Effect of differently coated silver nanoparticles on hemostasis

Abstract

With the emergence of nano-enabled medical devices (MDs) for the use in human medicine, ensuring their safety becomes of crucial importance. Hemocompatibility is one of the major criteria for approval of all MDs in contact with blood (e.g. vascular grafts, stents, or valves). Silver nanoparticles (AgNPs) are among the most used nanomaterials for MDs due to their biocidal activity; however, detailed knowledge on their hemostatic effects is still lacking.

This study aimed to evaluate comprehensively AgNPs effects on hemostasis in human blood by exploiting combination of affordable and clinically relevant techniques.

Differently stabilized AgNPs were prepared using sodium bis(2-ethylhexyl)sulphosuccinate (AOT), polyvinylpyrrolidone (PVP), poly-L-lysine (PLL), and bovine serum albumin (BSA) as coating agents. They were tested for hemolytic activity, induction of platelet aggregation, plasmatic coagulation, thrombin generation, and hemostasis in whole blood.

All AgNPs were found to cause dose-dependent hemolysis. The BSA-, AOT-, and PVP-coated AgNPs delayed plasmatic coagulation, while only PLL-AgNPs inhibited plasmatic coagulation, induced platelet activation, and interfered with hemostasis by delaying clotting time and decreasing clot firmness in whole blood.

Obtained results demonstrate that a combination of different techniques should be used for reliable assessment of AgNPs hemostatic effects highlighting the need for a standardized approach in sampling and experimental protocols.

Keywords:

• Blood coagulation
• hemolysis
• nano-enabled medical devices
• platelet aggregation

Authors Contributions

Concept and design: Marija Milić, Barbara Vuković, Vatroslav Šerić, and Ivana Vinković Vrček; Analysis and provision of data: Marija Milić, Barbara Vuković, Rinea Barbir, Barbara Pem, Mirta Milić; Interpretation of data: Marija Milić, Barbara Vuković, Eleonore Frőhlich, and Ivana Vinković Vrček; Critical writing: Marija Milić, Rinea Barbir, Barbara Pem, and Ivana Vinković Vrček; Revising the intellectual content: Marija Milić, Vatroslav Šerić, Eleonore Frőhlich, and Ivana Vinković Vrček

Conflicts of Interest

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Supplementary Material

Supplemental data for this article can be accessed on the publisher’s website.

Additional information

Funding

This study was financially supported by the Croatian Science Foundation (grant HRZZ-IP-2016-06-2436). This study is based upon collaborative work from COST Action CA 17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST (European Cooperation in Science and Technology)