羧甲基壳聚糖接枝聚丙烯酸水凝胶的制备及体内外评价

Preparation of carboxymethyl chitosan grafted polyacrylic acid hydrogel and its evaluation in vitro and in vivo

以丙烯酸(AA)和羧甲基壳聚糖(CMC)为单体,通过热引发自由基接枝共聚反应,制备了一种新型pH敏感的羧甲基壳聚糖接枝聚丙烯酸(CMC-g-PAA)水凝胶。FT-IR结果表明成功实现了聚合反应,溶胀性实验表明CMC-g-PAA水凝胶具有明显的pH敏感性。以胰岛素(INS)为模型药物,将其负载到CMC-g-PAA水凝胶中,得到了载药量为216.5mg/g的载药凝胶。体外释放曲线表明:在pH值为1.2的条件下,2h后INS的累计释放量为(16.3±2.6)%;在pH值为7.4的环境中,2h后INS的累计释放量达到(57.2±3.5)%。说明载药凝胶可以在肠道环境中靶向释放INS,避免INS被胃酸和胃蛋白酶破坏。动物实验结果表明,负载INS水凝胶具有良好的降血糖效果。CMC-g-PAA水凝胶与Caco-2细胞共同培养,细胞存活率接近100%,表明水凝胶对Caco-2细胞没有细胞毒性。CMC-g-PAA水凝胶在蛋白或多肽类药物定位递送方面具有优良的应用前景。

A novel pH-sensitive carboxymethyl chitosan graft polyacrylic acid（CMC-g-PAA）hydrogel is fabricated via a free radical heat-initiated graft copolymerization reaction with acrylic acid（AA）and carboxymethyl chitosan（CMC）as monomers.The polymerization is successful,which is confirmed via fourier transform infrared spectroscopy（FT-IR）.The result of swelling experiment indicates that the final CMC-g-PAA hydrogel has significant pH-sensitivity.Insulin（INS）,as a model drug,is loaded into the hydrogel and 216.5mg/g incorporation of INS is obtained.In vitro release profiles suggest that INS release is（16.3±2.6）% when pH is 1.2after 2h.INS release is（57.2±3.5）%in PBS with pH of 7.4after the next 2h.The study indicates that the CMC-g-PAA hydrogel loaded with INS could targeted deliver INS in intestinal,and avoid that INS isdestroyed by gastric acid and pepsin.The experiment result on animals indicates that the CMC-g-PAA hydrogel loaded with INS has hypoglycemic effects.With different concentrations of CMC-g-PAA hydrogel co-cultured with Caco-2cells,the cell survival rates are close to 100%,which indicates that the hydrogel has no cytotoxicity.In sum,the novel CMC-g-PAA hydrogel has a prospective application in the specific-site delivery of proteins and peptides.