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One of the main challenges faced in treating disease is the damage caused to non-diseased, healthy tissue as a result of drug toxicity.
One solution is the direct delivery of therapeutic agents to specific targets via magnetic drug targeting (MDT). In MDT, magnetic particles coated with therapeutic agents are injected into the circulation and then directed to disease targets by means of an externally applied magnetic field.
One limitation of MDT is that the magnetic gradient decreases with increasing distance to the target, but the necessary magnetic gradient needs to be maintained in order to control the concentration of nanoparticles at desired locations. Another limitation is the small size that magnetic nanoparticles need to be in order for them to be superparamagnetic.
Superparamagnetism enables the particles to move freely in the circulation until they are in the presence of the magnetic field, at which point they become trapped at the desired location. Once this field is removed, the nanoparticles lose their magnetization, which prevents embolization in blood vessels.
Figure 1. Drug-loaded carrier is typically composed of a magnetic core and a biocompatible coating material. The magnetic core was made from different materials such as Fe3O4, Fe2O3, or Fe. The coating materials are Au, PEG, or SiO2. Based on the biokinetics of particles, a drug carrier ranging from 10–200 nm in diameter is optimal for in vivo delivery, as the small particles (D<10 nm) escape by renal clearance and the large ones (D>200 nm) are sequestered by the reticuloendothelial system of the spleen and liver.
However, the small size needed to achieve superparamagnetism also reduces the strength of the particles’ magnetic response. This makes magnetic direction of the particles difficult, given the drag force of the blood flow. Another limitation regarding size, is that small particles (less than 10nm) are quickly eliminated through renal clearance, while large ones (more than 200 nm) are cleared by the reticuloendothelial system.
Another important factor is the lifetime of MNPs, which is typically preserved by coating the magnetic core of the drug in a protective, non-magnetic material such as gold, silica or polyethylene glycol.
In order to assess drug carrier capture during MDT, Thodsaphon Lunnoo and Theerapong Puangmali (Khon Kaen University, Thailand) produced a computational model of the capture of nanoparticles Fe3O4, Fe2O3 and Fe in mimicked arterial flow and in the presence of an externally implanted superconductive magnet.
The authors referred to the model as a “simple, fast, and relatively accurate guideline for designing and optimizing the capture efficiency in MDT.”
Given that a carrier size range of around 10 to 200nm is optimal, the authors were particularly interested in particles of this size. This carrier size range also demonstrates superparamagnetic behavior.
As reported in Nanoscale Research Letters, the capture efficiency and ability to direct the particles using the magnetic field decreased as the particle size decreased. The capture efficiency of superparamagnetic particles in the arterial flow was lower than 5%, because the magnetic response was not strong enough to withstand arterial pressures.
Furthermore, coating the nanoparticles in gold, silica or polyethylene glycol had no effect on the capture efficiency.
The study also clearly showed that nanoparticles were more concentrated at the vessel wall close to the magnetic field source, with none of the particles present in other areas, thereby confirming enhanced deposition as a result of the magnetic field being applied.
The solution the researchers suggest is to use nanoparticles in the 10-200nm size range in vessels with lower blood velocities such as microcapillaries. They also suggest the use of implanted magnets, which can be put in position using minimally invasive surgery and located close to the disease target.
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This information has been sourced, reviewed and adapted from materials provided by SpingerOpen.