DEVELOPMENT OF NEW LIPOPHILIC CISPLATIN ANALOGUES

New lipophilic cis-platinum analogues that are non-nephrotoxic and have a broader spectrum of antitumor activity will be synthesized and formulated entrapped in liposomes of different composition and size. The toxicity, pharmacology, tumor uptake, cellular effect and antitumor activity of a few prototype liposomal-platinum preparations will be studied and compared with those of cis-platinum, the most promising second and third generation platinum complexes, and the non-entrapped compounds. The evaluation of liposomal-platinum for the targeted therapy of liver and lung metastases will receive particular attention. The cellular mechanisms involved in the increased cytotoxicity of liposomal-platinum will be studies in human cell lines sensitive and resistant to platinum derivatives. The study will define the potential clinical application of liposomes as carriers of platinum complexes and will result in the development of liposomal-platinum preparations for clinical use. The information generated will be essential in improving the design and use of drug carriers for antitumor agents.