A colon-specific drug-delivery system based on drug glycosides and the glycosidases of colonic bacteria

摘要: Steroid glycosides and the unique glycosidase activity of colonic microflora form basis a new colon-specific drug-delivery system. Drug are hydrophilic and, thus, poorly absorbed from small intestine. Once such glycoside reaches colon it can be cleaved by bacterial glycosidases, releasing free drug to mucosa. This concept was illustrated with dexamethasone 21-beta-D-glucoside (1) prednisolone (2), two prodrugs that may useful in treating inflammatory bowel disease. Hydrolysis beta-glucosidase fecal homogenates vitro released steroids. Glucosides 1 2 were administered rats intragastrically determine when where steroids released. Unmodified (3) (4) also given compare absorption glucosides Both found reach rat lower intestine 4-5 h, they rapidly hydrolyzed, Delivery steroid 3 (via glucoside 1) more specific than 4 2): nearly 60% an oral dose reached cecum, whereas less 15% cecum. When orally, almost exclusively intestine: 1% each