Gastrointestinal distribution and absorption behavior of Eudragit-coated chitosan-prednisolone conjugate microspheres in rats with TNBS-induced colitis.

Conjugate of chitosan and succinyl-prednisolone, termed Ch-SP, was synthesized, and Ch-SP microspheres (Ch-SP-MS) and Eudragit L100-coated Ch-SP-MS (Ch-SP-MS/EuL) were prepared using Ch-SP. Ch-SP-MS and Ch-SP-MS/EuL had a mean size of 1.5 and 26.6microm, respectively, and a drug content of 4.6 and 3% (w/w), respectively. Prednisolone (PD) was released very slow in JP 14 first fluid (pH 1.2), and gradually in JP 14 second fluid (pH 6.8). The addition of cecal or colonic content did not accelerate the release. Rats with 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced colitis were used in animal studies. Gastrointestinal distribution and plasma concentration were investigated by oral administration of PD alone and Ch-SP-MS/EuL. For PD alone, PD was distributed at the stomach and small intestine, and disappeared from the gastrointestinal tracts within 8h. When administering Ch-SP-MS/EuL, the drug was distributed mainly in the lower intestine between 3 and 24h. Plasma concentration was much lower in Ch-SP-MS/EuL than in PD alone, suggesting lower toxic side effects of Ch-SP-MS/EuL. Thus, Ch-SP-MS/EuL delivered PD specifically near the diseased site and PD was released gradually, with much less plasma concentration of PD. Ch-SP-MS/EuL are suggested as a useful delivery system to the site of inflammatory bowel disease.