Induction of oxidative stress by Taxol® vehicle Cremophor-EL triggers production of interleukin-8 by peripheral blood mononuclear cells through the mechanism not requiring de novo synthesis of mRNA.
Induction of oxidative stress by Taxol® vehicle Cremophor-EL triggers production of interleukin-8 by peripheral blood mononuclear cells through the mechanism not requiring de novo synthesis of mRNA.
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DOI：
10.1016/j.nano.2015.07.012
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发表时间：
2015-11
期刊：
影响因子：
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通讯作者：
Dobrovolskaia MA
中科院分区：
文献类型：
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作者：
Ilinskaya AN;Clogston JD;McNeil SE;Dobrovolskaia MA
了解细胞毒性肿瘤药物及其载体和制剂辅料诱导促炎反应的能力对于建立安全有效的制剂非常重要。有关紫杉醇传统制剂Taxol®诱导细胞因子反应的文献数据存在争议，而这种药物的纳米白蛋白制剂Abraxane®的促炎作用没有数据可用。在此，我们展示并解释了Taxol®和Abraxane®在细胞因子诱导谱上的差异，并描述了纳米辅料Cremophor EL诱导细胞因子的新机制，这种纳米辅料并非Taxol®独有的，通常用于制药行业的各种小分子药物的输送。紫杉醇载体Cremophor-EL通过旁路基因表达的机制诱导人外周血细胞产生IL-8。Cremophor-EL诱导的ROS激活MAPK p38，使预先合成的IL-8 mRNA稳定，并由其产生蛋白。
Understanding the ability of cytotoxic oncology drugs, and their carriers and formulation excipients, to induce pro-inflammatory responses is important for establishing safe and efficacious formulations. Literature data about cytokine response induction by the traditional formulation of paclitaxel, Taxol®, is controversial, and no data is available about the pro-inflammatory profile of the nano-albumin formulation of this drug, Abraxane®. Herein, we demonstrate and explain the difference in the cytokine induction profile between Taxol® and Abraxane®, and describe a novel mechanism of cytokine induction by a nanosized excipient, Cremophor EL, which is not unique to Taxol® and is commonly used in the pharmaceutical industry for delivery of a wide variety of small molecular drugs. Taxol vehicle Cremophor-EL induces interleukin-8 (IL-8) in human peripheral blood cells through the mechanism bypassing gene expression. Reactive Oxygen Species (ROS) induced by Cremophor-EL activate MAPK p38, which results in stabilization of pre-synthesized IL-8 mRNA and production of the protein from this mRNA.