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.
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.


BACKGROUND
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.
Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Anna N
AN
Ilinskaya
Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Jeffrey D
JD
Clogston
Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA.
Scott E
SE
McNeil
Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, USA. Electronic address: marina@mail.nih.gov.
Marina A
MA
Dobrovolskaia
D000068196:Albumin-Bound Paclitaxel / Q000009:adverse effects*; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002460:Cell Line; D005990:Glycerol / Q000009:adverse effects / Q000031:analogs & derivatives*; D006801:Humans; D016209:Interleukin-8 / Q000097:blood / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D017239:Paclitaxel / Q000009:adverse effects*; D014677:Pharmaceutical Vehicles / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000009:adverse effects*
D000068196:Albumin-Bound Paclitaxel; D000970:Antineoplastic Agents; C508606:CXCL8 protein, human; D016209:Interleukin-8; D014677:Pharmaceutical Vehicles; C022131:cremophor; D011092:Polyethylene Glycols; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol
Abraxane®; Cremophor-EL; Cytokines; Immunotoxicity; Interleukin 8; Oxidative stress; Paclitaxel; Taxol®