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 micron-sized and larger carriers, and work with these microcarriers continues, it is the sub-micron 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.

Maghemite Functionalization for Antitumor Drug Vehiculization

“…For the purpose of efficiently exploiting the EPR effect for disease detection as well as cancer treatment, the molecular weight of a drug should be more than 40 kDa (Maeda et al, 2009). Cut-off sizes for pores in cases of various tumors are in the range between 380 and 780 nm (Brigger et al, 2002;Williams et al, 2009). …”

Antitumor effect of human TRAIL on adenoid cystic carcinoma using magnetic nanoparticle–mediated gene expression

“…23 Magnetic nanoparticles have been used in drug delivery and rapid biological separation. [24][25][26][27][28][29][30][31][32] Several previous studies demonstrated that DNA molecules can bind to magnetic nanoparticles by noncovalent bonds and have used this capacity to increase transfection efficiency by applying a magnetic field to the target site. [33][34][35][36][37][38] To further develop this novel treatment for ACC, we used polymer-modified iron oxide nanoparticles as vector, prepared by alkaline co-precipitation in the presence of the cationic polymer PEI.…”

Characterization of magnetic nanoparticles using programmed quadrupole magnetic field-flow fractionation

“…The quadrupole magnetic field-flow fractionation (QMgFFF) system has been described previously (Carpino et al 2005a(Carpino et al ,b, 2007Williams et al 2009a). The quadrupole electromagnet was designed and assembled in our laboratory.…”

“…Early attempts to develop MgFFF were not generally very successful for various reasons principally associated with non-ideal channel geometry and field arrangements. The literature concerning these early attempts has been described by us previously (Carpino et al 2005a,b;Williams et al 2009a). It was noted above that FFF optimally requires the field and/or field gradient to be uniform across the breadth of the channel, and that the channel also be of uniform thickness across its breadth.…”