Ovarian cancer has one of the highest death rates of any gynecological cancers despite the fact that it rarely disseminates from the peritoneal cavity. A major cause of deaths is the inability to control the disease within the peritoneal cavity. Pharmacokinetic modelling studies have suggested a major pharmacokinetic advantage of intraperitoneally (IP) administered drugs to an IP tumor. Binding of anticancer drugs to water soluble polymeric carriers results in the decrease of their peritoneal permeability and sustained exposure of tumor cells to high concentrations of cytotoxic agents with, presumably, lower toxicity. Sustained intracellular release of anticancer drugs (adriamycin and chlorin e6) and the targeting potential of N-(2-hydroxypropoly)methacrylamide (HPMA) copolymers provide the rationale for this proposal. A new drug delivery system is proposed which contains two drugs, adriamycin and chlorin e6 and a monoclonal antibody (OV-TL 3) that recognizes a common antigen both on a human ovarian cancer model (OVCAR-3) and on human ovarian tumors of different types. Our preliminary results have shown: a)lower toxicity of polymer bound anticancer drugs (including adriamycin and chlorin e6) when compared to free (unbound) drugs b)targetability of HPMA copolymer-anticancer drug conjugates c)decreased peritoneal permeability of drug carriers based on HPMA copolymers d)considerably increased antitumor activity of combined chemotherapy and photodynamic therapy in the treatment of C1300 neuroblastoma. Only a combination of HPMA copolymer bound adriamycin with an HPMA copolymer bound chlorin e6 produced long term survivors in this model. Based on these results a new targetable polymeric drug delivery system for the simultaneous delivery of adriamycin and chlorin e6 is proposed. A detailed evaluation of the physicochemical and biological properties as well as of the antitumor activity of these new polymeric drugs on a human ovarian cancer model is planned. The results obtained will provide a new therapeutic method for the treatment of human ovarian cancer.
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