Mucoadhesive and pH-responsive behavior of gelatin containing hydrogels for protein drug delivery applications

Abstract

Novel gelatin-containing polymer hydrogels that can be used as mucoadhesive delivery systems were developed. Poly(acrylic acid) hydrogels were modified by copolymerizing gelatin as adhesion promoter, to improve the adhesion to the mucus layer and the synthesized copolymer of acrylic acid (AA) and methacrylated gelatin (GelMA) were designated as P(AA-co-GelMA). The pH-sensitivity and the mucoadhesive property of the P(AA-co-GelMA) hydrogel were investigated as carries of an oral protein delivery system activated by pH changes of the human GI tract. There was a drastic change in the weight swelling ratio of P(AA-co-GelMA) hydrogels at a pH of around 5, that is, low swelling ratios at a pH below 5, while high swelling ratios at a pH greater than 5. In addition, the swelling ratio increased at a pH above 5, when the AA content in the hydrogel increased. In mucoadhesive experiments using the rheometer, when the GelMA concentration in the P(AA-co-GelMA) hydrogel increased, the maximum force of detachment increased, indicating that the mucoadhesion of the hydrogel was improved. The P(AA-co-GelMA) hydrogels also showed a pH-responsive release behavior. The ratio of the cumulative amounts of Rh-B released from P(AA-co-GelMA) hydrogels at pH 2.6 to pH 7.0 increased, when the AA content in the hydrogel decreased.