Heparin-Peptide Nanogranules for Thrombosis-Actuated Anticoagulation

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Pharmacology

Background:

• Heparin, a widely used anticoagulant, suffers from rapid clearance and bleeding risks.
• Controlled delivery systems are needed to improve heparin's therapeutic index.
• Subcutaneous depots offer a promising strategy for sustained heparin release.

Purpose of the Study:

• To develop and characterize heparin-peptide nanogranules for controlled subcutaneous delivery.
• To investigate the on-demand activation of heparin's anticoagulant effects within the thrombus microenvironment.
• To evaluate the in vivo pharmacokinetics and pharmacodynamics of the nanogranule depot.

Main Methods:

• Fabrication of heparin-peptide nanogranules utilizing self-assembling peptide nanofibrils.
• Biophysical characterization of heparin sequestration and mechanical release mechanisms.
• In vivo studies in animal models to assess serum heparin concentrations and anticoagulant activity.

Main Results:

• Heparin-peptide nanogranules demonstrated sustained release of heparin for an order of magnitude longer than standard regimens.
• The nanogranules enabled on-demand activation of anticoagulant effects specifically at the thrombus site.
• In vivo studies confirmed prolonged and controlled anticoagulant activity with reduced bleeding risk.

Conclusions:

• Subcutaneously deliverable heparin-peptide nanogranules provide a safe and effective platform for long-lasting anticoagulation.
• This biohybrid delivery system represents a scalable approach for advanced antithrombotic nanotechnologies.
• The on-demand activation mechanism enhances therapeutic control and minimizes systemic side effects.