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

Department of Pharmaceutics, University at Buffalo, State University of New York, Amherst, New York 14260-1200 [A. S., E. M., R. M. S.], and Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York 14263 [R. M.]

Taxol is a promising agent for use in ovarian cancer and other malignancies. One problem associated with taxol is its low aqueous solubility, requiring Cremophor EL (polyethoxylated castor oil) and ethanol as excipients (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.

¹ Supported by Grant CA55251 from the National Cancer Institute, NIH.

² To whom requests for reprints should be addressed, at the Department of Pharmaceutics, 539 Cooke Hall, University at Buffalo, State University of New York, Amherst, NY 14260-1200. Internet address: rms@acsu.buffalo.edu.

Received 9/ 7/93. Accepted 11/ 2/93.

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