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Complement activation by polyethoxylated pharmaceutical surfactants: Cremophor-EL, Tween-80 and Tween-20
Zsóka Weiszhár1, Judit Czúcz, Csaba Révész
1Seroscience Ltd., Nagyvárad tér 4, 1089 Budapest, Hungary.
Summary
Pharmaceutical surfactants like Cremophor-EL and Tween-80 activate the complement system, potentially causing hypersensitivity side effects. This study demonstrates their role in immune responses to nanomedicines.
Area of Science:
- Pharmaceutical Science
- Immunology
- Nanomedicine
Background:
- Pharmaceutical surfactants are crucial in drug formulation.
- Understanding their immunosafety is vital for patient well-being.
- Polyethoxylated surfactants are common in intravenous nanomedicines.
Purpose of the Study:
- To investigate the in vitro complement system activation by polyethoxylated surfactants.
- To determine if pharmaceutical formulations containing these surfactants elicit similar immune responses.
- To explore the link between surfactant-induced complement activation and drug-induced hypersensitivity.
Main Methods:
- In vitro experiments using normal human serum and plasma.
- Assays to detect complement activation products (C3a, C5a, C5b-9).
- Comparison of serum reactivity to drug-free and drug-loaded formulations (Paclitaxel, Docetaxel).
Main Results:
- Cremophor-EL and Tween-80 (Polysorbate-80) significantly activated the complement system.
- These surfactants were more potent reactogens than Tween-20.
- Drug formulations (Paclitaxel, Docetaxel) in Cremophor-EL and Tween-80 also activated complement.
- A linear correlation was observed between serum reactivity and drug formulations.
Conclusions:
- Polyethoxylated surfactants like Cremophor-EL and Tween-80 activate the complement system.
- This activation generates inflammatory mediators, contributing to hypersensitivity and immunostimulation.
- Complement activation by surfactants is a key mechanism for side effects of nanomedicines.
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