Magnetic Nanoparticles: Inner Ear Targeted Molecule Delivery and Middle Ear Implant

Abstract

Superparamagnetic iron oxide nanoparticles (SNP) composed of magnetite (Fe(3)O(4)) were studied preliminarily as vehicles for therapeutic molecule delivery to the inner ear and as a middle ear implant capable of producing biomechanically relevant forces for auditory function. Magnetite SNP were synthesized, then encapsulated in either silica or poly (D,L,-Lactide-co-glycolide) or obtained commercially with coatings of oleic acid or dextran. Permanent magnetic fields generated forces sufficient to pull them across tissue in several round window membrane models (in vitrocell culture, in vivo rat and guinea pig, and human temporal bone) or to embed them in middle ear epithelia. Biocompatibility was investigated by light and electron microscopy, cell culture kinetics, and hair cell survival in organotypic cell culture and no measurable toxicity was found. A sinusoidal magnetic field applied to guinea pigs with SNP implanted in the middle ear resulted in displacements of the middle ear comparable to 90 dB SPL.