Taxol®-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor® EL

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  • Pieter Vader, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, Holland
  • Marcel HAM Fens, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht & Childrens Hospital Oakland Research Institutet, Oakland, CA, USA, Danmark
  • Nikoleta Sachini, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, Holland
  • Birgitte A van Oirschot, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, Holland
  • Grietje Andringa, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, Holland
  • Antoine CG Egberts, Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, Holland
  • Carlo AJM Gaillard, Depertment of Nephrology, Vrije University Medical Center, Amsterdam, Holland
  • Jan Trige Rasmussen
  • Ricard van Wijk, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, Holland
  • Wouter W van Solinge, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, Holland
  • Raymond M Schiffelers, Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, Holland
The conventional clinical formulation of paclitaxel (PTX), Taxol®, consists of Cremophor® EL (CrEL) and ethanol. CrEL-formulated PTX is associated with acute hypersensitivity reactions, anemia and cardiovascular events. In this study, the authors investigated the effects of CrEL-PTX on red blood cells (RBCs) and compared these with the effects observed after exposure to the novel nanoparticle albumin-bound PTX, marketed as Abraxane®. Results: The authors demonstrate that CrEL is primarily responsible for RBC lysis and induction of phosphatidylserine exposure. Phosphatidylserine-exposing RBCs showed increased association with endothelial cells in culture. The authors also identified CrEL as being responsible for vesiculation of RBCs. This is the first time that excipients have been shown to be involved in microvesicle formation. Microvesicles were taken up by endothelial cells. Conclusion: These results offer new insights into the side effect profile of Taxol, which is likely to have implications for patients with erythrocyte disorders. Abraxane did not induce any of these effects on RBCs, indicating that the choice of excipients can have a pronounced influence on the efficacy and side effects of drug molecules
OriginalsprogEngelsk
TidsskriftNanomedicine
Vol/bind8
Nummer7
Sider (fra-til)1127-1135
Antal sider9
ISSN1743-5889
DOI
StatusUdgivet - jul. 2013

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