Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa

Purpose. The size-dependent deposition of microparticles and nanoparticles after oral administration to rats using an experimental model colitis was examined. Local delivery of an entrapped drug could reduce side effects and would be a distinct improvement compared with existing colon delivery devices. Methods. Ulcerative colitis was induced in Lewis rats with trinitro-benzenesulfonic acid. Fluorescent polystyrene particles with a size of 0.1, 1, or 10 mum were administered for 3 days. The animals then were sacrificed and their guts resected; Particle distribution in the colon was imaged by confocal laser scanning microscopy and quantified by fluorescence spectrophotometry. Results. In the inflamed tissue, an increased adherence of particles was observed at the thicker mucus layer and in the ulcerated regions. A size dependency of the deposition was found, and an increased number of attached particles to the colon was determined compared with the control group. For 10-mum particles, only fair deposition was observed (control group: 1.4 +/-: 0.6%; colitis: 5.2 +/- 3.8% of administered particle mass). One-micrometer particles showed higher binding (control group: 2.0 +/- 0.8%; colitis: 9.1 +/- 4.2%). Highest binding was found for 0.1-mum particles (control group: 2.2 +/- 1.6%; colitis:14.5 +/- 6.3%). The ratio of colitis/control deposition increased with smaller particle sizes. Conclusions The use of submicron-sized carriers holds promise for the targeted delivery of drugs to the inflamed colonic mucosal areas in inflammatory bowel disease.