庚酰化乙二醇壳聚糖温敏性水凝胶的制备及其药物缓释  

Preparation of heptanoylated glycol chitosan thermo-sensitive hydrogel for sustained drug release

作　　者：韩晓杰 李征征 HAN Xiaojie;LIZhengzheng(School of Chemical Engineering and Materials,Tianjin University of Science and Technology,Tianjin 300457,China;Yishui County No.4 Middle School,Linyi 276405,China;State Key Laboratory of Molecular Engineering of Polymers,Fudan University,Shanghai 200433,China)

机构地区：[1]天津科技大学化工与材料学院,天津300457 [2]沂水县第四中学,临沂276405 [3]复旦大学聚合物分子工程国家重点实验室,上海200433

出　　处：《复合材料学报》2024年第5期2674-2682,共9页Acta Materiae Compositae Sinica

基　　金：2018年度天津市教委科研计划项目(2018KJ110);2021年天津市研究生科研创新项目(2021YJSS048)。

摘　　要：为了制备一种物理交联的温敏性水凝胶,本文选择水溶性乙二醇壳聚糖(GC)作为基体,通过庚酸酐与GC分子链上的氨基进行酰化反应实现改性,合成了具有不同庚酰度(DS)的庚酰化乙二醇壳聚糖(HAGC)。庚酸酐与GC分子链上氨基的进料摩尔比在0.2~0.25之间,DS介于26.4%~31.5%。通过在GC骨架上引入疏水性庚酰基团,提高GC在有机溶剂中的溶解度和体外生物降解性,而且还引入了温敏性溶胶-凝胶转变性质。HAGC通过分子间相互作用(氢键和亲疏水相互作用)发生物理交联,响应环境温度变化而发生溶胶-凝胶相变,通过改变HAGC的DS和溶液浓度,可有效调节HAGC水凝胶的溶胶-凝胶转变温度处于25~37℃之间。HAGC水凝胶具有三维多孔结构,随着DS增加,HAGC水凝胶的交联密度增大、溶胀比降低、药物释放速率减慢。HAGC水凝胶对吉西他滨具有缓释作用,药物释放时间可达5天,药物释放率达到70%~91%。HAGC水凝胶以其优良的温敏性能,在药物注射载体领域具有重要的应用价值。In order to prepare a physically cross-linked thermo-sensitive hydrogel,in this paper,water-soluble glycol chitosan(GC)was selected as the matrix,the heptanoylated glycol chitosan(HAGC)with different degrees of heptanoylation(Ds)were synthesized by acylation modification through amide coupling reaction between heptanoic anhydride and amino groups on the molecular chain of GC.The results show that the feed molar ratio of heptanoic anhydride to the amino group on GC is between 0.2 and 0.25,and DS is modulated from 26.4%to 31.5%.By the introduction of hydrophobic acetyl groups on the backbone of GC,it was not only found that such derivatiza-tion would improve the solubility in organic solvents and in vitro biodegradability of GC,but also import new at-tractive properties such as thermo-sensitive sol-gel transition properties.HAGC was physically cross-linked through intermolecular interactions,including hydrogen bonding and hydrophilic and hydrophobic interactions.Thus,HAGC could undergo sol-gel phase transition in response to ambient temperature changes.By changing the DS and solution concentration of HAGC,the sol-gel transition temperature of HAGC hydrogel was effectively adjusted between room temperature and human body temperature(25-37'C).The HAGC hydrogel had the threedimensional porous structure.As the DS increase,the crosslink density of the HAGC hydrogel increased,the swelling ratio decreased,and the drug release rate slowed down.The HAGC hydrogel had a slow-release effect on the drug gemcitabine,and the drug release time could reach 5 days,and the drug release rate was up to 70%-91%.Therefore,HAGC hydrogel has important application value in biomedical fields such as drug injection and sustained-release carrier due to its excellent thermo-sensitive properties.

关 键 词：乙二醇壳聚糖 庚酰化 温敏性水凝胶 溶胶-凝胶转变 药物缓释 

分 类 号：O63[理学—高分子化学] TB332[理学—化学]