THE GOAL OF THIS PROJECT IS TO DEVELOP A METHOD FOR THE SELECTIVE DELIVERY OF ANTICANCER DRUGS TO LOCALLY HEATED TUMORS.

THE GOAL OF THIS PROJECT IS TO DEVELOP A METHOD FOR THE SELECTIVE DELIVERY OF ANTICANCER DRUGS TO LOCALLY HEATED TUMORS. THE THERAPEUTIC EFFECTIVENESS OF CANCER CHEMOTHERAPY CAN BE IMPROVED IF THE DRUG IS DELIVERED TO THE TUMOR REGION IN HIGH CONCENTRATION WHILE REDUCING THE AMOUNT DEPOSITED IN NORMAL TISSUES. THE USE OF TEMPERATURE-SENSITIVE LIPOSOMES FOR SELECTIVE DRUG DELIVERY HAS BEEN ESTABLISHED IN SMALL ANIMAL TUMOR MODELS. THE SPECIFIC AIMS OF THE PROPOSED PHASE I STUDY ARE DESIGNED TO EVALUATE, IMPROVE, AND EXTEND EXISTING TECHNIQUES FOR PRODUCING LOCAL TUMOR HYPERTHERMIA AND FOR FORMING TEMPERATURE-SENSITIVE LIPOSOMES SO THAT CLINICAL STUDIES OF THIS NEW METHOD OF DRUG TARGETING CAN BE PLANNED. THE RESULTS OF THE PHASE I STUDY WILL BE: 1.THE ESTABLISHMENT OF WELL-CHARACTERIZED METHODS FOR HEAT-SELECTIVE TARGETED DRUG RELEASE DURING LOCALIZED HYPERTHERMIA AND 2.AN APPARATUS FOR THE LARGE-SCALE PRODUCTION OF STABLE LIPOSOMES OF WELL-DEFINED SIZES, AND GOOD TEMPERATURE-SENSITIVE DRUG RELEASE CHARACTERISTICS. THE LIPOSOMES AND THE HYPERTHERMIA SYSTEM WILL BE COMBINED IN PHASE II STUDIES OF LOCAL ANTICANCER DRUG DELIVERY TO SOLID TUMORS IN LARGE ANIMALS. THE RESULTS OF THE PHASE II STUDIES WILL PROVIDE A BASIS FOR CLINICAL