- Chondroitin sulfate, a soluble mucopolysaccharide utilized as a substrate by the bacteroid inhabitants of the colon, was cross-linked and formulated in a matrix form with indomethacin as a drug marker. Three levels of cross-linkage were used. Cross-linkage was characterized qualitatively by IR spectral analysis and by UV absorbance shifts in hydroalcoholic solutions; it was also characterized quantitatively by comparing the amount of methylene blue remaining after adsorption (at equilibrium) onto the cross-linked product vs that remaining after adsorption onto untreated Chondroitin. The indomethacin release kinetics from the various formulations was analyzed in phosphate-buffered saline (PBS) with and without rat caecal content at 37°C under a CO 2 atmosphere. In separate experiments the caecal content was sonicated to cause lysis of the bacterial cell membranes. The drug release profiles indicated a constant rate of biodegradation in the presence of rat caecal content, and diffusion-driven release from the matrix's surface area in PBS control. Prolonged incubation in PBS with rat caecal content increased drug release, and by 28 h the released indomethacin levels were significantly higher than those in the PBS controls. The maximal cumulative percent release values for the PBS controls were: 30.1 ± 10.0, 19.7 ± 15.0, 9.0 ± 4.1 for the three levels of cross-linkage of the Chondroitin sulfate carriers, respectively, while those for the caecal content media were 71.0 ± 19.0, 48.7 ± 35.0, and 22.5 ± 7.9, respectively. It was concluded that the indomethacin release from these systems was dependent upon the biodegradation action of the caecal content. The linear correlation between the degree of cross-linkage and the amount of drug released in the presence of caecal content suggests that drug release in the colon can be controlled by adjusting the relative amounts of the variously cross-linked Chondroitin sulfate formulations in the matrices.