Sharma A, Sharma U S, Straubinger R M
Department of Pharmaceutics, University at Buffalo, State University of New York, Amherst 14260-1200, USA.
Cancer Lett. 1996 Oct 22;107(2):265-72. doi: 10.1016/0304-3835(96)04380-7.
Paclitaxel, a recently approved antineoplastic agent, is cleared slowly from the peritoneal cavity after i.p. injection, and therefore appears to be promising for intracavitary therapy of malignancies confined to the peritoneal cavity. However the dose-limiting toxicity of Taxol, the clinical formulation of paclitaxel, was severe abdominal pain, likely caused by the excipients (Cremophor EL and ethanol) that are required to overcome low drug solubility. We tested the hypothesis that a liposome-based formulation could modulate paclitaxel toxicity independent of antitumor activity. The dose-dependence of toxicity and antitumor effect of paclitaxel liposomes was evaluated after i.p. administration against i.p. P388 leukemia. Liposomal paclitaxel showed antitumor activity similar to that of free paclitaxel (as Taxol), but was better tolerated by both healthy and tumor-bearing mice.
紫杉醇是一种最近获批的抗肿瘤药物，腹腔注射后从腹腔清除缓慢，因此对于局限于腹腔的恶性肿瘤腔内治疗似乎很有前景。然而，紫杉醇的临床制剂泰素的剂量限制性毒性是严重腹痛，这可能是由克服药物低溶解度所需的辅料（聚氧乙烯蓖麻油和乙醇）引起的。我们测试了这样一个假设，即基于脂质体的制剂可以在不依赖抗肿瘤活性的情况下调节紫杉醇的毒性。腹腔注射紫杉醇脂质体后，评估其对腹腔P388白血病的毒性和抗肿瘤作用的剂量依赖性。脂质体紫杉醇显示出与游离紫杉醇（作为泰素）相似的抗肿瘤活性，但健康小鼠和荷瘤小鼠对其耐受性更好。
