Preparation Of Carboxymethyl Chitosan Grafted Polyacrylic Acid PH-Sensitive Hydrogel

Smart hydrogel is a kind of crosslinked copolymers, which can response to the external stimulus, such as: pH, temperature, light, and electric field, et al. pH-sensitive hydrogel can swell or shrink with the changing of environmental pH, which can intelligently deliver model drugs to target sites. In this study, a novel pH-sensitive hydrogel(CMC-g-PAA) was fabricated via a thermal initiated radical polymerization with acrylic acid(AA) and carboxymethyl chitosan(CMC) as monomers. In the fabrication, the monomer ratios, dosage of crosslinking agents, amount of initiators, reaction temperature, and reaction time were studied, and the optimal preparation technology of CMC-g-PAA hydrogel was determined. The structure of CMC-g-PAA copolymers was characterized with a STS-135 Fourier transform infrared spectroscopy(FTIR). The inner structure of the CMC-g-PAA hydrogel was observed with a S-4800-I scanning electronic microscope(SEM). Results showed that the CMC-g-PAA copolymer was successfully synthesized, and the CMC-g-PAA hydrogel had a network structure. Bovine serum albumin(BSA), as a model drug, was encapsulated in the CMC-g-PAA hydrogel. The release behavior of BSA from BSA-loaded CMC-g-PAA hydrogel was performed. Studied showed that such medicated hydrogel had an excellent pH responsibility, because less than 20 % of BSA was released into phosphate buffer solution(pH 1.2), but over 90 % of BSA was diffused into PBS(pH 7.4). Meanwhile, insulin(INS) was also employed as another model drug, and encapsulated into the CMC-g-PAA hydrogel. The INS-loaded CMC-g-PAA hydrogel showed the similar release profile with that of BSA-loaded CMC-g-PAA hydrogel. The in vivo hyperglycemic effect of oral INS-loaded CMC-g-PAA hydrogel was studied with male Wistar rates as glycosuric animal models. Studies found that INS-CMC-g-PAA hydrogel could targeted release INS in intestinal tracts, which protected INS from destroying by pepsin, and maintained its bioactivity. The adsorbed INS via intestinal mucosa exhibited an excellent hyperglycemic effect. Therefore, the CMC-g-PAA hydrogel has a good application as the carrier of protein drugs.