# Drug-loaded nanoparticles reduced platelet aggregation and blood coagulation

## TL;DR

This study shows that drug-loaded nanoparticles can significantly reduce platelet aggregation and blood clotting, offering a promising solution for blood-contacting medical devices.

## Contribution

The development of nitric oxide-releasing lipid nanoparticles that effectively and safely inhibit platelet activation and coagulation.

## Key findings

- Anti-PLT LNPs inhibited platelet aggregation by up to 84.4% (p < 0.01).
- The nanoparticles prolonged whole-blood clotting time, increasing ACT by up to threefold (p < 0.05).
- Anti-PLT LNPs showed sustained NO release for 22 weeks and high mammalian cell biocompatibility.

## Abstract

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% (p < 0.01) and significantly prolonged whole-blood clotting time, resulting in up to a threefold increase in ACT (p < 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.

Modification of platelet function using nanomedicine. BioRendered.Illustration showing platelet surface interactions. On the left, the prothrombinase complex on an activated platelet surface converts Factor II (FII) to thrombin. On the right, after drug delivery, the surface remains resting, blocking thrombin production. Key labels include \"Activated platelet surface,\" \"Resting surface after drug delivery,\" \"Platelet surface interactions,\" and \"Platelet intracellular interactions.\" Calcium ions (Ca²⁺) and other elements like Factor Va (FVa) and Factor Xa (FXa) are depicted.

Modification of platelet function using nanomedicine. BioRendered.