Iron oxide core oil-in-water nanoemulsion as tracer for atherosclerosis MPI and MRI imaging

Int J Pharm. 2017 Nov 5;532(2):669-676. doi: 10.1016/j.ijpharm.2017.09.010. Epub 2017 Sep 9.

Abstract

Purpose: For early atherosclerosis imaging, magnetic oil-in-water nanoemulsion (NE) decorated with atheroma specific monoclonal antibody was designed for Magnetic Particle Imaging (MPI) and Magnetic Resonance Imaging (MRI). MPI is an emerging technique based on direct mapping of superparamagnetic nanoparticles which may advantageously complement MRI.

Methods: NE oily droplets were loaded with superparamagnetic iron oxide nanoparticles of 7, 11 and 18nm and biofunctionalized with atheroma specific scFv-Fc TEG4-2C antibody.

Results: Inclusion of nanoparticles inside NE did not change the hydrodynamic diameter of the oil droplets, close to 180nm, nor the polydispersity. The droplets were negatively charged (ζ=-30mV). In vitro MPI signal was assessed by Magnetic Particle Spectroscopy (MPS). NE displayed MRI and MPS signals confirming its potential as new contrast agent. NE MPS signal increase with NPs size close to the gold standard (Resovist). In MRI, NE displayed R2* transversal relaxivity of 45.45, 96.04 and 218.81mM-1s-1 for 7, 11 and 18nm respectively. NE selectively bind atheroma plaque both in vitro and ex vivo in animal models of atherosclerosis.

Conclusion: Magnetic NE showed reasonable MRI/MPS signals and a significant labelling of the atheroma plaque. These preliminary results support that NE platform could selectively image atherosclerosis.

Keywords: Atherosclerosis; Human antibodies; Iron oxide nanoparticles; Magnetic particle imaging; Nanoemulsion.

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / diagnostic imaging*
  • Atherosclerosis / immunology
  • Contrast Media / administration & dosage*
  • Contrast Media / chemistry
  • Diglycerides / administration & dosage
  • Diglycerides / chemistry
  • Emulsions
  • Female
  • Ferric Compounds / administration & dosage*
  • Ferric Compounds / chemistry
  • Humans
  • Magnetic Phenomena
  • Magnetic Resonance Imaging
  • Mice, Knockout
  • Nanostructures / administration & dosage
  • Nanostructures / chemistry
  • Plaque, Atherosclerotic / diagnostic imaging*
  • Plaque, Atherosclerotic / immunology
  • Rabbits
  • Single-Chain Antibodies / administration & dosage*
  • Single-Chain Antibodies / chemistry
  • Water / administration & dosage
  • Water / chemistry

Substances

  • Apolipoproteins E
  • Contrast Media
  • Diglycerides
  • Emulsions
  • Ferric Compounds
  • Single-Chain Antibodies
  • Water
  • ferric oxide
  • miglyol 840