pH/盐双敏感型聚离子液体凝胶的制备及对环丙沙星的控制释放

Preparation of pH/salt dual-sensitive polyionic liquid gels andcontrolled release of ciprofloxacin

以不同烷基侧链的N-乙烯基咪唑类离子液体为单体,设计合成了3种具有pH/盐双敏感性的交联网状孔洞结构的聚咪唑类离子液体凝胶(PC_(n)vimBr,n=2,4,6)。在微观结构、溶胀特性和刺激响应行为研究基础上,探讨了侧链微增长对聚离子液体凝胶结构与性能的调节控制,并根据凝胶的构效关系情况进行相应药物的体外控制释放研究,研究表明,PC_(n)vimBr凝胶具有良好的pH/盐刺激双响应性以及溶胀可逆性。在pH=7.4的弱碱性环境下,三种聚离子液体凝胶均具有较强的敏感性及溶胀可逆性,其中PC_(2)vimBr凝胶的pH响应性最为敏感,其平衡溶胀率高达1422.3%。同时,以NaCl盐溶液为模拟模型,相对而言,PC_(2)vimBr凝胶在弱碱性条件下具有良好的盐敏感性。此外,结合人体肠道呈弱碱性特点,以肠道杀菌药物环丙沙星(CIP)为载药模型,在pH=7.4时药物控制释放的体外模拟实验研究发现,PC_(2)vimBr凝胶10 h内的累积释放率为67.78%,是PC_(4)vimBr、PC_(6)vimBr凝胶的1.42和3.38倍,这与pH/盐刺激双响应性的研究结果一致。因此,烷基侧链微增长对凝胶结构具有较强的调控作用,pH/盐双敏感性的PC_(2)vimBr凝胶在肠道杀菌药物的控制释放具有潜在的应用价值。

Using N-vinylimidazole ionic liquids with different alkyl side chains as monomers,three types of polyimidazole ionic liquid gels(PC_(n)vimBr,n=2,4,6)with cross linked mesh pore structure are designed.Based on the study of microstructure,swelling characteristics and stimulus response behavior,the adjustment and control of the micro-growth of side chains on the structure and performance of polyionic liquid gels are discussed.According to the structure-activity relationship of gels,controlled release of corresponding drugs is studied in vitro.Studies have shown that PCnvimBr gels have good pH/salt stimulus responsiveness and swelling reversibility.In a weakly alkaline environment of pH=7.4,the three polyionic liquid gels all have strong stimulus responsiveness and swelling reversibility.Among them,the pH responsiveness of PC_(2)vimBr gel is the most sensitive,and its equilibrium swelling rate is as high as 1422.3%.At the same time,using NaCl salt solution as a simulation model,relatively speaking,PC_(2)vimBr gel has good salt stimulation response under weakly alkaline conditions.In addition,combining with the weakly alkaline characteristics of the human intestine,the intestinal bactericidal drug ciprofloxacin(CIP)is used as the drug-loading model.The in vitro simulation experiment of drug controlled release at pH=7.4 finds that within 10 h,the cumulative release rate of the PC_(2)vimBr gel is up to 67.78%,which is 1.42 and 3.38 times higher than that of PC4vimBr and PC6vimBr gels.The above consequence is consistent with the results of the pH/salt stimulation responsiveness study.Therefore,the micro-growth of alkyl side chains has a strong regulatory effect on the gel structure,and the pH/salt dual stimulus responsive PC_(2)vimBr gel has potential application value in the controlled release of intestinal bactericidal drugs.