COLON-SPECIFIC DRUG DELIVERY

The delivery of drugs to the colon has a number of important implications in the field of pharmacotherapy. Several diseases, including IBD, can be treated more effectively by local delivery of antiinflammatory agents to the large intestine. SASP is the classic prodrug used to deliver 5-ASA for localized chemotherapy of IBD. Due to adverse side-effects of SASP, a number of newer 5-ASA prodrugs are under development. The use of azo-reductase activity of colonic microflora has also been used to liberate 5-ASA from polymeric prodrugs and more recently to catalyze the partial degradation of hydrogels in the colon. These hydrogels may be useful in the delivery of peptides and proteins to the colon. The colonic bacteria also produce a wide array of glycosidases capable of hydrolyzing simple glycosides as well as polysaccharides. These enzymes have been exploited to release drugs in the large intestine. A number of studies have indicated that corticosteroids released from glycoside prodrugs are absorbed from the lumen of the large intestine and lead to much higher colonic tissue levels than are possible when the parent corticosteroid is administered systemically. The colon is also a potential site for absorption of peptides and proteins. Some potential limitations involved in oral peptide and protein delivery from the colon are discussed. In addition, the use of specific receptors and lectins on colonic mucosal cells offer the potential to deliver drugs to the colonic mucosa in a selective way. Interestingly, certain lectins have significantly increased binding to colonic mucin in several disease states: IBD and large bowel carcinoma. Exploiting these differences could lead to new, biologically oriented colonic drug delivery systems that deliver drugs selectively to the target cells, thereby reducing systemic exposure.