Poster Presenter

Magnetically Guided Recombinant Tissue Plasminogen Activator for Target Thrombolysis in a Rat Embolic Stroke Model.
Tony Wu, Hsiao-Pin Lin; Chia-Ning Hu; Jyh-Ping Chen; Shih-Tseng Lee; Yeu-Jhy Chang; Yunn-Hwa Ma
Taiwan

Recombinant tissue plasminogen activator (rtPA) is used for acute ischemic stroke therapy with high incidence of hemorrhagic side effect. Magnetic nanoparticles (MNP) may serve as drug carriers for target thrombolysis under the guidance of an external magnetic field; however, the strategy has never been tested with rtPA in a brain embolic model. We asked whether magnetic target delivery of rtPA allows less drug administered with similar efficacy in a rat embolic stroke model. Immobilization of rtPA to polyacrylic acid-coated MNP (95 nm) was achieved with 91% of its amidolytic activity preserved. A rat cerebral embolic model was produced by injection of a 1×1 mm whole blood clot into the right internal carotid artery (ICA). Right cerebral blood flow (CBF) was then reduced to 32 ± 7% of basal and remained stable for 3 hr, as revealed by laser Doppler flowmetry. With a 1.58 kG magnet moving back and forth along ICA, MNP-rtPA with rtPA 0.1 mg/kg restored right CBF to 66 ± 21% and 70 ± 18% of basal at 35 and 175 min after administration (n=7). Target delivery of rtPA with MNP may achieve reproducible and effective thrombolysis with <10% of a regular dose of rtPA.