LIPOSOMAL MITOXANTRONE FOR THE LOCAL TREATMENT OF PERITONEAL CARCINOMATOSIS INDUCED BY COLON-CANCER CELLS IN MICE

Since liposomes are slowly resorbed from serous cavities, they may con stitute a valuable tool for the treatment of peritoneal carcinomatosis . We prepared mitoxantrone (MXN)-liposomes with various lipid composit ions and checked their antitumoral activity on a peritoneal carcinomat osis induced by a colon cancer cell injection (1 x 10(5) C51 cells) in BALB/c mice. MXN entrapment in liposomes was rapid and stable due to its high lipophilicity. MXN carried in phosphatidylcholine: cholestero l (2:1; G-liposomes) displayed a reduced toxicity in mice compared to the free drug. When tested at a non-toxic dose (2 mg/kg), MXN entrappe d in G-liposomes proved to be as efficient as the free drug. At a high er MXN dose (3 mg/kg), both G-liposomes and ne:cholesterol:dipalmitoyl phosphatidylethanolamine (7:2:1) liposomes, loaded with MXN, significa ntly increased the life span of mice compared to the free drug and six other liposome formulations. Increase in the MXN therapeutic index, w hen used in the liposomal form, could then merit further clinical inve stigations in regard to patients with malignancies confined to serous cavities.