A Novel Magnetic Actuation Scheme to Disaggregate Nanoparticles and Enhance Passage across the Blood–Brain Barrier

Abstract

The blood–brain barrier (BBB) hinders drug delivery to the brain. Despite various efforts to develop preprogramed actuation schemes for magnetic drug delivery, the unmodeled aggregation phenomenon limits drug delivery performance. This paper proposes a novel scheme with an aggregation model for a feed-forward magnetic actuation design. A simulation platform for aggregated particle delivery is developed and an actuation scheme is proposed to deliver aggregated magnetic nanoparticles (MNPs) using a discontinuous asymmetrical magnetic actuation. The experimental results with a Y-shaped channel indicated the success of the proposed scheme in steering and disaggregation. The delivery performance of the developed scheme was examined using a realistic, three-dimensional (3D) vessel simulation. Furthermore, the proposed scheme enhanced the transport and uptake of MNPs across the BBB in mice. The scheme presented here facilitates the passage of particles across the BBB to the brain using an electromagnetic actuation scheme.

A Novel Shared Guidance Scheme for Intelligent Haptic Interaction Based Swarm Control of Magnetic Nanoparticles in Blood Vessels

“…8). Outlet 1 was selected as the target in this simulation based on the previously reported works on particle navigation [19,22]. However, further study may be required if a different target outlet is selected.…”

“…At low fluid velocities, it is difficult to verify the effectiveness of the interaction mode because it is easier for the user to steer the MNPs. So, the fluid velocity in these experiments was set at 10 mm/s based on the blood velocity inside a real brain [9,19]. 270 particles with the initial radius of 400nm, distributed uniformly at the inlet of the realistic 3D vessel model, were released into the channel (see Figure 8).…”

“…Thus, due to these complexities, there are only a few studies related to navigation, control and automated monitoring of the collective behavior of nanoparticle swarms [17,18]. These studies mostly employ an open-loop motion control strategy for the steering of the nanoparticles [19]. In the published works, magnetic fields were either preset or manually controlled to guide the swarms to the desired position in two-dimensional (2-D) and threedimensional (3-D) vessel models [20][21][22].…”

Improving guidewire-mediated steerability of a magnetically actuated flexible microrobot

“…*Correspondence: mems@dgist.ac.kr † Sungwoong Jeon and Ali Kafash Hoshiar contributed equally to this work 1 Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, South Korea Full list of author information is available at the end of the article permanent magnets, which limits the real-time steering for a catheter.…”

“…Biomedical microrobots (here termed simply "robots") will potentially revolutionize medicine. Many research groups have studied the biomedical applications of robots, including targeted drug delivery, biopsy-taking, hyperthermia control, radioactive therapy, scaffolding applications, in vivo ablation, stenting, sensing, and marking [1][2][3][4][5][6][7]. Most robots are controlled and operated in low Reynolds number fluids [8][9][10].…”