title: 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 significantly 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.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tozaki
authors.forename: T
authors.initials: T
authors.lastname: Fujita
authors.forename: T
authors.initials: T
authors.lastname: Odoriba
authors.forename: A
authors.initials: A
authors.lastname: Terabe
authors.forename: S
authors.initials: S
authors.lastname: Okabe
authors.forename: S
authors.initials: S
authors.lastname: Muranishi
authors.forename: A
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002214:Capsules; D002686:Chitin / Q000031:analogs & derivatives* / Q000737:chemistry; D048271:Chitosan; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004337:Drug Carriers; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008954:Models, Biological; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012460:Sulfasalazine / Q000493:pharmacokinetics / Q000627:therapeutic use; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D004337:Drug Carriers; D002686:Chitin; D012460:Sulfasalazine; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid; D048271:Chitosan