CATALYTIC FUNCTIONALIZATION OF POLYMERS - A NOVEL-APPROACH TO SITE-SPECIFIC DELIVERY OF MISOPROSTOL TO THE STOMACH

The application of functionalized polymers to site-directed delivery o f the antiulcer prostaglandin, misoprostol, is described. By use of ho mogeneous catalysis, the simple polymer, polybutadiene, was modified t o incorporate the specialized requirements for controlled delivery of misoprostol to the stomach. An acid labile silyl ether bond to the C-1 1 hydroxyl of misoprostol was installed as the primary rate determinin g step for drug release, and a series of analogs, in which the steric hindrance about the silicon atom was varied, was prepared and evaluate d for in vitro release rates, efficacy against indomethacin induced ga stric damage and diarrheagenic activity. The diisopropylsilyl analog, the slowest releasing system studied, showed efficacy equal to misopro stol against indomethacin-induced gastric damage and no diarrhea at th e highest dose tested.