Approaches and opportunities in colon-specific drug delivery.

With the determination of the exact mode of action of sulfasalazine 20 years ago, attention and interest was drawn to the colonic delivery of drugs. A few years before that it became clear that some orally administered laxative drugs are active only after arrival at the large intestine. This resulted in research activity that led to the development of colonic dosage forms. Two major approaches were reported: (1) protective coats that bring the dosage form as close as possible to the colon after oral administration, (2) prodrugs, polymeric prodrugs, and biodegradable polymers that are degraded mostly by the unique enzymes of the colon. Usually, these enzymes are related to the normal colonic microflora. The new drug carriers were examined in vitro and in vivo (laboratory animals). Recently, an increasing number of studies suggest the use of polysaccharide hydrogels for oral delivery of colon-specific drug carriers. Colonic delivery of drugs is associated with the local delivery of salicylate derivatives to the large intestine for the topical treatment of ulcerative colitis and sometimes the local treatment of irritable bowel syndrome. A common belief is that colonic delivery for orally administered protein drugs is possible because of the postulated low proteolysis activity in the large intestine, an assumption that requires further verification. Yet, other opportunities for colonic delivery of drugs also exist. Some recent examples include bypassing small intestine metabolism, achieving constant absorption rates for some molecules, and delivering cationized antioxidant enzymes to the colonic epithelium. This article reviews the surge of research activity in the new area of colon-specific drug delivery systems and suggests some possible therapeutic opportunities in this field.