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The endothelium was originally thought to be a simple passive barrier between the intravascular and extravascular compartment but is now viewed as an organ whose function is critical to maintaining hemostasis and promoting vascular health. 1 Hemostasis acts as an interplay between blood platelets, coagulation and fibrinolysis proteins, and endothelial cells. Following accidental vascular injury, the hemostatic system initiates vascular events, restores the hemostatic balance, and prevents a pathological extension of hemostasis, ie, thrombosis. Hemostasis is a tightly regulated process that ensures vascular integrity.

Keywords: drug delivery, antiplatelet, RGD, aggregation, coagulation system, biocompatibility Our results provide proof-of-principle evidence that AgNPs may be used as an effective delivery platform for antiplatelet drugs.

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AgNPs-EPI regulated levels of 6-keto-PGF1alpha, tPa, vWf and cGMP produced in thrombin stimulated HMEC-1 cells.Ĭonclusion: AgNPs-EPI show anti-aggregatory activity at concentrations lower than those required by the free drug acting via regulation of platelet aggregation, blood coagulation, and endothelial cell activity. AgNPs-EPI caused prolongation of the occlusion time in the presence of collagen/ADP and collagen/adrenaline. AgNPs-EPI inhibited aggregation-induced P-selectin expression and GPIIb/IIIa conformational changes in platelets. Preincubation of platelets with AgNPs-EPI protected by mitochondrial oxidative phosphorylation capacity. The synthesized AgNPs-EPI did not affect the viability of platelets, endothelial cells and erythrocytes. The molecules of this drug are directly bonded to the surface of the nanoparticles. Results: We describe the synthesis of AgNPs using eptifibatide as the stabilizing ligand. Finally, the effect of AgNPs-EPI on endothelial cells was measured by the levels of 6-keto-PGF1alpha, tPa, cGMP and vWF.

The influence of AgNPS-EPI on blood coagulation science was assessed.

The surface amount of platelet receptors such as P-selectin and GPIIb/IIIa was measured. The effect of AgNPs-EPI on the aggregation of washed platelets was measured by light aggregometry and the ex vivo occlusion time was determined using a reference laboratory method. Platelet mitochondrial respiration was measured using the Oxygraph-2k, a high-resolution modular respirometry system. Cytotoxicity was measured in microvascular endothelial cells (HMEC-1), platelets and red blood cells. Methods: Spherical AgNPs linked to eptifibatide were synthesized and characterized. Purpose: In the search for new drug delivery platforms for cardiovascular diseases and coating of medical devices, we synthesized eptifibatide-functionalized silver nanoparticles (AgNPs-EPI) and examined the pharmacological activity of AgNPs-EPI on platelets and endothelial cells in vitro and ex vivo. Justyna Hajtuch, 1 Eliza Iwicka, 1 Anna Szczoczarz, 1 Damian Flis, 1 Elżbieta Megiel, 2 Piotr Cieciórski, 2 Marek Witold Radomski, 3 Maria Jose Santos-Martinez, 4 Iwona Inkielewicz-Stepniak 1ġDepartment of Pharmaceutical Pathophysiology, Medical University of Gdansk, Gdansk, Poland 2Faculty of Chemistry, University of Warsaw, Warsaw, Poland 3Department of Anatomy, Physiology and Pharmacology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada 4School of Pharmacy and Pharmaceutical Sciences and School of Medicine, Trinity College Dublin, Dublin, Dublin 2, IrelandĬorrespondence: Iwona Inkielewicz-Stepniak, Tel +48, Fax +48, Email

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