The ability of poloxamers to inhibit platelet aggregation depends on their physicochemical properties

• Published in: Thrombosis and haemostasis Vol. 86; no. 6; p. 1532
• Main Authors: Ahmed, F, Alexandridis, P, Shankaran, H, Neelamegham, S
• Format: Journal Article
• Language: English
• Published: Germany 01.12.2001
• Subjects: Adenosine Diphosphate - antagonists & inhibitors; Adenosine Diphosphate - pharmacology; Adsorption; Antibodies, Monoclonal - metabolism; Calorimetry, Differential Scanning; Drug Evaluation, Preclinical; Fibrinogen - metabolism; Humans; Kinetics; Micelles; Microspheres; Molecular Weight; Platelet Aggregation - drug effects; Platelet Aggregation Inhibitors - chemistry; Platelet Aggregation Inhibitors - pharmacology; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Poloxamer - chemistry; Poloxamer - pharmacology; Protein Binding; Solubility; Structure-Activity Relationship; Surface Properties; Viscosity
• ISSN: 0340-6245
• DOI: 10.1055/s-0037-1616759

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.