W1267 Thiopurine-Induced Peripheral T Cells Apoptosis and Drug Response in Patients With Crohn's Disease

Abstract

The standard treatment of IBD involves the application of anti-inflammatory drugs. These drugs become systemically bioavailable and bear a potential of strong adverse effects. Thus, targeting the inflamed areas of the intestine can reduce adverse effects. Polymeric particles have turned out to be a promising tool for the targeted delivery of drugs. We aimed to investigate the distribution of fluoresceine-labelled nanoparticles (NP) and microparticles (MP) in the rectal mucosa of patients with IBD by use of CLE. Fluoresceinaminewas covalently bound to poly(L-lactide-co-glycolide) (PLGA). From this modified polymer, nanoparticles of approximately 300 nm size and microparticles of 3.5 μm size were prepared. After bowel preparation a 30 ml enema containing 10E9 MP or 10E13 NP, resp., has been applied to patients with rectal Crohns disease (CD) or ulcerative colitis (UC). After two hours endoscope based CLE has been performed to visualize nanoparticles in areas of different stages of inflammation. Biopsies have been obtained from IBD patients to evaluate mucosal transport processes in miniaturized Ussing chambers by confocal laser endoscopy. We examined 16 patients with IBD (8 patients with CD, 10 patients with (UC), 7 of whom received NP while 9 received MP. No particles have been visualized on intact mucosal surfaces. In areas of mild to moderate inflammation only minor amounts of particles were visible. In contrast, we observed a marked accumulation of MP rather than NP in ulcerous lesions. Preliminary results from Ussing chamber experiments suggest an influx of particles into the gut mucosa through epithelial lesions. Representative images are shown in fig. 1. This is the first study demonstrating mucosal accumulation of microparticles and nanoparticles in intestinal lesions of patients with IBD. Drug containing particles may have a great potential to target these lesions more specifically in order to maximize therapeutic efficacy and minimize potential side effects. CLE is a useful tool to investigate drug delivery to mucosal surfaces.