Abstract
In this paper, an effective method of accelerating urokinase-administrated thrombolysis through a rotating magnetic field (RMF) of guided magnetic nanoparticles (NPs) in the presence of low-dose urokinase is proposed. The dispersed Fe3O4 NPs mixed with urokinase were injected into microfluidic channels occluded by thrombus prepared in vitro. These magnetic NPs aggregated into elongated clusters under a static magnetic field, and were then driven by the RMF. The rotation of Fe3O4 aggregates produced a vortex to enhance the diffusion of urokinase to the surface of the thrombus and accelerate its dissolution. A theoretical model based on convective diffusion was constructed to describe the thrombolysis mechanism. The thrombus lysis speed was determined according to the change of the thrombus dissolution length with time in the microfluidic channel. The experimental results showed that the thrombolysis speed with rotating magnetic NPs is significantly increased by nearly two times compared with using the same dose of pure urokinase. This means that the magnetically-controlled NPs approach provides a feasible way to achieve a high thrombolytic rate with low-dose urokinase in use.
Highlights
Thromboembolism is a common cardiovascular disease that threatens the life of human beings [1,2]
Many clinical trials have proved the value of thrombolytic agents, such as urokinase [5], streptokinase [6,7], tissue-type plasminogen activator (t-PA) [8], and so on in the treatment of venous and arterial thromboembolic diseases
The results show that the thrombolysis mainly relied on the urokinase activity, and the thrombolysis pure NPs, the thrombus lysis speed is only about three μm/min, even when the NPs concentration is speed be mg/mL
Summary
Thromboembolism is a common cardiovascular disease that threatens the life of human beings [1,2]. Many clinical trials have proved the value of thrombolytic agents, such as urokinase [5], streptokinase [6,7], tissue-type plasminogen activator (t-PA) [8], and so on in the treatment of venous and arterial thromboembolic diseases. Large therapeutic doses of the agents are always needed to lyse the clot and reestablish antegrade blood flow for a shortened thrombolysis time [9,10]. This may in turn result in the potential risks of symptomatic intracranial hemorrhages [11,12,13]. As a non-invasive technique, ultrasound is utilized to reduce the infusion time and provide a great incidence of complete lysis with a low rate of bleeding in treatment of deep-vein thrombosis (DVT) [14,15]
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