Synthetic high-density lipoproteins loaded with an antiplatelet drug for efficient inhibition of thrombosis in mice

Abstract

Antiplatelet agents offer a desirable approach to thrombosis prevention through the reduction of platelet reactivity. However, major bleeding events greatly attenuate the clinical outcomes of most antithrombotic agents. Therefore, the development of safer and more effective strategies to prevent vascular occlusion and avoid bleeding is urgently needed. A reconstituted nanoparticle, synthetic high-density lipoprotein (sHDL), which mimics the native HDL, has been established as clinically safe and is easily manufactured on a large scale. In this study, we propose that the delivery of the antiplatelet drug ML355, a selective inhibitor of 12(S)-lipoxygenase (12-LOX), by sHDL will efficiently inhibit thrombosis by targeting ML355 to the intended site of action, improving the pharmaceutical profile and harnessing the innate antithrombotic efficacy of the sHDL carrier. Our data show that ML355-sHDL exhibits more potent inhibition of thrombus formation in both small arterioles and larger arteries in mice without impairing the normal hemostasis in vivo.