Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing docetaxel
Preparation, characterization, cytotoxicity and pharmacokinetics of liposomes containing docetaxel
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DOI：
10.1016/s0168-3659(03)00271-2
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发表时间：
2003-09-04
影响因子：
10.8
通讯作者：
Cattel, L
中科院分区：
文献类型：
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作者：
Immordino, ML;Brusa, P;Cattel, L
紫杉烷类，紫杉醇和多西他赛，是临床试验中用于对抗卵巢癌、乳腺癌、肺癌和头颈癌的抗癌剂。Paclitazone在水中非常不溶，通常使用Cremophor EL配制，Doceetazone在水中更易溶，使用Tween 80和乙醇配制。吐温80虽然比Cremophor EL毒性小，但可能是造成某些毒性作用的原因。为了消除这些媒介物并提高药物的抗肿瘤功效，紫杉烷已被掺入脂质体中。我们比较了多西他赛在常规脂质体和聚乙二醇化脂质体中的处方、稳定性、生物分布和药代动力学。在检查的几种制剂中，由ePC/PG/ CHOL 9：1：2和ePC/PG/DSPE-PEG（2000）/CHOL 9：1：2：0.7组成的紫杉醇-脂质体最有效。常规的和PEG化的紫杉醇脂质体在4 ℃下15天后都是稳定的，而在37 ℃下存在血清时，它们不太稳定。在HT-29和Igrovl细胞系上评价的紫杉醇-脂质体的IC 50值保持非常高。静脉注射[C-14]多西他赛（配制于吐温80或H-3标记的常规或聚乙二醇化脂质体中）后，在Balb/c小鼠中评价了药代动力学和生物分布。多西他赛的t（1/2 β）较低（52.3 min），常规多西他赛-脂质体的t（1/2 β）升高至260 min，聚乙二醇化多西他赛脂质体升高至665 min。生物分布研究证实了药代动力学。(C)2003年由Elsevier B. V.出版
The taxanes, paclitaxel and docetaxel, are anticancer agents used in clinical trials against ovarian carcinoma, breast, lung and head/neck cancer. Paclitaxel, very insoluble in water, is generally formulated using Cremophor EL, Docetaxel, more soluble in water, is formulated using Tween 80 and ethanol. Tween 80, albeit less toxic than Cremophor EL, may be responsible of some toxic effects. To eliminate these vehicles and improve the drug's antitumor efficacy, taxanes have been incorporated in liposomes. We compared formulation, stability, biodistribution and pharmacokinetics of docetaxel in conventional and PEGylated liposomes. Of the several formulations examined, docetaxel-liposomes composed of ePC/PG/ CHOL 9:1:2 and ePC/PG/DSPE-PEG(2000)/CHOL 9:1:2:0.7 were the most effective. Both conventional and PEGylated docetaxel-liposomes were stable at 4degreesC after 15 days, whereas in the presence of serum at 37degreesC they were less stable. The IC50 values of docetaxel-liposomes, evaluated on HT-29 and Igrovl cell lines, remained very high. Pharmacokinetics and biodistribution were evaluated in Balb/c mice after i.v. injection of [C-14]docetaxel, formulated in Tween 80 or in H-3-labeled conventional or PEGylated liposomes. The t(1/2beta), which was low for docetaxel (52.3 min), rose to 260 min for conventional docetaxel-liposomes and to 665 min for PEGylated docetaxel liposomes. Biodistribution studies confirmed the pharmacokinetics. (C) 2003 Published by Elsevier B.V.