title: Chitosan capsules for colon-specific drug delivery: enhanced localization of 5-aminosalicylic acid in the large intestine accelerates healing of TNBS-induced colitis in rats.
abstract: The objective of this study was to achieve the colon-specific delivery of an anti-ulcerative colitis drug using chitosan capsules and to accelerate healing of 2,4,6-trinitrobenzene sulfonic acid sodium salt (TNBS)-induced colitis in rats. 5-Aminosalicylic acid (5-ASA) was used as a model of an anti-inflammatory drug. The gastrointestinal transit of chitosan capsules was determined by counting the number of capsules in the gastrointestinal lumen by celiotomy at certain times after their oral administration to rats. The chitosan capsules reached the large intestine 3.5 h after oral administration in rats. We studied the release of 5-ASA from chitosan capsule by the Japan Pharmacopoeia (JP) rotating basket method. The release of 5-ASA from the chitosan capsule markedly increased in the presence of rat cecal contents. After oral administration of chitosan capsules containing 5-ASA, the concentrations of 5-ASA in the large intestinal mucosa were higher than those in the CMC suspension. For the treatment of colitis in rats, 5-ASA was orally administered using chitosan capsules or a carboxy methyl cellulose (CMC) suspension to TNBS-induced rats. The colonic injury and inflammation were assessed by measuring the myeloperoxidase (MPO) activities, colon wet weight/body weight (C/B) ratio and the damage score, respectively. When 5-ASA was orally administered using chitosan capsules in TNBS-induced colitis rats, we found better therapeutic effects with 5-ASA than with a 5-ASA CMC suspension, as evaluated by the MPO activities, C/B ratio and the damage score. In conclusion, chitosan capsules may be useful carriers for the colon-specific delivery of anti-inflammatory drugs including 5-ASA and the healing of TNBS-induced colitis in rats.
authors.affiliation: Department of Biopharmaceutics, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Tozaki
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Odoriba
authors.forename: Naoki
authors.initials: N
authors.lastname: Okada
authors.forename: Takuya
authors.initials: T
authors.lastname: Fujita
authors.forename: Akira
authors.initials: A
authors.lastname: Terabe
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Suzuki
authors.forename: Susumu
authors.initials: S
authors.lastname: Okabe
authors.forename: Shozo
authors.initials: S
authors.lastname: Muranishi
authors.forename: Akira
authors.initials: A
authors.lastname: Yamamoto
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002214:Capsules; D002266:Carboxymethylcellulose Sodium / Q000493:pharmacokinetics; D002686:Chitin / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D048271:Chitosan; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D004337:Drug Carriers / Q000493:pharmacokinetics; D007408:Intestinal Absorption; D008297:Male; D019804:Mesalamine / Q000493:pharmacokinetics* / Q000627:therapeutic use; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution; D014302:Trinitrobenzenesulfonic Acid / Q000633:toxicity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D004337:Drug Carriers; D002686:Chitin; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid; D048271:Chitosan; D009195:Peroxidase; D002266:Carboxymethylcellulose Sodium