title: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran. varshosaz@pharm.mui.ac.ir
authors.forename: Jaleh
authors.initials: J
authors.lastname: Varshosaz
authors.forename: Jaber
authors.initials: J
authors.lastname: Emami
authors.forename: Afshin
authors.initials: A
authors.lastname: Fassihi
authors.forename: Naser
authors.initials: N
authors.lastname: Tavakoli
authors.forename: Mohsen
authors.initials: M
authors.lastname: Minaiyan
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Ahmadi
authors.forename: Parvin
authors.initials: P
authors.lastname: Mahzouni
authors.forename: Farid
authors.initials: F
authors.lastname: Dorkoosh
mesh_terms: D019342:Acetic Acid / Q000009:adverse effects; D000818:Animals; D000893:Anti-Inflammatory Agents; D019819:Budesonide / Q000008:administration & dosage* / Q000627:therapeutic use; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy*; D003911:Dextrans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000627:therapeutic use; D008297:Male; D011239:Prednisolone / Q000627:therapeutic use; D011355:Prodrugs / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D019802:Succinic Acid
chemical_list: D000893:Anti-Inflammatory Agents; D003911:Dextrans; D011355:Prodrugs; C021650:hydrocortisone acetate; D019819:Budesonide; D011239:Prednisolone; D019802:Succinic Acid; D019342:Acetic Acid; D006854:Hydrocortisone