Antitumor Effect of Taxol-containing Liposomes in a Taxol-resistant Murine Tumor Model1

Taxol is a promising agent for use in ovarian cancer and other malig nancies. One problem associated with taxol is 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 taxolresistant 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 £30mg/kg per injection (the maximum tolerated dose). In contrast, taxol-liposomes were well tolerated at doses greater than or equal to the maximum toler ated dose of free taxol and showed significant tumor growth inhibition at 10-45 mg/kg per injection.