title: Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid with D-phenylalanine for colon specific drug delivery in inflammatory bowel disease.
abstract: Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) only 15% release was observed over a period of 7h. In rat fecal matter the release of 5-aminosalicylic acid was almost complete (85%), with a half-life of 160.1 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid.
authors.affiliation: Department of Pharmaceutical Chemistry, Bharati Vidyapeeth University, Poona College of Pharmacy, Pune 411038, Maharashtra, India. suneeladhaneshwar@rediffmail.com
authors.forename: Suneela S
authors.initials: SS
authors.lastname: Dhaneshwar
authors.forename: Neha
authors.initials: N
authors.lastname: Gairola
authors.forename: Mini
authors.initials: M
authors.lastname: Kandpal
authors.forename: Lokesh
authors.initials: L
authors.lastname: Bhatt
authors.forename: Gaurav
authors.initials: G
authors.lastname: Vadnerkar
authors.forename: S S
authors.initials: SS
authors.lastname: Kadam
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003106:Colon / Q000473:pathology; D016503:Drug Delivery Systems; D015195:Drug Design; D006851:Hydrochloric Acid / Q000737:chemistry; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D007700:Kinetics; D019804:Mesalamine / Q000138:chemical synthesis* / Q000494:pharmacology; D008956:Models, Chemical; D008968:Molecular Conformation; D010649:Phenylalanine / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D012460:Sulfasalazine / Q000737:chemistry
chemical_list: D011355:Prodrugs; D012460:Sulfasalazine; D010649:Phenylalanine; D019804:Mesalamine; D006851:Hydrochloric Acid