The overall objective of this study is to provide a new drug delivery system and to enhance the solubility of existing compounds which exhibit excellent antitumor properties but are insoluble in water. Aqueous' solubility is essential for iv administration of antitumor drugs. Phase I research will solubilize diammineplatinumhydroxymalonate, 2, and (trans-1,2-diaminocyclohexane)platinumhydroxymalonate,2, complexes by conjugating them to hydrophilic and biodegradable polymeric ligand, carboxydextran; and to monomeric glucopyranose ligand. Complexes 1 and 2 were selected for solubilization studies because they are sparingly soluble but stable in aqueous solution, and exhibit different spectra of antitumor activity than cisplatin. Conjugation of these complexes to carboxydextran may provide a mechanism for the sustained delivery of antitumor agents. The merits of conjugating polymeric or monomeric ligands will be assessed from the antitumor data of the conjugates. Initial screening of the new conjugates will be done against L1210. Tumor will be injected ip and the treatment will be iv. Selected candidates will also be screened against a panel of solid tumors. Preliminary nephrotoxicity and hepatotoxicity studies will also be undertaken. The success of this program will provide expanded use of platinum complexes in cancer chemotherapy and this approach will be extended to the solubilization of other insoluble antitumor platinum and organic drugs in Phase II research.
