Drug-loaded nanoparticles reduced platelet aggregation and blood coagulation

Surface-induced thrombosis remains a significant limitation of blood-contacting medical devices, driven primarily by platelet activation and rapid clot formation. Nitric oxide (NO), a potent endogenous antiplatelet agent, has therefore inspired the development of targeted NO-delivery strategies to mitigate device-associated thrombosis. In this study, nitric oxide-releasing antiplatelet lipid nanoparticles (anti-PLT LNPs) were formulated and characterized for their physicochemical properties and NO-release kinetics. Their platelet aggregation inhibition was evaluated in vitro, while mammalian cell biocompatibility and effects on whole-blood coagulation were evaluated using activated clotting time (ACT) measurements. Anti-PLT LNPs exhibited sustained and measurable NO release after 22 weeks of storage and demonstrated high mammalian cell biocompatibility. The nanoparticles inhibited platelet aggregation by up to 84.4% (<i>p</i> < 0.01) and significantly prolonged whole-blood clotting time, resulting in up to a threefold increase in ACT (<i>p</i> < 0.05). These findings indicate that NO-releasing anti-PLT LNPs effectively suppress platelet activation and coagulation while maintaining biocompatibility, offering a customizable and targeted approach to mitigate surface-induced thrombosis in blood-contacting medical devices.