Fabrication of pH-sensitive magnetic metal-organic framework for controlled-release of heparin

Abstract

Heparin, the most widely used anticoagulant drug in the world today, suffers from the risk of overdose and a short serum half-life, limiting its clinical applications. Concerning the controlled, sustained, and targeted release of heparin, a delivery system was fabricated in this research using the layered composites of Fe3O4 magnetic particles and pH-sensitive metal-organic framework, Fe3O4@ZIF-8. The composite demonstrated a high loading capacity for the heparin, 66.8 mg/g. The composite had a saturation magnetization of 1.5 emu/g and thus owned a magnetic targeting function, i.e. drug can be centered at a certain point using an external magnetic field. The anticoagulant activity was assessed by monitoring their activated partial thromboplastin time. The results showed that the pH-responsive and sustained release of the heparin reduced the systemic adverse effects associated with high concentrations. Moreover, control over the dose exhibited excellent anticoagulant features with fewer side effects.