Size-dependent bioadhesion of micro- and nanoparticulate carriers to the inflamed colonic mucosa.
OBJECTIVE
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 trinitrobenzenesulfonic acid. Fluorescent polystyrene particles with a size of 0.1, 1, or 10 microm 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-micorm 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-microm 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.
Lamprecht
A
A
Department of Biopharmacy and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany. alla0004@stud.uni-sb.de
Schäfer
U
U
Lehr
C M
CM
D000269:Adhesives / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D002214:Capsules / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003092:Colitis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004337:Drug Carriers / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology*; D010316:Particle Size; D051381:Rats; D011917:Rats, Inbred Lew
D000269:Adhesives; D002214:Capsules; D004337:Drug Carriers