CONCLUSION: Silica nanoparticles may serve as a nonviral delivery system to the sensory hair cells, spiral ganglion cells within the cochlea, and the vestibular organ, as well as the cochlear nucleus. OBJECTIVES: At present there are no targeted therapeutics for inner ear disease. A variety of viral vector systems have been tested in the inner ear with variable efficacy but they are still not regarded as safe systems for inner ear delivery. Nanoparticles are a nonviral method of delivering a variety of macromolecules that potentially can be used for delivery within the auditory system. In this study, we evaluated the distribution and safety of nanoparticles in the inner ear. MATERIALS AND METHODS: Cy3-labeled silica nanoparticles were placed on the round window membrane of adult mice. Hearing thresholds were determined after nanoparticle delivery by auditory brainstem responses (ABRs). Distribution of particles was determined by histological evaluation of the cochlea, vestibular organs, and brain stem. RESULTS: Fluorescent microscopy demonstrated Cy3-labeled nanoparticles signals in the sensory hair cells and the spiral ganglion neurons of both the treated and contralateral inner ears. Additionally, the distal part of the central auditory pathway (dorsal cochlear nucleus, superior olivary complex) was found to be labeled with the Cy3-linked silica nanoparticles, indicating a retrograde axonal transport. No hearing loss or inflammation was noted in the treated cochlea.
CONCLUSION:Silica nanoparticles may serve as a nonviral delivery system to the sensory hair cells, spiral ganglion cells within the cochlea, and the vestibular organ, as well as the cochlear nucleus. OBJECTIVES: At present there are no targeted therapeutics for inner ear disease. A variety of viral vector systems have been tested in the inner ear with variable efficacy but they are still not regarded as safe systems for inner ear delivery. Nanoparticles are a nonviral method of delivering a variety of macromolecules that potentially can be used for delivery within the auditory system. In this study, we evaluated the distribution and safety of nanoparticles in the inner ear. MATERIALS AND METHODS:Cy3-labeled silica nanoparticles were placed on the round window membrane of adult mice. Hearing thresholds were determined after nanoparticle delivery by auditory brainstem responses (ABRs). Distribution of particles was determined by histological evaluation of the cochlea, vestibular organs, and brain stem. RESULTS: Fluorescent microscopy demonstrated Cy3-labeled nanoparticles signals in the sensory hair cells and the spiral ganglion neurons of both the treated and contralateral inner ears. Additionally, the distal part of the central auditory pathway (dorsal cochlear nucleus, superior olivary complex) was found to be labeled with the Cy3-linked silica nanoparticles, indicating a retrograde axonal transport. No hearing loss or inflammation was noted in the treated cochlea.
Authors: Victor H Hernandez; Anna Gehrt; Kirsten Reuter; Zhizi Jing; Marcus Jeschke; Alejandro Mendoza Schulz; Gerhard Hoch; Matthias Bartels; Gerhard Vogt; Carolyn W Garnham; Hiromu Yawo; Yugo Fukazawa; George J Augustine; Ernst Bamberg; Sebastian Kügler; Tim Salditt; Livia de Hoz; Nicola Strenzke; Tobias Moser Journal: J Clin Invest Date: 2014-02-10 Impact factor: 14.808
Authors: Badanavalu M Prabhu; Syed F Ali; Richard C Murdock; Saber M Hussain; Malathi Srivatsan Journal: Nanotoxicology Date: 2010-06-01 Impact factor: 5.913
Authors: Andrew A McCall; Erin E Leary Swan; Jeffrey T Borenstein; William F Sewell; Sharon G Kujawa; Michael J McKenna Journal: Ear Hear Date: 2010-04 Impact factor: 3.570
Authors: Erin E Leary Swan; Mark J Mescher; William F Sewell; Sarah L Tao; Jeffrey T Borenstein Journal: Adv Drug Deliv Rev Date: 2008-09-21 Impact factor: 15.470