The ability of poloxamers to inhibit platelet aggregation depends on their physicochemical properties.
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.
Ahmed
F
F
Department of Chemical Engineering, State University of New York at Buffalo, 14260, USA.
Alexandridis
P
P
Shankaran
H
H
Neelamegham
S
S
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002152:Calorimetry, Differential Scanning; D004353:Drug Evaluation, Preclinical; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008823:Micelles; D008863:Microspheres; D008970:Molecular Weight; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D020442:Poloxamer / Q000737:chemistry / Q000494:pharmacology*; D011485:Protein Binding; D012995:Solubility; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014783:Viscosity
D000911:Antibodies, Monoclonal; D008823:Micelles; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D020442:Poloxamer; D000244:Adenosine Diphosphate; D005340:Fibrinogen