Development and characterization of a novel Cremophor® EL free liposome-based paclitaxel (LEP-ETU) formulation
Development and characterization of a novel Cremophor® EL free liposome-based paclitaxel (LEP-ETU) formulation
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DOI：
10.1016/j.ejpb.2004.06.009
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发表时间：
2005-01-01
影响因子：
4.9
通讯作者：
Ahmad, I
中科院分区：
文献类型：
--
作者：
Zhang, JA;Anyarambhatla, G;Ahmad, I
yTaxol（R）是一种用于治疗卵巢癌、乳腺癌、非小细胞肺癌和艾滋病相关的卡波西肉瘤的上市产品。它是迄今为止市场上最有效的抗癌药物之一。然而，紫杉醇仅微溶于水，因此，静脉内给药取决于使用非离子表面活性剂EL（聚乙氧基化蓖麻油）以获得临床相关的浓缩溶液。不幸的是，Cremophor（R）EL增加了毒性，并导致某些个体的超敏反应。我们已经开发了一种充分表征的新型冻干脂质体基紫杉醇（LEP-ETU）制剂，该制剂无菌、稳定且易于使用。冻干前后脂质体的平均粒径约为150 nm，药物包封率大于90%。稳定性数据表明，冻干的LEP-ETU在2-8 ℃和25 ℃下物理和化学稳定至少12个月。此外，该制剂可稀释至约0.25 mg/ml而没有药物沉淀或粒度变化。在磷酸盐缓冲盐水（PBS，pH 7.4）中的体外药物释放研究表明，小于6%的包封紫杉醇在120小时后释放，表明药物在生理温度下是高度稳定的包封形式。(C)2004 Elsevier B. V.保留所有权利。
yTaxol(R) is a marketed product for the treatment of ovarian, breast, non-small cell lung cancer and AIDS-related Kaposi's Sarcoma. It is thus far one of the most effective anticancer drugs available on the market. However, paclitaxel is only sparingly soluble in water and therefore, intravenous administration depends on the use of the non-ionic surfactant Cremophore(R) EL (polyethoxylated castor oil) to achieve a clinically relevant concentrated solution. Unfortunately, Cremophor(R) EL increases toxicity and leads to hypersensitivity reactions in certain individuals. We have developed a well characterized novel lyophilized liposome-based paclitaxel (LEP-ETU) formulation that is sterile, stable and easy-to-use. The mean particle size of the liposomes is about 150 run before and after lyophilization, and the drug entrapment efficiency is greater than 90%. Stability data indicated that the lyophilized LEP-ETU was physically and chemically stable for at least 12 months at 2-8 and 25 degreesC. Moreover, the formulation can be diluted to about 0.25 mg/ml without drug precipitation or change in particle size. In vitro drug release study in phosphate-buffered saline (PBS, pH 7.4) showed that less than 6% of the entrapped paclitaxel was released after 120 h, indicating that the drug is highly stable in an entrapped form at physiologic temperature. (C) 2004 Elsevier B.V. All rights reserved.