Enzymatically degradable and pH-sensitive hydrogels for colon-targeted oral drug delivery. I. Synthesis and characterization

Cylindrical hydrogels, composed of starch and poly(acrylic acid), were synthesized, and their swelling behavior was studied as a function of the pH of the medium. The gels underwent a sharp transition from Fickian swelling behavior (swelling exponent n = 0.30) to non-Fickian swelling behavior (n = 0.96) as the pH of the swelling medium changed from 2.0 to 7.4. The hydrogels also underwent partial enzymatic degradation in an amylase-containing medium of pH 7.4 at 37degreesC. The effects of the enzyme concentration in the swelling media, the amount of starch present in the gel, the initial water content, the degree of crosslinking, and the diameter of cylindrical hydrogels on the degradation behavior were studied. The degradation of the gels followed Michaelis-Menten kinetics, and the value of the Menten constant was 41.62 X 10(-2). The gels exhibited minimum swelling in an acidic pH medium through the formation of a complex hydrogen-bonded structure and underwent enzymatic degradation in a medium of pH 7.4 (i.e., simulating intestinal fluid) along with chain-relaxation-controlled swelling. Therefore, the gels have potential for colon-targeted drug delivery. (C) 2004 Wiley Periodicals, Inc.