Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, tween-80 and tween-20

Zsóka Weiszhár, Judit Czúcz, Csaba Révész, László Rosivall, János Szebeni, Zoltán Rozsnyay

Research output: Article

121 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 - márc. 12 2012

ASJC Scopus subject areas

  • Pharmaceutical Science

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