Engels Frederike K, Mathot Ron A A, Verweij Jaap
Department of Medical Oncology, Erasmus MC, Daniel den Hoed Cancer Center, Groene Hilledijk 301, 3075 EA Rotterdam, The Netherlands.
Anticancer Drugs. 2007 Feb;18(2):95-103. doi: 10.1097/CAD.0b013e3280113338.
The anticancer drug docetaxel (Taxotere) is formulated in the nonionic surfactant polysorbate 80 (Tween 80). Early in the clinical development of docetaxel, it became clear that docetaxel administration is associated with the occurrence of unpredictable (acute) hypersensitivity reactions and cumulative fluid retention. These side-effects have been attributed, in part, to the presence of polysorbate 80 and have consequently initiated research focused on the development of a less-toxic, better-tolerated polysorbate 80-free formulation of docetaxel. More recently, there is an increasing interest in developing a (polysorbate 80-free) docetaxel formulation that selectively targets malignant tissue, thereby increasing efficacy while decreasing the occurrence of side-effects related to wide and nonspecific body distribution. This review aims to discuss the preclinical and clinical results of pharmaceutical strategies [PEGylated (immuno)liposomal docetaxel, docetaxel-fibrinogen-coated olive oil droplets, docetaxel encapsulated nanoparticle-aptamer bioconjugates, submicronic dispersion formulation] to develop an alternative, solvent-free, delivery form for docetaxel characterized by increased efficacy and decreased toxicity.
抗癌药物多西他赛（泰索帝）是以非离子表面活性剂聚山梨酯80（吐温80）配制而成。在多西他赛的临床开发早期，很明显多西他赛给药与不可预测的（急性）过敏反应和累积性液体潴留的发生有关。这些副作用部分归因于聚山梨酯80的存在，因此引发了相关研究，重点是开发一种毒性更小、耐受性更好的不含聚山梨酯80的多西他赛制剂。最近，人们越来越关注开发一种（不含聚山梨酯80）的多西他赛制剂，该制剂能选择性地靶向恶性组织，从而在提高疗效的同时减少与广泛和非特异性全身分布相关的副作用的发生。本综述旨在讨论药物策略[聚乙二醇化（免疫）脂质体多西他赛、多西他赛-纤维蛋白原包被的橄榄油滴、多西他赛包封的纳米颗粒-适配体生物共轭物、亚微米分散制剂]的临床前和临床结果，以开发一种替代的、无溶剂的多西他赛递送形式，其特点是疗效提高和毒性降低。
