The Ability of Poloxamers to Inhibit Platelet Aggregation Depends on their Physicochemical Properties

Summary

Poloxamers, block copolymers of polyethylene glycol (PEG) and polypropylene glycol (PPG), are thought to reduce cell-cell adhesion during vascular disorders. We examined how the amphiphilic nature of these polymers may contribute to their ability to inhibit ADP-induced platelet aggregation. Four Poloxamers (184, 188, 335 and 338) with varying PEG and PPG block lengths were examined. Of these, Poloxamer 184 at 2 mM markedly inhibited platelet aggregation. We observed that: i) Typically, less than 10% of the platelet surface is covered by Poloxamers, and greater than 99% of the polymer either remains in solution or binds soluble components in blood plasma. ii) Increasing the PEG side-chain length does not significantly augment the ability of Polox-amers to inhibit platelet aggregation. iii) Poloxamer 184, but not Polox-amers 188 and 335, significantly reduces the ability of stimulated platelets to bind fibrinogen and antibody PAC-1. The study demonstrates that the physical adsorption of some Poloxamers may allow them to inhibit platelet aggregation. The inhibition mechanism involves either binding of Poloxamers to platelet GPIIb-IIIa or inhibition of cellular activation pathways.

Keywords

Thrombosis - Pluronic^® - RheothRx^® - differential scanning colorimetry - flow cytometry

• References

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