Abstract
BackgroundTo quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION). Flux densities, gradients, and nanoparticle properties were measured in order to quantify the magnetic force on the SPION in both an artificial cochlear round window membrane (RWM) model and the guinea pig RWM.MethodsThree-dimensional maps were created for flux density and magnetic gradient produced by a 24-well casing of 4.1 kilo-Gauss neodymium-iron-boron (NdFeB) disc magnets. The casing was used to pull SPION through a three-layer cell culture RWM model. Similar maps were created for a 4 inch (10.16 cm) cube 48 MGOe NdFeB magnet used to pull polymeric-nanoparticles through the RWM of anesthetized guinea pigs. Other parameters needed to compute magnetic force were nanoparticle and polymer properties, including average radius, density, magnetic susceptibility, and volume fraction of magnetite.ResultsA minimum force of 5.04 × 10-16 N was determined to adequately pull nanoparticles through the in-vitro model. For the guinea pig RWM, the magnetic force on the polymeric nanoparticles was 9.69 × 10-20 N. Electron microscopy confirmed the movement of the particles through both RWM models.ConclusionAs prospective carriers of therapeutic substances, polymers containing superparamagnetic iron oxide nanoparticles were succesfully pulled through the live RWM. The force required to achieve in vivo transport was significantly lower than that required to pull nanoparticles through the in-vitro RWM model. Indeed very little force was required to accomplish measurable delivery of polymeric-SPION composite nanoparticles across the RWM, suggesting that therapeutic delivery to the inner ear by SPION is feasible.
Highlights
To quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION)
The first study utilized data from a round window membrane (RWM) model made of Madin-Darby Canine Kidney (MDCK) cells
The flux density plots created in MatLab® for the 24-well magnet casing and cube magnet are shown in Figures 2 through 5, in both mesh and contour format
Summary
To quantitatively compare in-vitro and in vivo membrane transport studies of targeted delivery, one needs characterization of the magnetically-induced mobility of superparamagnetic iron oxide nanoparticles (SPION). 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. 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
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