An oral drug delivery system targeting immune-regulating cells amelioratesmucosal injury in trinitrobenzene sulfonic acid-induced colitis

Control of immune-regulating cells in the colonic mucosa is important in th e treatment of patients with inflammatory bowel disease (IBD). The aim of s tudy was to examine the therapeutic effect of dexamethasone (DX) microspher es on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in rats, a model for human Crohn's disease. DX microspheres and DX alone were adminis tered orally to rats with TNBS-induced colitis. The macroscopic score. hist ological score, myeloperoxidase (MPO) activity, nitric oxide (NO) productio n, and gene expressions of proinflammatory cytokines, cyclooxygenase (COX)- 1, and COX-2 in the colonic tissue were determined. Proliferating cell nucl ear antigen (PCNA) staining and expression of nuclear transcription factor (NF)-kappaB in colonic tissues were also investigated. Macroscopic score, h istological score, MPO activity, and NO production in rats treated with DX microspheres were significantly lower than in those treated with DX alone. The gene expression of proinflammatory cytokines and COX-2 in rats treated with DX microspheres was down-regulated, compared with that in rats treated with DX alone. The number of PCNA-positive cells in the DX microsphere gro up was larger than in the group treated with DX alone. DX microspheres supp ressed NF-kappaB activation in TNBS-induced colitis more strongly than DX a lone. Oral administration of DX microspheres appears to ameliorate mucosal injury in TNBS-induced colitis, This drug delivery system could be an ideal therapy for human IBD.