Fabrication and evaluation of a novel polymeric hydrogel of carboxymethyl chitosan-g-polyacrylic acid (CMC-g-PAA) for oral insulin delivery

Abstract

A novel pH-sensitive hydrogel consisting of carboxymethyl chitosan (CMC) and acrylic acid (AA) was fabricated via free radical grafting polymerization. The effective factors on the swelling ratio of the hydrogel were studied. The successful fabrication of the CMC-g-PAA hydrogel was confirmed by Fourier transform infrared spectroscopy (FTIR). The inner morphology of the final hydrogel was observed with scanning electron microscopy (SEM). Insulin (INS) was used as a model drug and encapsulated into the CMC-g-PAA hydrogel. The release profile of the INS loaded-CMC-g-PAA (INS-CMC-g-PAA) hydrogel was obtained in phosphate buffer solution (PBS) at pH 1.2 and 7.4. The hypoglycemic effect of orally administered INS-CMC-g-PAA hydrogel was also studied. SEM photographs showed that the CMC-g-PAA hydrogel had a 3D network structure. In vitro release tests showed that only 16.3 ± 2.6% of INS was released at pH 1.2, while over 93.2 ± 3.8% of INS was diffused into PBS (pH 7.4). This phenomenon illustrated that the INS-CMC-g-PAA hydrogel had a good pH response, and could direct INS to release in basic environments. The animal experiments demonstrated that the oral INS-CMC-g-PAA hydrogel had a persistent and effective hypoglycemic effect. Therefore, the CMC-g-PAA hydrogel has a potential application for the oral delivery of protein drugs.