title: Bioadhesive pellets increase local 5-aminosalicylic acid concentration in experimental colitis.
abstract: Topical delivery of 5-aminosalicylic acid (5-ASA) to the colonic mucosa is important in order to achieve effective drug concentration in the site of inflammation and to minimize its systemic availability. 5-ASA loaded pellets were prepared by an extrusion/spheronization method. Mucoadhesive biopolymer chitosan was incorporated into the pellets, and drug delivery to the colon was controlled by the pH-sensitive polymer Eudragit® FS. Dissolution profiles of coated pellets revealed no drug release at pH 1.2 within 2h and release as intended in the simulated distal ileum and colon. In vivo, chitosan-core drug loaded pellets (AMCh) showed 2.5-fold higher drug metabolite concentration than after chitosan free pellets (AM) administration in the inflamed colonic tissue. Additionally, AMCh demonstrated decreased in AUC in colitis group (1507 ± 400 ng h/ml) compared with AM (1907 ± 122 ng h/ml). In terms of therapeutic efficiency, administration of pellets markedly decreased the colon/body weight ratio (colitis: 0.0355 ± 0.0028; AM 0.0092 ± 0.0033; AMCh 0.0086 ± 0.0022) and myeloperoxidase activity (colitis: 3212 ± 294 U/g tissue; AM 796 ± 211 U/g; AMCh 552 ± 319 U/g). Bioadhesive chitosan pellets showed additional beneficial properties for colonic 5-ASA delivery in the treatment of inflammatory bowel disease by increasing the drug concentration locally.
authors.affiliation: Department of Pharmaceutics, University of Veterinary and Pharmaceutical Sciences, Brno, Czech Republic.
authors.forename: Tereza
authors.initials: T
authors.lastname: Bautzová
authors.forename: Miloslava
authors.initials: M
authors.lastname: Rabišková
authors.forename: Arnaud
authors.initials: A
authors.lastname: Béduneau
authors.forename: Yann
authors.initials: Y
authors.lastname: Pellequer
authors.forename: Alf
authors.initials: A
authors.lastname: Lamprecht
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000737:chemistry; D001704:Biopolymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism*; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D004343:Drug Implants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
chemical_list: D000893:Anti-Inflammatory Agents; D001704:Biopolymers; D004343:Drug Implants; D019804:Mesalamine; D048271:Chitosan; D009195:Peroxidase