Antitumor Effect of Taxol-containing Liposomes in a Taxol-resistant Murine Tumor Model

Taxol is a promising agent for use in ovarian cancer and other malignancies. One problem associated with taxolis its low aqueous solubility, requiring Cremophor EL (polyethoxylated castor oil) and ethanol as ex-cipients(Diluent 12); these agents cause serious adverse effects. Liposomes containing taxol and phospholipid (in a 1:33 mole ratio, respectively) were prepared from phosphatidylglycerol and phosphatidylcholine in a 1:9 mole ratio. Antitumor effect was evaluated against Colon-26, a taxol-resistant murine tumor. Given as 1, 4, or 9 injections, free taxol given i.v. in Diluent 12 was ineffective at delaying tumor growth at doses =30 mg/kg per injection (the maximum tolerated dose). In contrast, taxol-liposomes were well tolerated at doses greater than or equal to the maximum tolerated dose of free taxol and showed significant tumor growth inhibition at 10-45 mg/kg per injection.