Validation of a Pharmacokinetic Model of Colon-specific Drug Delivery and the Therapeutic Effects of Chitosan Capsules Containing 5-Aminosalicylic Acid on 2,4,6-Trinitrobenzenesulphonic Acid-induced Colitis in Rats

Abstract

A pharmacokinetic model of colon-specific drug delivery developed in a previous study has been validated by use of 5-aminosalicylic acid (5-ASA) as a model anti-inflammatory drug.The simulation curves obtained from the pharmacokinetic model were in good agreement with experimental data obtained after oral administration of 5-ASA-containing chitosan capsules. The concentrations of 5-ASA in the large intestinal mucosa after drug administration were higher than after administration of the drug in carmellose suspension. We then attempted colon-specific delivery of an anti-ulcerative colitis drug, in chitosan capsules, to accelerate healing of 2,4,6-trinitrobenzenesulphonic acid sodium salt (TNBS)-induced colitis in rats. To confirm this therapeutic model, salazosulphapyridine (SASP), a commercially available 5-ASA prodrug, was used as positive control. Colonic injury and inflammation were assessed by measuring myeloperoxidase activity and visual assessment (damage score), respectively. Because SASP is effective against TNBS-induced colitis in rats, use of the SASP-sensitive TNBS-induced colitis model validated the therapeutic effects of 5-ASA-containing chitosan capsules, which were signiicantly better than those of a suspension of the drug in carmellose.These findings suggest that our pharmacokinetic model of colon-specific drug delivery can accurately evaluate this colon-specific delivery system and that 5-ASA-containing chitosan capsules are more effective than other 5-ASA formulations for treatment of TNBS-induced colitis in rats.