Superparamagnetic‐PLGA non‐viral vectors for inner ear therapy

Loss of auditory hair cells (deafness) is the major sensory disability. Mammalian hair cells neither repair nor regenerate, but hearing restoration by adenoviral gene therapy of cochlear supporting cells was recently proven. Math‐1 transfection using a non‐viral polymeric, magnetically susceptible nanoparticle vector is this study goal. Superparamagnetic iron oxide nanoparticles (SPION) coated with oleic acid, were encapsulated into poly(D,Llactide‐co‐glycolide) (PLGA). Particle size (dynamic light scattering) varied from 160 nm to 280 nm while zeta potential remained near −20 mV. Transmission electron microscopy showed SPION uniformly encapsulated in PLGA with diameters of 5 to 15 nm. PLGA‐SPION composite nanoparticles were pulled by external magnetic field and gradient through the round window membrane of guinea pigs and cadavers, and into various cell cultures, confirmed by transmission electron or confocal microscopy. When nanoparticles were infused into the cochlea, particles also were found in the organ of Corti. Magnetic targeting resulted in particles delivered to the round window membrane, perilymph and cochlear basal turn (basilar membrane, and stria vascularis). The results suggest nanoparticle non‐viral vectors can deliver Math‐1 and therapeutic biomolecules into the cochlea across the round window membrane using an external magnetic field.