A GLUCOSE-MEDIATED POLYMERIC INSULIN DELIVERY SYSTEM

THE OBJECTIVE OF THIS PROJECT IS TO DEFINE THE OPTIMAL PARAMETERS FOR AN ENZYMATICALLY CONTROLLED POLYMERIC INSULINDELIVERY SYSTEM. IN THIS SYSTEM, GLUCOSE OXIDASE IS IMMOBILIZED TO SEPHAROSE BEADS OR TO THE POLYMER BACKBONE OF THE INSULIN DELIVERY MATRIX. LYOPHILIZED INSULIN IS INCORPORATED INTO THE POLYMER MATRIX. THE RELEASE OF INSULIN IS CONTROLLED BY ITS DISSOLUTION AND DIFFUSION RATE. PRELIMINARY EXPERIMENTS HAVE SHOWN THAT INCREASING THE INSULIN DISSOLUTION RATE RESULTS IN AN INCREASED INSULIN RELEASE RATE FROM THE MATRIX. THIS CHANGE IN INSULIN DISSOLUTION RATE CAN BE CONTROLLED BY ALTERING THE PH OF THEMICROENVIRONMENT OF THE MATRIX. THIS PH CHANGE CAN BE MEDIATED BY THE CONVERSION OF GLUCOSE TO GLUCONIC ACID BY THE IMMOBILIZED GLUCOSE OXIDASE. WHEN GLUCOSE CONCENTRATIONS RISE, THE ENZYME CATALYZES THE PRODUCTION OF GLUCONIC ACID AND LOWERS THE MICROENVIRONMENTAL PH OF THE MATRIX. THE LOWER PH RESULTS IN INCREASED INSULIN DISSOLUTION AND DIFFUSION FROM THE SYSTEM IN RESPONSE TO CHANGES IN GLUCOSE CONCENTRATION. THE ADVANTAGES TO THE DIABETIC OF AN INSULIN DELIVERY SYSTEMTHAT MORE CLOSELY MIMICS PHYSIOLOGIC INSULIN DELIVERY INCLUDE IMPROVED PATIENT COMPLIANCE AND IMPROVED SHORT- AND LONG-TERM THERAPY. THIS ENZYME-MEDIATED, FEEDBACK-CONTROLLED DELIVERY SYSTEM COULD BE APPLIED TO THE NUMEROUS NEW THERAPEUTIC PROTEINS NOW BEING DEVELOPED.