Drug-loaded Nanoparticles Reduced Platelet Aggregation and Blood Coagulation

Kagya Amoako^1*Sarah Majin¹Afrida Malik¹Pratima Poudel¹E. Vincent S. Faustino²Nubia Zuverza²John Hwa²Seyedtaghi Takyar²Susan M. Shea³

• ¹University of New Haven, West Haven, United States
• ²Yale University, New Haven, United States
• ³University of Pittsburgh, Pittsburgh, United States

Surface-induced thrombosis is a critical clinical issue, contributing to significant morbidity and mortality. Approximately 40% of all medical device-related complications are due to thrombosis, with an estimated 100,000 deaths annually in the United States alone attributable to device-induced thrombotic events. The thrombi mature around platelets (PLT) clumps following their adhesion to the artificial surface (AS) and activation to release many potent clot promoting proteins. The surface of the activated PLT also becomes a substrate for clot potentiating protein complexes supporting the synthesis of fibrin that amasses clot. PLTs are therefore targeted to limit thrombosis. This study investigated anti-platelet lipid nanoparticles (anti-PLT LNPs) formulated with small molecule, nitric oxide (NO) cargo. Drug release activity was detected after 22 weeks of storage, exhibited mammalian cell biocompatibility, inhibited PLT aggregation (up to 84.4%, p< 0.01), and reduced blood coagulation (up to threefold increase in ACT, p< 0.05). These findings highlight the potential of anti-PLT LNP as a platform for developing customized and targeted PLT therapies. Surface-induced thrombosis remains a major challenge in blood-contacting medical devices, where platelet activation drives rapid clot formation. To address this, we aimed to develop and evaluate nitric oxide (NO)–releasing anti-platelet lipid nanoparticles (anti-PLT LNPs) as a targeted antithrombotic strategy. Anti-PLT LNPs were formulated, characterized for physicochemical properties and NO release, and assessed for platelet aggregation, mammalian cell biocompatibility, and effects on whole-blood coagulation. The LNPs maintained measurable NO release after 22 weeks of storage, showed high cell biocompatibility, inhibited platelet aggregation by up to 84.4% (p < 0.01), and prolonged clotting time with up to a threefold increase in ACT (p < 0.05). These results demonstrate the potential of NO-releasing LNPs as a customizable platform for targeted, platelet-focused thrombosis mitigation.