Pluronic block copolymers inhibit platelet aggregation role of critical micelle concentration & side chain length

Non-ionic block copolymer surfactants such as Pluronics(R) (PEO-PPO-PEO) have been shown to inhibit platelet aggregation and thrombosis. The mechanisms regulating this inhibition are yet unknown. In this study, we examined how the physico-chemical properties of pluronics may contribute to their inhibitory role. Platelet rich plasma from human volunteers was stimulated with adenosine 5'-diphosphate (ADP) and sheared at a constant rate of 200/s using cone-plate viscometry. Cell aggregation kinetics were monitored using flow cytometry. The inhibition efficacy of four Pluronics (F-68, P-105, L-64 and F-108) which have varying polymer segment lengths and critical micelle concentrations (CMC) was examined. 2mM F-68, which has a high CMC of 8.33 mM was found to inhibit platelet aggregation by /spl sim/50%, while P-105 with a low CMC of 0.11 mM did not have a statistically significant inhibitory role. Overall, molecules with longer PEO side chains like F-68 and F-108 were better inhibitors than L-64 and P-105 respectively. Together, these results suggest a model where the aggregation inhibitory efficacy of Pluronics is dependent on their relative binding rates either to the platelet surface, or their tendency to self-assemble into micelles. Current studies that test this model by examining the nature of platelet-polymer interactions using fluorescein labeled Pluronics are also presented.