A Novel Scheme for Nanoparticle Steering in Blood Vessels Using a Functionalized Magnetic Field

Abstract

Magnetic drug targeting is a drug delivery approach in which therapeutic magnetizable particles are injected, generally into blood vessels, and magnets are then used to guide and concentrate them in the diseased target organ. Although many analytical, simulation, and experimental studies on capturing schemes for drug targeting have been conducted, there are few studies on delivering the nanoparticles to the target region. Furthermore, the sticking phenomenon of particles to vessels walls near the injection point, and far from the target region, has not been addressed sufficiently. In this paper, the sticking issue and its relationship to nanoparticle steering are investigated in detail using numerical simulations. For wide ranges of blood vessel size, blood velocity, particle size, and applied magnetic field, three coefficient numbers are uniquely generalized: vessel elongation, normal exit time, and force rate. With respect these new parameters, we investigated particle distribution trends for a Y-shaped channel and computed ratios of correctly guided particles and particles remaining in the vessel. We found that the sticking of particles to vessels occurred because of low blood flow velocity near the vessel walls, which is the main reason for low targeting efficiency when using a constant magnetic gradient. To reduce the sticking ratio of nanoparticles, we propose a novel field function scheme that uses a simple time-varying function to separate the particles from the walls and guide them to the target point. The capabilities of the proposed scheme were examined by several simulations of both Y-shaped channels and realistic three-dimensional (3-D) model channels extracted from brain vessels. The results showed a significant decrease in particle adherence to walls during the delivery stage and confirmed the effectiveness of the proposed magnetic field function method for steering nanoparticles for targeted drug delivery.

Functionalized Magnetic Force Enhances Magnetic Nanoparticle Guidance: From Simulation to Crossing of the Blood–Brain Barrier <italic>In Vivo</italic>

“…To address this concern, the concept of an FF was introduced [3]. In brief, the concept involves release of MNPs from the vessel wall by reversing the magnetic direction periodically.…”

“…However, using a constant magnetic force may cause the particles to aggregate or stick to vessel walls, which can lead to blockages. To address this concern, we previously published the use of a functionalized magnetic field, or a field function (FF), to replace the constant magnetic force [3][4]. By intentionally changing the direction of the magnetic field, sticking and aggregation no longer occur.…”

Simulation studies of a novel electromagnetic actuation scheme for focusing magnetic micro/nano-carriers into a deep target region

“…The block was filled with an environment that has the characteristics of blood (the density is 1050 kg/m 3 and the viscocity is 0.004 Pa.s 25 ). Then, the proposed focusing scheme was applied to a 3-D model of a realistic vessel, as shown in Fig 3b. Steadily-creeping blood flow was considered, flowing into the channel from the inlet and exiting the channel from the outlets.…”

“…The particles were assumed to be spherical magnetite particles with a diameter (d p ) of 500 nm. 25 The blood flow inside the channels was simulated as a steady state laminar flow, and its velocity profile was calculated using the computational fluid dynamics (CFD) module in COMSOL.…”

“…24 Based on the extracted information, a 3-D model of the vessel was created using CAD software and imported to the COMSOL software to simulate particle trajectories. 25 The channel consisted of one inlet for blood flow and SPPs and six outlets. The blood flows into the channel from the inlet and exits the channel from the outlets.…”