Thrombolytic and Antiplatelet Drugs Loaded Magnetic Nanoparticles for Targeted Thrombolysis (II)

Thromboembolic stroke is a leading cause of death and disability that lacks efficient curative treatment. Thrombolytic therapy for acute ischemic stroke may salvage the ischemic penumbra, limit infarct size, and improve functional recovery and survival. However, risk of cerebral hemorrhage increases about 2 to 3 folds. With the advance of nanotechnology, we plan to resolve this problem by using magnetic nanoparticles (MNP) as carriers for antithrombotic drugs. The applied external magnetic field will capture the MNP-drug in circulation, guide, and concentrate the drug to the thromboembolic site. The dosage of thrombolytic drug is reduced, and the related side effect was decreased. Previous study has demonstrated effective magnetically targeted thrombolysis with ＜20% of a regular recombinant tissue plasminogen activator (rtPA) dosage in rat iliac embolic model. On going NSC granted project (Thrombolytic and antiplatelet drugs loaded magnetic nanoparticles for targeted thrombolysis, first year) further demonstrated the feasibility and efficacy of targeted thrombolysis with recombinant tissue plasminogen activator (rtPA) bound to MNP and retained to the target site by an external magnet in rat embolic stroke model. Current proposal , the 2nd year plan of the on going NSC project, will continue to test efficacy of magnetically targeted thrombolytic therapy in rat embolic stroke model. Two antithrombotic drugs (rtPA and aspirin) will be bound to MNP, and magnetically guide this MNP-2drugs to the clot lodging site. The thrombolytic efficacy will be evaluated by transcranial laser Doppler flowmetry, serial MRI study, and histological examination. This proposal will collaborate with researchers from colleges of engineering and medicine, and physicians. Results from this study may provide solid evidence of a blend new and effective treatment strategy for thromboembolic stroke. Further clarification of the safety and regulation issues will enable this MNP-2drugs to be a candidate agent for phase I clinical trial. Experiments are designed: Aim 1- To develop and prepare dual drugs (rtPA and aspirin) loaded MNP and determine its thrombolytic and antiplatelet efficacy in vitro. Aim 2- To determine the thrombolytic efficacy of magnetically targeted MNP-2drugs therapy in a rat embolic stroke model.

Project ID:PC10008-0670
External Project ID:NSC100-2314-B182A-093