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

Abstract

BACKGROUND:

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.

MATERIALS AND METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

• Authors: Jaleh Varshosaz, Jaber Emami, Afshin Fassihi, Naser Tavakoli, Mohsen Minaiyan, Fatemeh Ahmadi, Parvin Mahzouni, Farid Dorkoosh
• Journal: International journal of colorectal disease (Int J Colorectal Dis) Vol. 25 Issue 10 Pg. 1159-65 (Oct 2010) ISSN: 1432-1262 [Electronic] Germany
• PMID: 20669022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Dextrans
• Prodrugs
• hydrocortisone acetate
• Budesonide
• Prednisolone
• Succinic Acid
• Acetic Acid
• Hydrocortisone

Topics

• Acetic Acid (adverse effects)
• Animals
• Anti-Inflammatory Agents
• Budesonide (administration & dosage, therapeutic use)
• Colitis (chemically induced, drug therapy)
• Dextrans
• Hydrocortisone (analogs & derivatives, therapeutic use)
• Male
• Prednisolone (therapeutic use)
• Prodrugs (chemistry, therapeutic use)
• Rats
• Rats, Wistar
• Succinic Acid