Core-shell magnetic nanoparticles of heparin conjugate as recycling anticoagulants

Abstract

Polyvinyl alcohol-shell magnetic nanoparticles (PVA-shell MNPs, PMNPs) were successfully prepared by in-situ co-precipitation process. Heparin (HEP) was then covalently conjugated on the PMNPs by using aminotrimethoxysilane (ATMS) and 4,4-diphenyl methane diisocyanate (HMDI) as molecular coupling agent (spacer). The morphology of the core-shell PMNPs was examined using transmission electron microscope (TEM), X-ray diffraction (XRD), and Raman spectrometry to demonstrate the core-shell structure, as well as X-ray photoelectron spectroscope (X-PS) to provide direct evidence that the heparin molecules were immobilized on the surface of the core-shell PMNPs. Anticoagulant activity was evaluated with several parameters including activated partial thrombin time (APTT), prothrombin time (PT), fibrinogen time (FT), and thrombin time (TT). The results show that longer spacer would give better anticoagulant activity since lower steric hindrance can induce higher heparin grafting density. It might be anticipated that PMNPs of heparin conjugate can be used as anticoagulants instead of traditional free heparin, owing to its recycling characteristics by magnetic fields.