FUCOIDAN-FUNCTIONALIZED POLYSACCHARIDE PARTICLES WITH T-PA FOR TARGETED THROMBOLYTIC THERAPY

There is a dire need for innovative nanomedicine-based solutions for safe and efficient thrombolysis with a non-toxic, biocompatible, and biodegradable thrombus-targeted carrier. In the present invention, polysaccharide hydrogel submicroparticles with remarkable biocompatibility were elaborated by the inverse miniemulsion / crosslinking method. They were functionalized with a fucoidan which has a nanomolar affinity for the P-selectin overexpressed on activated platelets and endothelial cells in vascular diseases. Surprisingly, the inventors show that rtPA (i.e. Alteplase) can be loaded onto the submicroparticles by adsorption, and its amidolytic and fibrinolytic activities were maintained in vitro and in vivo. Thrombus targeting potential of these particles was validated in microfluidic assay under arterial and venous blood shear rates on recombinant P -selectin and activated platelet aggregates. The thrombolytic efficacy of the nanomedicine-based product was tested in a murine model of acute ischemic stroke, revealing faster middle cerebral artery recanalization and reduction in the brain infarct volume and blood-brain barrier permeability post-stroke, evidenced by laser speckle contrast imaging and MRI. Collectively, this proof of concept study demonstrates the potential of these particles for the precise treatment of acute thrombotic events.

Keywords: Drug delivery, Stroke, tPa
Patent Application number: European Procedure (Patents) (EPA) - 09 Juin 2020 - 20305615.5
Inventors:
CHAUVIERRE Cédric,LETOURNEUR Didier

Reference:

BIO20221-T1

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Patent filling date: 2020-06-09

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