CONTROLLED-RELEASE IMPLANTS OF DISULFIRM METABOLITES

THE PRINCIPAL OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE TECHNICAL FEASIBILITY OF DEVELOPING A DRUG-RELEASING IMPLANTFOR TREATMENT OF ALCOHOLISM. SPECIFIC AIMS DURING PHASE I ARE TO DEVELOP PROTOTYPE IMPLANTS THAT RELEASE DISULFIRAM METABOLITES AND TO TEST THE EFFICACY OF THESE IMPLANTS IN RATS. THE PROTOTYPE IMPLANTS WILL BE MADE OF BIOERODIBLE POLYMERS THAT WILL BE DESIGNED TO BIOERODE FOLLOWING COMPLETE DRUG DELIVERY. THE METABOLITES HAVE BEEN DETERMINED TO BE MUCH MORE POTENT THAN DISULFIRAM, WHICH SHOULD ALLOW LOWER RELEASE RATES, SMALLER IMPLANTS, AND LONGER DURATIONS. DRUG RELEASE RATES AND DURATIONS FROM PROTOTYPE IMPLANTS WILL BE DETERMINED BOTH IN VITRO AND IN VIVO, AND ENZYME INHIBITION DUE TO THE IMPLANTS WILL BE DETERMINED IN RATS AS A PRELIMINARY MEASURE OF EFFICACY. IFTHIS APPROACH IS SUCCESSFUL, IT COULD GREATLY INCREASE BOTH EFFICACY AND PATIENT COMPLIANCE IN TREATMENT PROGRAMS FOR ALCOHOLISM. THE PRINCIPAL OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE TECHNICAL FEASIBILITY OF DEVELOPING A DRUG-RELEASING IMPLANTFOR TREATMENT OF ALCOHOLISM. SPECIFIC AIMS DURING PHASE I ARE TO DEVELOP PROTOTYPE IMPLANTS THAT RELEASE DISULFIRAM METABOLITES AND TO TEST THE EFFICACY OF THESE IMPLANTS IN RATS. THE PROTOTYPE IMPLANTS WILL BE MADE OF BIOERODIBLE POLYMERS THAT WILL BE DESIGNED TO BIOERODE FOLLOWING COMPLETE DRUG DELIVERY. THE METABOLITES HAVE BEEN DETERMINED TO BE MUCH MORE POTENT THAN DISULFIRAM, WHICH SHOULD ALLOW LOWER RELEASE RATES, SMALLER IMPLANTS, AND LONGER DURATIONS. DRUG RELEASE RATES AND DURATIONS FROM PROTOTYPE IMPLANTS WILL BE DETERMINED BOTH IN VITRO AND IN VIVO, AND ENZYME INHIBITION DUE TO THE IMPLANTS WILL BE DETERMINED IN RATS AS A PRELIMINARY MEASURE OF EFFICACY. IFTHIS APPROACH IS SUCCESSFUL, IT COULD GREATLY INCREASE BOTH EFFICACY AND PATIENT COMPLIANCE IN TREATMENT PROGRAMS FOR ALCOHOLISM.