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

机译:Pluronic嵌段共聚物抑制血小板聚集:临界胶束浓度和侧链长度的作用

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Non-ionic block copolymer surfactants such as Pluronics (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-chemicalproperties 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 kineticswas 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 8.33mM wasfound to inhibit platelet aggregation by ~50%, while P-105 with a low CMC of 0.11mM 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-105respectively. 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 studiesthat test this model by examining the nature of platelet-polymer interactions using fluorescein labeled Pluronics are also be presented.
机译:已显示非离子嵌段共聚物表面活性剂如Pluronics(PEO-PPO-PEO)以抑制血小板聚集和血栓形成。调节该抑制的机制尚未赘言。在这项研究中,我们研究了Purlonics的物理化学性能如何有助于其抑制作用。用腺苷5'-二磷酸(ADP)刺激人类志愿者的血小板富血浆,并以锥形板粘度法以200 /秒的恒定速率剪切。使用流式细胞术监测细胞聚集动力学。检查具有不同聚合物段长度和临界胶束浓度(CMC)的四分之一(F-68,P-105,L-64和F-108)的抑制效果。 2mm f-68,其具有8.33mm的高CMC,以抑制血小板聚集〜50%,而低CMC为0.11mm的P-105没有统计学上显着的抑制作用。总体而言,具有较长的PEO侧链的分子,如F-68和F-108,比L-64和P-105更好地是更好的抑制剂。这些结果表明,Purronics的聚集抑制疗效依赖于血小板表面的相对结合速率,或其对胶束自组装成胶束的倾向的模型。还通过检查使用荧光素标记的Plulonics检查血小板聚合物相互作用的性质来测试该模型。

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