Fucoidan-functionalized polysaccharide submicroparticles loaded with alteplase for efficient targeted thrombolytic...

Area of Science:

• Biomaterials Science
• Nanomedicine
• Vascular Biology

Background:

• Current fibrinolytic drugs for thrombotic diseases have short half-lives and risk hemorrhagic complications.
• There is a need for advanced nanomedicine solutions for targeted and safer thrombolysis.

Purpose of the Study:

• To develop biocompatible, biodegradable, and thrombus-targeted nanocarriers for enhanced fibrinolysis.
• To evaluate the efficacy of fucoidan-functionalized nanoparticles loaded with alteplase for treating acute ischemic stroke.

Main Methods:

• Fabrication of fucoidan-functionalized hydrogel polysaccharide submicroparticles via inverse miniemulsion/crosslinking.
• Loading particles with alteplase for targeted delivery.
• Validation of thrombus targeting using microfluidic assays and in vivo murine models of ischemic stroke.

Main Results:

• Successfully developed biocompatible fucoidan-functionalized hydrogel submicroparticles.
• Demonstrated site-specific fibrinolysis through fucoidan's interaction with P-selectin on activated platelets and endothelial cells.
• In vivo studies showed faster middle cerebral artery recanalization, reduced infarct lesions, and decreased blood-brain barrier permeability compared to free alteplase.

Conclusions:

• Fucoidan-functionalized nanoparticles represent a promising biomaterial-based nanomedicine for precise treatment of acute thrombotic events.
• This targeted approach offers improved therapeutic efficacy and safety for conditions like ischemic stroke.
• The study validates the potential of P-selectin-targeted nanocarriers for thrombus treatment.