title: Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester, a polymeric colon-specific prodrug releasing 5-aminosalicylic acid and benzocaine, ameliorates TNBS-induced rat colitis.
abstract: Local anesthetics have beneficial effects on colitis. Dextran-5-(4-ethoxycarbonylphenylazo)salicylic acid ester (Dex-5-ESA), designed as a polymeric colon-specific prodrug liberating 5-ASA and benzocaine in the large intestine, was prepared and its therapeutic activity against colitis was evaluated using a TNBS-induced rat colitis model. Dex-5-ESA liberated 5-ASA and benzocaine in the cecal contents while (bio)chemically stable in the small intestinal contents and mucosa. Oral administration of Dex-5-ESA (equivalent to 10 mg 5-ASA/kg, twice a day) alleviated colonic injury and reduced MPO activity in the inflamed colon. In parallel, pro-inflammatory mediators, COX-2, iNOS and CINC-3, elevated by TNBS-induced colitis, were substantially diminished in the inflamed colon. Dex-5-ESA was much more effective for the treatment of colitis than 5-(4-ethoxycarbonylphenylazo)salicylic acid (5-ESA) that may not deliver benzocaine to the large intestine. Our data suggest that Dex-5-ESA is a polymeric colon-specific prodrug, liberating 5-ASA and benzocaine in the target site (large intestine), probably exerting anti-colitic effects by combined action of 5-ASA and benzocaine.
authors.affiliation: a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
authors.forename: Joon
authors.initials: J
authors.lastname: Nam
authors.affiliation: a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
authors.forename: Wooseong
authors.initials: W
authors.lastname: Kim
authors.affiliation: a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
authors.forename: Seongkeun
authors.initials: S
authors.lastname: Jeong
authors.affiliation: a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
authors.forename: Jin-Wook
authors.initials: JW
authors.lastname: Yoo
authors.affiliation: a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: a College of Pharmacy, Pusan National University , Busan , Republic of Korea.
authors.forename: Yunjin
authors.initials: Y
authors.lastname: Jung
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001566:Benzocaine / Q000494:pharmacology*; D002432:Cecum / Q000187:drug effects / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D003911:Dextrans / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D019804:Mesalamine / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology*; D011355:Prodrugs / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology
chemical_list: D003911:Dextrans; D018836:Inflammation Mediators; D011108:Polymers; D011355:Prodrugs; D019804:Mesalamine; D014302:Trinitrobenzenesulfonic Acid; D001566:Benzocaine
keywords: 5-Aminosalicylic acid; benzocaine; colitis and dextran; colon-specific prodrug