Complement activation by polyethoxylated pharmaceutical surfactants

Cremophor-EL, tween-80 and tween-20

Zsóka Weiszhár, Judit Czúcz, Csaba Révész, L. Rosivall, J. Szebeni, Zoltán Rozsnyay

Research output: Contribution to journalArticle

105 Citations (Scopus)

Abstract

Immunosafety analysis of pharmaceutical surfactants is an important step in understanding the complex mechanisms by which they induce side effects in susceptible patients. This paper provides experimental evidences that polyethoxylated surfactants, Cremophor-EL and Tween-80, also known as Polysorbate-80, activate the complement system in vitro, in normal human serum and plasma. They appeared to be more efficient reactogens than their structural homolog, Tween-20. Cremophor-EL and Tween-80 promoted the generation of biologically active complement products, C3a, C5a and C5b-9. Consistently, Paclitaxel and Taxotere (Docetaxel), pharmaceuticals formulated in Cremophor-EL and Tween-80, activated the complement system in similar extent. Moreover, comparison of serum reactivity against the drug-loaded and drug-free formulations exhibited a significant linear correlation. Taken together, these results are consistent with the hypothesis that therapeutic side effects, such as acute hypersensitivity and systemic immunostimulation, caused by intravenous nanomedicines containing polyethoxylated detergents such as Cremophor-EL and Tween-80, can be attributed to complement activation-derived inflammatory mediators.

Original languageEnglish
Pages (from-to)492-498
Number of pages7
JournalEuropean Journal of Pharmaceutical Sciences
Volume45
Issue number4
DOIs
Publication statusPublished - Mar 12 2012

Fingerprint

Polysorbates
Complement Activation
Surface-Active Agents
docetaxel
Pharmaceutical Preparations
Complement C5b
Complement C3a
Nanomedicine
Complement Membrane Attack Complex
Drug Compounding
Therapeutic Uses
Paclitaxel
Serum
Detergents
cremophor EL
Immunization
Hypersensitivity

Keywords

  • Complement system
  • Drug carrier
  • Infusion hypersensitivity
  • Micelle
  • Nanoimmunosafety
  • Taxane formulation

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Complement activation by polyethoxylated pharmaceutical surfactants : Cremophor-EL, tween-80 and tween-20. / Weiszhár, Zsóka; Czúcz, Judit; Révész, Csaba; Rosivall, L.; Szebeni, J.; Rozsnyay, Zoltán.

In: European Journal of Pharmaceutical Sciences, Vol. 45, No. 4, 12.03.2012, p. 492-498.

Research output: Contribution to journalArticle

Weiszhár, Zsóka ; Czúcz, Judit ; Révész, Csaba ; Rosivall, L. ; Szebeni, J. ; Rozsnyay, Zoltán. / Complement activation by polyethoxylated pharmaceutical surfactants : Cremophor-EL, tween-80 and tween-20. In: European Journal of Pharmaceutical Sciences. 2012 ; Vol. 45, No. 4. pp. 492-498.
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