Paclitaxel-liposomes for intracavitary therapy of intraperitoneal P388 leukemia
Paclitaxel-liposomes for intracavitary therapy of intraperitoneal P388 leukemia
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DOI：
10.1016/0304-3835(96)04380-7
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发表时间：
1996-10-22
期刊：
影响因子：
9.7
通讯作者：
Straubinger, RM
中科院分区：
文献类型：
--
作者：
Sharma, A;Sharma, US;Straubinger, RM
紫杉醇是最近批准的抗肿瘤药物，腹膜内注射后会从腹膜腔缓慢清除，因此似乎有望用于腹膜腔内恶性肿瘤的腔内治疗。然而，紫杉醇的临床制剂Taxol(R) 的剂量限制性毒性是严重腹痛，这可能是由克服低药物溶解度所需的赋形剂（Cremophor EL(R) 和乙醇）引起的。我们测试了基于脂质体的制剂可以独立于抗肿瘤活性调节紫杉醇毒性的假设。紫杉醇脂质体IP给药后对IP P388白血病的毒性和抗肿瘤作用的剂量依赖性进行了评估。脂质体紫杉醇表现出与游离紫杉醇（Taxol(R)）相似的抗肿瘤活性，但健康小鼠和荷瘤小鼠的耐受性更好。
Paclitaxel, a recently approved antineoplastic agent, is cleared slowly from the peritoneal cavity after IP injection, and therefore appears to be promising for intracavitary therapy of malignancies confined to the peritoneal cavity. However the dose-limiting toxicity of Taxol(R), the clinical formulation of paclitaxel, was severe abdominal pain, likely caused by the excipients (Cremophor EL(R) 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 IP administration against IP P388 leukemia. Liposomal paclitaxel showed antitumor activity similar to that of free paclitaxel (as Taxol(R)), but was better tolerated by both healthy and tumor-bearing mice.