A novel human artery model to assess the magnetic accumulation of SPIONs under flow conditions

Abstract

Magnetic targeting utilises the properties of superparamagnetic iron oxide nanoparticles (SPIONs) to accumulate particles in specified vasculature regions under an external magnetic field. As the behaviour of circulating particles varies depending on nanoparticle characteristics, magnetic field strength and flow dynamics, we established an improved ex vivo model in order to estimate the magnetic capture of SPIONs in physiological-like settings. We describe here a new, easy to handle ex vivo model of human umbilical artery. Using this model, the magnetic targeting of different types of SPIONs under various external magnetic field gradients and flow conditions was investigated by atomic emission spectroscopy and histology. Among tested particles, SPION-1 with lauric acid shell had the largest capacity to accumulate at the specific artery segment. SPION-2 (lauric acid/albumin-coated) were also successfully targeted, although the observed peak in the iron content under the tip of the magnet was smaller than for SPION-1. In contrast, we did not achieve magnetic accumulation of dextran-coated SPION-3. Taken together, the umbilical artery model constitutes a time- and cost-efficient, 3R-compliant tool to assess magnetic targeting of SPIONs under flow. Our results further imply the possibility of an efficient in vivo targeting of certain types of SPIONs to superficial arteries.

Drug delivery to atherosclerotic plaques using superparamagnetic iron oxide nanoparticles

“…These particles have a good biocompatibility profile, as well as good colloidal and blood stability, 31 and were successfully targeted to the specific artery region ex vivo under external magnetic field gradient. 17 To our knowledge, this is the first study to demonstrate the possibility of magnetic targeting of SPIONs at the wall of a large artery in a living rabbit. The histological analyses showed the accumulation of iron at the targeted regions, which confirmed our previous ex vivo data, and indicated that magnetic accumulation of this type of SPIONs is possible, at least in superficial and/or easily accessible arteries in vivo.…”

“…Our previous studies in an ex vivo artery models suggested that magnetic accumulation of certain types of SPIONs is possible even under arterial flow conditions. 17,18 Other preclinical studies indicated that SPION-loaded cells can be magnetically targeted to stented carotid arteries in vivo in order to prevent thrombosis and restenosis in a rat model. 19 By increasing the effective local doses of pharmaceutical agents, MDT may therefore represent a useful tool to improve the plaque stability and reduce inflammatory responses.…”

“…The SPION formulation used in this study as drug carrier was carefully selected based on the previous in vitro, ex vivo, and in vivo studies, which indicated its good biocompatibility, as well as good magnetic targeting properties. 17 In order to address the efficacy of targeted inhibition of proinflammatory processes in vascular injury and advanced atherosclerosis, SPION-DEXA were administered and magnetically targeted to the abdominal aorta in the rabbit model of balloon injury and diet-induced atherosclerosis.…”

Computational investigation of magnetic hydrogels and elastomers

“…Furthermore, it enables to manipulate the magnetic objects toward the specific organ or tissues of the body [112][113][114], resulting in increased drug concentration at the target tissue with low systematic toxicity. In general, the magnetic drug carrier is developed by adding highly permeable magnetic nanoparticles into a non-magnetic matrix [115][116][117], where usually the hydrophilic polymer is adopted [115,[117][118][119], due to its capability to 22 enhance the water solubility of hydrophobic drugs, extend the circulation of drugs in blood, and suppress or eliminate fast renal excretion.…”

“…where the solid and dash lines denote the distributions of the magnetic fields in the absence and presence of the magnetic hydrogel respectively. 112…”