Delivery of glucocorticoid conjugate in rat gastrointestinal tract and itstreatment for ulcerative colitis

AIM: To evaluate colonic delivery and therapeutic effect of the newly synth esized dexamethasone (DX)-dextran (500 000) conjugate (DXD50) in the rat. M ETHODS: The amount of dexamethasone was measured in the contents from diffe rent parts of rat gastrointestinal tract,ate. Therapeutic effect of and in plasma after ig conjugate. Therapeutic effect of conjugate and DX was teste d in trinitrobenzenesulfonic acid-induced colitis in rat. Repair of colitis was assessed by measuring colonic ulceration area, colon weight, and colon ic myeloperoxidase (MPO) activity. Systemic immunosuppression of DX was eva luated with weight of thymus and spleen and lymphocyte count in peripheral blood from rat with ulcerative colitis. RESULTS: Dexamethasone released fro m conjugate was mainly distributed in contents of cecum. and colon. When DX D50 and DX 0.25 mu mol (.) kg(-1 .) d(-1) were used ig to treat ulcerative colitis in rat, the ulcerative area of colon was reduced by 55.6 % and 33.3 %, respectively whereas colon weight was reduced by 17.9 % and 2.6 %, resp ectively. The conjugate had no effect on lymphocyte count in peripheral blo od, spleen weight, and thymus weight of rat which could be reduced markedly by the same dose of DX (P < 0.05 vs control). CONCLUSION: DXD50, which cou ld specifically deliver DX to large intestine, is a promising agent in the treatment of human inflammatory bowel disease.