羧甲基壳聚糖接枝聚丙烯酸水凝胶的制备及体内外评价

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。

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

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 216.5 mg/g incorporation of INS is obtained. In vitro release profiles suggest that INS release is (16.3±2.6)% when pH is 1.2 after 2 h. INS release is (57.2±3.5)% in PBS with pH of 7.4 after the next 2 h. The study indicates that the CMC-g-PAA hydrogel loaded with INS could targeted deliver INS in intestinal, and avoid that INS is destroyed 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-2 cells, 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.