title: Taxol(®)-induced phosphatidylserine exposure and microvesicle formation in red blood cells is mediated by its vehicle Cremophor(®) EL.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Clinical Chemistry & Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Pieter
authors: P
authors: Vader
authors: Marcel Ham
authors: MH
authors: Fens
authors: Nikoleta
authors: N
authors: Sachini
authors: Brigitte A
authors: BA
authors: van Oirschot
authors: Grietje
authors: G
authors: Andringa
authors: Antoine Cg
authors: AC
authors: Egberts
authors: Carlo Ajm
authors: CA
authors: Gaillard
authors: Jan T
authors: JT
authors: Rasmussen
authors: Richard
authors: R
authors: van Wijk
authors: Wouter W
authors: WW
authors: van Solinge
authors: Raymond M
authors: RM
authors: Schiffelers
mesh_terms: D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects*; D005434:Flow Cytometry; D005990:Glycerol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry; D006461:Hemolysis / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects; D006801:Humans; D017239:Paclitaxel / Q000009:adverse effects* / Q000737:chemistry*; D010718:Phosphatidylserines / Q000009:adverse effects* / Q000737:chemistry*
chemical_list: D010718:Phosphatidylserines; C000515:cremophor EL; D017239:Paclitaxel; D005990:Glycerol