EMBRYOTOXICITY OF FREE AND LIPOSOME-ENCAPSULATED TAXOL IN THE CHICK

Taxol, an inhibitor of microtubule disaggregation, is used in the ther apy of breast, ovarian, and other human malignancies. The toxicity of taxol administration is due in part to the polyoxyethylated castor oil (Cremaphor(R)) Vehicle in which it is administered; taxol embryotoxic ity appears also to be partially attributable to vehicle toxicity. Lip osome encapsulation is a novel vehicle for drug administration. The ad ministration of taxol encapsulated in liposomes was evaluated in the c hick embryo. Albumen injections of taxol doses up to 30 mu g/egg were used to characterize dose-response curves for free and liposome-encaps ulated taxol, compared to liposome-only and saline-injected control eg gs. Sixty percent embryotoxicity (death or malformation) occurred with taxol doses of 1.5 mu g/egg. A 20-fold higher dose was necessary to p roduce the same degree of toxicity with liposome-encapsulated taxol. C urve-fitting equations were used to estimate median effective doses (E D(50)s) and slope functions of the dose response curves. The ED(50) fo r taxol was more than an order of magnitude lower than that for liposo me-encapsulated taxol. Estimated slope functions for the two dosage fo rms of taxol were the same, suggesting similar mechanisms of toxicity. The toxicity of liposomes alone was low.