title: Colonic delivery of carboxyfluorescein by pH-sensitive microspheres in experimental colitis.
abstract: 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® 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 μg/mlh), 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.
authors.affiliation: Laboratory of Pharmaceutical Engineering, University Franche-Comté, Besançon, France.
authors.forename: Desiree
authors.initials: D
authors.lastname: Kietzmann
authors.forename: Brice
authors.initials: B
authors.lastname: Moulari
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: D000284:Administration, Oral; D000285:Administration, Rectal; D000818:Animals; D001682:Biological Availability; D003092:Colitis / Q000473:pathology*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005452:Fluoresceins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008297:Male; D008863:Microspheres; D011109:Polymethacrylic Acids / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014302:Trinitrobenzenesulfonic Acid
chemical_list: D005452:Fluoresceins; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; C024098:6-carboxyfluorescein; D014302:Trinitrobenzenesulfonic Acid