机构地区：[1]北京市新型高分子材料制备与加工重点实验室北京化工大学,北京100029

出　　处：《高分子学报》2010年第3期340-346,共7页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号50873012)资助项目

摘　　要：在合成了葡萄糖基和甲氧乙氧基共取代聚膦腈的基础上,进一步通过向聚膦腈主链引入一定量带自由氨基的取代基,与戊二醛反应交联后,获得了具有化学交联点的聚膦腈水凝胶.该水凝胶与伴刀豆球蛋白(Con A)结合后,水凝胶的溶涨平衡性能表现出对葡萄糖浓度的依赖性.将负载有胰岛素的聚膦腈水凝胶交替置于含不同葡萄糖浓度(4 mg/mL和1 mg/mL)的介质中,可检测到在高浓度葡萄糖环境下,胰岛素的释放明显加快,而当葡萄糖的浓度降低后,在一段时间内几乎检测不到胰岛素的释放,但随着浸泡时间的延长,仍会逐渐出现胰岛素从凝胶缓慢扩散释放的现象.以上研究表明,化学交联的葡萄糖基取代聚膦腈水凝胶可用于对胰岛素的葡萄糖响应释放.A novel kind of biodegradable glucose-sensitive polyphosphazene hydrogel has been prepared basing on both the chemical crosslinking and the specific interaction between polymerbound glucose and concanavalin A （Con A）.Glucosyl-co-methoxyethoxyl-co-2-（2-aminoethoxy）ethoxyl substituted polyorgano-phosphazene was synthesized by subsequently nucleophilic substitution of polydichlorophosphazene with 2-[2-（（tert-butoxycarbony1）amino）ethoxy]ethanol,diisopropylidene D-glucose and methoxyethanol,which was followed by deprotection treatment with trifluoroacetic acid to restore glycosyl and free amino groups.A chemical crosslinked hydrogel was obtained by reacting the above polymer with glutaraldehyde.The polyphazene hydrogel showed good swelling behavior in phosphate buffer solutions,and exhibited glucose-sensitive water absorption after Con A being loaded.No macroscopic deformation could be observed by immersing the Con A-loaded polyphoaphzene hydrogel into aqueous solution with high content of glucose for the presence of chemical crosslinking.The release rate of insulin from this polyphosphazene hydrogel depended on the concentration of free glucose in medium obviously.As the glucose concentration was increased from 1 mg/mL to 4 mg/mL,the release rate of insulin from the hydrogel increased,whereas,the release rate decreased when the glucose concentration was reduced to 1 mg/mL.The results demonstrated the possibility of using chemical crosslinked glucose-bearing polyphosphazene to prepare glucose-sensitive hydrogels in combination with Con A and to regulate the insulin release as a function of the free glucose concentration in the environment.

关 键 词：葡萄糖响应性 聚膦腈 水凝胶 

分 类 号：R943[医药卫生—药剂学]