Cancer chemotherapy is widely used and new and more potent antineoplastic drugs are being continually developed. In preclinical toxicological studies and in clinical trials of such new drugs, the national cancer institute utilizes intravenous route as the primary mode of drug administration. Most of the drugs have adequate inherent aqueous solubility and stability for intravenous delivery; for drugs having low solubility, existing solubilization techniques are used to increase the solubility. However, there are several drugs that are clinically very promising but are unavailable to clinicians because they cannot be properly formulated. The goal of phase i of this program is to demonstrate the utility of a novel prodrug design approach to solving the solubility/stability problems associated with such problematic drugs. We will develop stable aqueous formulations using novel micellar prodrugs of n-trifluoroacetyl adriamycin. The results of phase i studies will be utilized for the phase ii studies in which we will optimize the structure of the promoiety incorporating into the prodrug(s) those structural features necessary for adequate in vivo lability and safety leading to the development of commercially viable product(s). We will further explore the utility of our prodrug design approach to solve the solubility/stability problems of one or two other anticancer drugs of
