Microemulsion-Inspired Polysaccharide Nanoparticles for an Advanced Targeted Thrombolytic Treatment.

Area of Science:

• Biomaterials Science
• Nanomedicine
• Cardiovascular Research

Background:

• Thrombotic diseases, including ischemic heart disease and stroke, are leading causes of death worldwide.
• Current thrombolytic treatments like recombinant tissue plasminogen activators (rtPA) have limitations, including a narrow therapeutic window and severe side effects.
• Existing nanoparticles often struggle with stability, biocompatibility, and robust synthesis, hindering their clinical application.

Purpose of the Study:

• To develop robust, biocompatible polysaccharide hydrogel nanoparticles for targeted thrombolytic drug delivery.
• To functionalize nanoparticles with fucoidan for enhanced binding to thrombi biomarkers (P-selectin).
• To evaluate the efficacy of nanoparticles loaded with rtPA or DNase I for thrombolysis, including synergistic effects.

Main Methods:

• Utilized an improved microemulsion-based approach to synthesize polysaccharide hydrogel nanoparticles with a mean size of 315 nm.
• Decorated nanoparticles with fucoidan to target P-selectin on thrombi.
• Loaded nanoparticles with either rtPA (for fibrin degradation) or DNase I (for neutrophil extracellular trap degradation).
• Assessed nanoparticle stability, biocompatibility, targeting capacity, and thrombolytic efficacy in vitro and in vivo.

Main Results:

• Successfully synthesized stable, biocompatible nanoparticles with optimal size and targeting capabilities.
• Demonstrated synergistic thrombolytic effects on NET-containing thrombi when loaded with both rtPA and DNase I.
• Achieved significant in vivo thrombolysis with rtPA-loaded nanoparticles at reduced doses (50% and 10% of standard) without causing secondary embolization.

Conclusions:

• Developed safe, robust, and easily synthesized polysaccharide nanoparticles as effective drug delivery agents.
• These nanoparticles show significant potential for improving thrombolytic therapy in cardiovascular diseases.
• The fucoidan-decorated nanoparticles offer a promising strategy for targeted delivery of thrombolytics, overcoming limitations of current treatments.