期刊
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
卷 45, 期 4, 页码 492-498出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejps.2011.09.016
关键词
Nanoimmunosafety; Infusion hypersensitivity; Complement system; Micelle; Drug carrier; Taxane formulation
资金
- National Office of Research and Technology of Hungary [NKTH Jedlik-CARPA777]
- Government Office of the Capital City Budapest [AFSZ 48497-1/2011]
- [TAMOP-4.2.1/B-09/1/KMR]
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. (C) 2011 Elsevier B.V. All rights reserved.
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