Design and development of latentiated strategy for delivery of mesalazine to colon

Mesalazine is widely used systemically or topically to achieve and maintain remission in inflammatory bowel disease. Latentiated derivatives of mesalazine having L-histidine and L-tyrosine covalently linked via an amide linkage were designed, developed and screened in 2, 4, 6-trini-trobenzenesulphonic acid-induced experimental colitis in rats. Incubation of prodrugs with tissue homogenates of stomach and small intestine of rats furnished 4-8% and 9-12% release respectively over a 10-h period. Their colon-specific activation was confirmed from their release profile on incubation with rat fecal and cecal material at 37°C in anaerobic conditions (5% CO2). 79-98% release of mesalazine was observed in rat fecal matter while almost complete release of mesalazine (99%) was observed in rat cecal matter over a 10-h period. The half-lives of mesalazine prodrugs ranged between 236-295 min following zero order kinetics. The improving effect of latentiated derivatives on the symptoms of colitis induced by 2, 4, 6-trinitrobenzenesulphonic acid is comparable to sulfasalazine. Amongst the reported prodrugs, potential of SSDGV2 (latentiated derivative of mesalazine with L-histidine) can be explored further as a promising candidate for the safer management of inflammatory bowel disease.