The use of superparamagnetic iron oxide nanoparticles (SPION) for the delivery of therapeutic molecules holds potential clinical applications, for it could provide substantial improvement over current techniques for drug delivery and gene transfection. Nanoparticles carrying therapeutic payloads could be targeted to a specific site, through directional acceleration by an external magnetic field. This field would pull the SPION to the target organ or tissue, where the biodegradable vehicles would subsequently break down, releasing drugs, DNA plasmids or bioactive molecules into surrounding tissues. An advantage that targeted delivery would have over systemic delivery is marked reduction in adverse side effects, which often decreases patient compliance. Another result of targeted delivery is that smaller dose (and cost) is required to achieve the same, or even improved, result. Others found in a rat model that with magnetic nanoparticles indomethacin had 60-fold higher concentrations and considerably reduced drug concentration in non-target organs [1
]. Furthermore, magnetically susceptible nanoparticles, controlled by an external magnetic field, have the ability to reach target tissues that are difficult to access, such as the inner ear. Though these benefits are attractive, little progress has been made towards the goal of using SPION as in-vivo
carriers of therapeutic payloads.
SPION are currently being used for cell separation [2
], flow cytometry, immunoassays [3
], and cellular labeling. One current in-vivo application of cellular labeling was made by derivatizing the nanoparticle with an HIV-TAT (Trans-Activating Transduction) peptide for promoting cellular internalization [4
]. The HIV-TAT study not only demonstrated absence of cytotoxic effects or interference with cell function, but also took advantage of the property of SPION as contrast enhancing agents for magnetic resonance imaging (MRI). This may prove valuable in both clinical applications and future ferrite nanoparticle research as a method of imaging quantification. In addition, the utilization of the TAT cell penetrating peptides may be important for targeted delivery and gene transfection of cells that are non-dividing.
A recent study has shown for the first time, in a mammal, that adenoviral transfection with the MATH-1 gene can be used to regenerate inner ear hair cells and restore hearing [5
]. MATH-1 expression within supporting cells along the Organ of Corti in the deafened cochlea, transformed these non-sensory cells into functional hair cells, and improved hearing thresholds. Nevertheless, safety limitations of adenoviruses used for gene therapy will likely deter use of this vector in clinical applications. Hence, a non-viral vector is currently being sought and preliminary studies are underway to incorporate MATH-1 plasmid DNA into a biocompatible polymeric-SPION for magnetic targeted delivery to the cochlea [6
]. This technique would overcome the immune response complications and mutation risks that are involved in viral transfection [7
]. Biodegradable poly-lactide co-glycolic acid (PLGA) polymers are attractive as carriers, because of their hydrophilicity, biocompatibility, promotion of cell membrane endocytosis and relative ease of derivitization with functional groups attached on the inside or outside of the polymer [8
]. Programmed degradation of the polymer could result in timely, quantitative delivery of a drug, plasmid or other bioactive molecule.
Computing the magnetically induced mobility of SPION used as therapeutic carriers is important for their clinical applications. Magnetic force calculations aid in the determination of minimum field and magnetic material formulation, both to reduce technology and drug costs, and ensure patient safety. Force characterization is also a step towards determining the velocity of the particles through tissues, which is vital to developing dosing regimens. The equations for these two quantities are [9
Thus, the magnetic force Fm from an external permanent or electromagnet that would be used to pull SPION towards its pole face is dependent upon the field strength H and gradient dH/dy produced by the magnet. This equation can be rewritten in terms of the flux density B and simplified if one is using the CGS unit system, in which free space permeability μ0 is unity and where B is given in Gauss and dB/dy is in Gauss/cm.
The remaining factors are all properties of the SPION, which are the magnetic susceptibility χ (emu per Oe · cm3), the volume fraction of magnetite fm (dimensionless), and the overall particle volume V (cm3). The equation for velocity takes into consideration the drag force experienced by the particle moving through a substance of viscosity η according to Stokes' theorem. This involves determining the particle's radius r. The velocity equation can be further simplified to a function of Fm and viscosity: