Colonic delivery of carboxyfluorescein by pH-sensitive microspheres in experimental colitis

The colonic drug delivery in inflammatory bowel disease (IBD) by microcarriers has been suggested over the past decade; however, pharmacokinetic and biopharmaceutical details are hardly known. A model colitis was induced to male Wistar rats by trinitrobenzenesulfonic acid. Carboxyfluorescein (CF) was entrapped into microspheres (MS) prepared with the pH-sensitive polymer Eudragit (R) S100, in order to simulate drug delivery to the colon. Pharmacokinetic behaviour of CF-MS was compared to oral or rectal administration of CF as solution in healthy or colitis group. Colitis lowered the oral bioavailability of CF solution, compared to healthy controls (healthy: 8.4 +/- 1.5; colitis: 3.0 +/- 0.9; all mu g/ml h), and similar results were obtained after rectal administration of CF solution (healthy: 5.6 +/- 2.1; colitis: 1.8 +/- 0.8). Surprisingly, CF-MS showed only minor differences between colitis and healthy controls (healthy: 1.9 +/- 0.8; colitis: 2.3 +/- 0.4). In contrary, the intra-tissue concentrations of CF of the various formulations in colitis showed lower levels than the comparable healthy group after oral drug administration. Pharmacokinetic outcome was largely disease-dependent, while CF-MS confirmed their ability to local drug delivery. (C) 2010 Elsevier B.V. All rights reserved.