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

Abstract

Superparamagnetic iron oxide nanoparticles (SNP) composed of magnetite (Fe₃O₄) 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.

Factors influencing the efficacy of round window dexamethasone protection of residual hearing post-cochlear implant surgery

“…While the release profile has not yet been fully characterized, previous work in our laboratories has shown dexamethasone and its breakdown products for a period of no more than 24 h as estimated by perilymph sampling in vivo (James et al, 2008). Other local delivery strategies are currently under investigation, but all have potential short-comings that await further study (Borenstein et al, 2007;Chen et al, 2005;Kopke et al, 2006). These methods include drug-eluting electrode array, use of microinjection and micro-osmotic pump (Borkholder, 2008).…”

Simulation of Application Strategies for Local Drug Delivery to the Inner Ear

“…The carrier would release the drug it was loaded with either through biodegradation or diffusion out of the carrier, a process which could be modulated by external physical stimuli. Other solutions to drug targeting could include immunological methods (using antibodies to direct a drug to a specific cell type) or using magnetic nanospheres [26] , the dispersal of which can be influenced by external magnetic fields.…”

Current Status and Prospects of Gene Therapy for the Inner Ear

“…This approach allows for precise control over the composition, size, and multifunctionality of the gene delivery system. A vector with superparamagnetic iron oxide nanoparticles (SNP) composed of magnetite (Fe 3 O 4 ) for therapeutic molecule delivery into the inner ear of rats has been reported (Kopke et al, 2006). The embedded SNPs, coated with either dextran, silica, or poly(d,l-lactide-coglycolide), were placed in the round window membrane (RWM) niche of the rat.…”