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

Nanomedicine. 2015 Nov;11(8):1925-38. doi: 10.1016/j.nano.2015.07.012. Epub 2015 Aug 15.


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®, are controversial, and no data are 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.

From the clinical editor: Advances in nanotechnology have enabled the production of many nano-formulation drugs. The cellular response to drugs has been reported to be different between traditional and nano-formulations. In this article, the authors investigated and compared cytokine response induction profiles between Taxol® and Abraxane®. The findings here provided further understanding to create drugs with better safety profiles.

Keywords: Abraxane®; Cremophor-EL; Cytokines; Immunotoxicity; Interleukin 8; Oxidative stress; Paclitaxel; Taxol®.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albumin-Bound Paclitaxel / adverse effects*
  • Animals
  • Antineoplastic Agents / adverse effects*
  • Cell Line
  • Glycerol / adverse effects
  • Glycerol / analogs & derivatives*
  • Humans
  • Interleukin-8 / blood
  • Interleukin-8 / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Mice
  • Oxidative Stress / drug effects*
  • Paclitaxel / adverse effects*
  • Pharmaceutical Vehicles / adverse effects*
  • Polyethylene Glycols / adverse effects*


  • Albumin-Bound Paclitaxel
  • Antineoplastic Agents
  • CXCL8 protein, human
  • Interleukin-8
  • Pharmaceutical Vehicles
  • cremophor
  • Polyethylene Glycols
  • cremophor EL
  • Paclitaxel
  • Glycerol