Using pH-sensitive hydrogels containing cubane as a crosslinking agent for oral delivery of insulin

The goal of oral insulin delivery devices is to protect the sensitive drug from proteolytic degradation in the stomach and upper portion of the small intestine. Copolymers of 2-hydroxyethyl methacrylate (HEMA) and methacrylic acid (MAA) based hydrogels containing 2, 4, and 6% of a crosslinking agent (CA) were studied as drug delivery systems. Cubane-1, 4-dicarboxylic acid (CDA) was linked to two HEMA groups as CA. Radical copolymerizations of HEMA and MAA with the various ratios of CA were performed at 70 degrees C. The compositions of the crosslinked three-dimensional polymers were determined using Fourier transform infrared spectroscopy. Glass-transition temperature of the network polymers was determined calorimetrically. The effect of copolymer composition on the swelling behavior and hydrolytic degradation was studied in simulated gastric fluid (pH 1) and simulated intestinal fluid (pH 7.4). The swelling and hydrolytic behavior of the copolymers was dependent on the content of MAA groups and caused a decrease in gel swelling in simulated gastric fluid or an increase in gel swelling in simulated intestinal fluid. The drug-release profiles indicate that the amount of drug release depends on their degree of swelling and crosslinking. (c) 2005 Wiley Periodicals, Inc.