Title:Design and Development of Novel Azo Prodrugs using Various Permutations and Combinations of 5- and 4-Aminosalicylic Acids for Inflammatory Bowel Disease: A Colon-Targeted Approach
Volume: 12
Issue: 5
Author(s): Dhaneshwar Suneela, Vadnerkar Gaurav and Rai Himanshu
Affiliation:
Keywords:
4-Aminosalicylic acid, 5-Aminosalicylic acid, azo prodrug, colon-targeting, inflammatory bowel disease,
sulfasalazine.
Abstract: Novel carrier-linked azo prodrugs of 4 and 5-aminosalicylic acids (4-ASA and 5-ASA respectively) using the
same drugs as carriers in different permutations and combinations were designed for targeting colon affected with
inflammatory bowel disease (IBD). Improved hydrophilic nature of the prodrugs assisted in minimizing their absorption
in upper GIT and efficient delivery of the active drugs to colon as evidenced from their stability in aqueous buffers (pH
1.2 and 7.4) and upper GIT homogenates with 68-91% release on incubation with rat cecal matter. Amongst the series,
4A4AAZ (prodrug of 4-ASA with 4-ASA) at a dose of 53 mg/Kg was found to be the most promising candidate as it
substantially alleviated the quantifying markers of colonic inflammation in TNBS-induced experimental colitis in Wistar
rats. Moreover it displayed significantly lower GI toxicity (at ten times higher dose). 5-ASA- induced pancreatitis and
sulfapyridine-induced adverse effects on liver that are characteristic of sulfasalazine were not observed with 4A4AAZ. It
could be explored further as a potential candidate for IBD patients intolerant to pancreatitis induced by oral administration
of 5-ASA.
