Scialli A R, DeSesso J M, Rahman A, Husain S R, Goeringer G C
Department of Obstetrics and Gynecology, Georgetown University Medical Center, Washington, D.C. 20007-2197, USA.
Pharmacology. 1995 Sep;51(3):145-51. doi: 10.1159/000139328.
Taxol, an inhibitor of microtubule disaggregation, is used in the therapy of breast, ovarian, and other human malignancies. The toxicity of taxol administration is due in part to the polyoxyethylated castor oil (Cremaphor) vehicle in which it is administered; taxol embryotoxicity appears also to be partially attributable to vehicle toxicity. Liposome encapsulation is a novel vehicle for drug administration. The administration of taxol encapsulated in liposomes was evaluated in the chick embryo. Albumen injections of taxol doses up to 30 micrograms/egg were used to characterize dose-response curves for free and liposome-encapsulated taxol, compared to liposome-only and saline-injected control eggs. Sixty percent embryotoxicity (death or malformation) occurred with taxol doses of 1.5 micrograms/egg. A 20-fold higher dose was necessary to produce the same degree of toxicity with liposome-encapsulated taxol. Curve-fitting equations were used to estimate median effective doses (ED50s) and slope functions of the dose response curves. The ED50 for taxol was more than an order of magnitude lower than that for liposome-encapsulated taxol. Estimated slope functions for the two dosage forms of taxol were the same, suggesting similar mechanisms of toxicity. The toxicity of liposomes alone was low.
紫杉醇是一种微管解聚抑制剂，用于治疗乳腺癌、卵巢癌及其他人类恶性肿瘤。紫杉醇给药的毒性部分归因于其所用的聚氧乙烯蓖麻油（克列莫佛）载体；紫杉醇的胚胎毒性似乎也部分归因于载体毒性。脂质体包裹是一种新型的给药载体。在鸡胚中评估了脂质体包裹的紫杉醇的给药情况。与仅注射脂质体和注射生理盐水的对照蛋相比，用白蛋白注射高达30微克/蛋剂量的紫杉醇来描绘游离和脂质体包裹的紫杉醇的剂量反应曲线。当紫杉醇剂量为1.5微克/蛋时，出现60%的胚胎毒性（死亡或畸形）。对于脂质体包裹的紫杉醇，需要高出20倍的剂量才能产生相同程度的毒性。使用曲线拟合方程来估计半数有效剂量（ED50）和剂量反应曲线的斜率函数。紫杉醇的ED50比脂质体包裹的紫杉醇低一个数量级以上。两种剂型紫杉醇的估计斜率函数相同，表明毒性机制相似。单独脂质体的毒性较低。
