Magnetic nanoparticle drug carriers and their study by quadrupole magnetic field-flow fractionation

Abstract

Magnetic nanoparticle drug carriers continue to attract considerable interest for drug targeting in the treatment of cancers and other pathological conditions. The efficient delivery of therapeutic levels of drug to a target site while limiting nonspecific, systemic toxicity requires optimization of the drug delivery materials, the applied magnetic field, and the treatment protocol. The history and current state of magnetic drug targeting is reviewed. While initial studies involved micrometer-sized and larger carriers, and work with these microcarriers continues, it is the sub-micrometer carriers or nanocarriers that are of increasing interest. An aspect of magnetic drug targeting using nanoparticle carriers that has not been considered is then addressed. This aspect involves the variation in the magnetic properties of the nanocarriers. Quadrupole magnetic field-flow fractionation (QMgFFF) is a relatively new technique for characterizing magnetic nanoparticles. It is unique in its capability of determining the distribution in magnetic properties of a nanoparticle sample in suspension. The development and current state of this technique is also reviewed. Magnetic nanoparticle drug carriers have been found by QMgFFF analysis to be highly polydisperse in their magnetic properties, and the strength of response of the particles to magnetic field gradients is predicted to vary by orders of magnitude. It is expected that the least magnetic fraction of a formulation will contribute the most to systemic toxicity, and the depletion of this fraction will result in a more effective drug carrying material. A material that has a reduced systemic toxicity will allow higher doses of cytotoxic drugs to be delivered to the tumor with reduced side effects. Preliminary experiments involving a novel method of refining a magnetic nanoparticle drug carrier to achieve this result are described. QMgFFF is used to characterize the refined and unrefined material.

Figure 1

The quadrupole electromagnet of the field-flow fractionation system. The helical channel, held above the magnet in the photograph, is lowered into the quadrupole aperture below for particle analysis.

Figure 2

Binary fractionation of the magnetic nanoparticle sample. The first peak is eluted at the initial magnetic field gradient and corresponds to the less magnetic fraction. The second peak is obtained when the channel is removed from the aperture of the quadrupole magnet, and corresponds to the more magnetic fraction.

Figure 3

Elution curves for the supplied magnetic nanoparticle sample (peak maximum at around 60 minutes), and for the fraction retained in the channel at 82 mT (peak maximum at around 75 minutes). The dashed line shows the decay of magnetic field at the outer channel wall (see right hand axis).

Figure 4

Elution curves for the original magnetic nanoparticle sample (peak maximum at around 60 minutes), and for the fraction retained in the channel at 43 mT (peak maximum at around 80 minutes). The dashed line shows the decay of magnetic field at the outer channel wall (see right hand axis).

Figure 5

The calculated equivalent spherical core diameter distributions on a logarithmic scale for the original magnetic nanoparticle sample, and for the samples collected after retention in the channel at 82 mT amd 43 mT.

Figure 6

The calculated magnetite core mass distributions on a logarithmic scale for the original magnetic nanoparticle sample, and for the samples collected after retention in the channel at 82 mT and 43 mT.