An Intravascular Magnetic Catheter Enables the Retrieval of Nanoagents from the Bloodstream

Abstract

The clinical adoption of nanoscale agents for targeted therapy is still hampered by the quest for a balance between therapy efficacy and side effects on healthy tissues, due to nanoparticle biodistribution and undesired drug accumulation issues. Here, an intravascular catheter able to efficiently retrieve from the bloodstream magnetic nanocarriers not contributing to therapy, thus minimizing their uncontrollable dispersion and consequently attenuating possible side effects, is proposed. The device consists of a miniature module, based on 27 permanent magnets arranged in two coaxial series, integrated into a clinically used 12 French catheter. This device can capture ≈94% and 78% of the unused agents when using as carriers 500 and 250 nm nominal diameter superparamagnetic iron oxide nanoparticles, respectively. This approach paves the way to the exploitation of new "high-risk/high-gain" drug formulations and supports the development of novel therapeutic strategies based on magnetic hyperthermia or magnetic microrobots.

Keywords: intravascular devices; magnetic nanoparticles; magnetic retrieval; targeted therapy.

Figure 1

Intravascular retrieval catheter concept, structure and prototype. a) Depiction of a liver with a tumor mass and of the double access through the injection and retrieval catheters. b) Intravascular device schematization with constitutive blocks. c) Proposed catheter in the target vessel with the tip balloon in the inflated configuration and particle flow canalization (zoomed view of panel a). d) Extended view of the magnetic module. e) Magnetic particle trajectories (yellow dotted line) within the magnetic module. f) Magnetic module prototype. g) Retrieval catheter prototype.

Figure 2

Multiphysics simulation results. a) Magnetic module 2D representation in COMSOL Multiphysics environment; b) zoomed view of a portion of the magnetic module in which the internal and the external series of permanent magnets are reported; c–e) Fluidic velocity, magnetic field, and particle trajectories in the proposed magnetic module; f) FEM simulations results in terms of capture efficiency when considering a single magnet, placed either centrally or externally, and 500 nm nominal diameter nanoparticles; magnetic capture efficiency when varying magnet number g), grouping h) or caught nanoparticle diameter i). The selected configuration is the number 3 in h).

Figure 3

In vitro validation setup and results. a) In vitro validation fluidic circuit schematization. b) Comparison among theoretical (calculated through FEM) and experimental capture efficiency when considering 439 (nominal 500) and 305 (nominal 250) nm magnetic nanoparticles: experiments versus numerical simulations. Retrieval efficiency when performing multiple consecutive tests on the same prototype. Reported results refer to 500 nm c) and 250 nm d) nominal diameter magnetic nanoparticles.