The effect of single and multiple intravenous administration of magnetic iron oxide nanoparticles to rats on the blood coagulation

Abstract

Background . Magnetic nanoparticles (MNPs) are considered as a means of targeted delivery, diagnosis and treatment, the main route of administration for them is intravascular, so it is important to evaluate their interaction with blood. We previously studied the effect of two samples of MNPs (MNP1 and MNP2) on the viability of human umbilical vein endothelial cells and hemocompatibility on human heparinized whole blood. Objective . The aim of the present study is to evaluate the effect of MNP1 and MNP2 on hemostasis. Design and methods . MNP1 and MNP2 suspensions were administered intravenously in outbred Wistar rats once and repeatedly (7 days); prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and fibrinogen concentration were evaluated before administration, on the 15th and 31st days after the last administration. Results . It was shown that MNP1 and MNP2 decreased in TT and an increased in APTT (in the MNCH1 and MNCH2 groups) as well as its increased in the fibrinogen concentration (in the MNCH2 groups) after a single dose (400 mg/kg) on day 31. Repeated administration of 60 mg/kg MNCH1 led to decrease the fibrinogen concentration (day 15) and to increase in APTT (day 31) in females. Repeated administration of 10 mg/kg MNCH2 caused an increase in APTT (males and females) and a decrease in fibrinogen concentration (females) on the 15th and 31st days. Conclusion . Thus, a single administration of 400 mg/kg MNPs caused an imbalance in the blood coagulation system, changes were independed on the sex of animals, but depended on the time after administration. Repeated administration of MNPs caused gender-dependent hypocoagulation changes (more pronounced in females).