title: 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.
authors.affiliation: Hough Ear Institute, Oklahoma City, OK 73112, USA. rkopke@houghearinstitute.com
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kopke
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Wassel
authors.forename: Fadee
authors.initials: F
authors.lastname: Mondalek
authors.forename: Brian
authors.initials: B
authors.lastname: Grady
authors.forename: Kejian
authors.initials: K
authors.lastname: Chen
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Liu
authors.forename: Don
authors.initials: D
authors.lastname: Gibson
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Dormer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D048708:Cell Growth Processes; D002478:Cells, Cultured; D004427:Ear Diseases / Q000534:rehabilitation*; D004574:Electromagnetic Fields; D004578:Electron Spin Resonance Spectroscopy; D052203:Ferrosoferric Oxide; D006168:Guinea Pigs; D006801:Humans; D008422:Materials Testing; D051379:Mice; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D049329:Nanostructures; D009925:Organ of Corti / Q000502:physiology; D009998:Ossicular Prosthesis; D010498:Perilymph / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013701:Temporal Bone / Q000502:physiology
chemical_list: D001672:Biocompatible Materials; D052203:Ferrosoferric Oxide