International journal of colorectal disease

Effectiveness of budesonide-succinate-dextran conjugate as a novel prodrug of budesonide against acetic acid-induced colitis in rats.

PMID 20669022


Anti-inflammatory drugs with high potency and low systemic adverse effects, such as budesonide, are drugs of choice for the treatment of ulcerative colitis (UC). Budesonide controlled-release formulations are now being used to induce and maintain clinical remission of Crohn's disease. Budesonide-dextran conjugates were synthesized as novel prodrugs of budesonide for oral controlled delivery of the major part of the drug to the colon without needing to coat the pellets of the drug. The aim of this study was to evaluate the in vivo efficacy of this conjugate against acetic acid-induced colitis in rats. Experimental UC was induced by rectal instillation of 4% solution of acetic acid to rats. After induction of colitis, rats were treated with vehicle (dextran solution), mesalasine (120 mg/kg), budesonide suspension (300 microg/kg) and BSD-70 (equivalent to 300 microg/kg of budesonide), prednisolon (4 mg/kg), hydrocortisone acetate enema (20 mg/kg), and 5-ASA enema (Asacol) (400 mg/kg) for 5 days and then colon macroscopic and microscopic sections were examined for inflammatory response. Vehicle-treated rats presented bloody diarrhoea and gross lesions. The effective formulations for attenuating the damage were BSD-70, oral prednisolon and hydrocortisone acetate enema. Rats treated with BSD-70 showed huge improvement in macroscopic and histological scores of colitis compared to the negative control group and mesalasine and budesonide suspension. Data indicated that budesonide-dextran conjugate is effective in improving signs of inflammation in experimental model of colitis through selective delivery of the drug to the inflamed area.