Bioadhesive pellets increase local 5-aminosalicylic acid concentration in experimental colitis

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 (R) FS. Dissolution profiles of coated pellets revealed no drug release at pH 1.2 within 2 h 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. (C) 2012 Elsevier B.V. All rights reserved.