title: Improved Auditory Nerve Survival with Nanoengineered Supraparticles for Neurotrophin Delivery into the Deafened Cochlea.
abstract: Cochlear implants electrically stimulate spiral ganglion neurons (SGNs) in order to provide speech cues to severe-profoundly deaf patients. In normal hearing cochleae the SGNs depend on endogenous neurotrophins secreted by sensory cells in the organ of Corti for survival. SGNs gradually degenerate following deafness and consequently there is considerable interest in developing clinically relevant strategies to provide exogenous neurotrophins to preserve SGN survival. The present study investigated the safety and efficacy of a drug delivery system for the cochlea using nanoengineered silica supraparticles. In the present study we delivered Brain-derived neurotrophic factor (BDNF) over a period of four weeks and evaluated SGN survival as a measure of efficacy. Supraparticles were bilaterally implanted into the basal turn of cochleae in profoundly deafened guinea pigs. One ear received BDNF-loaded supraparticles and the other ear control (unloaded) supraparticles. After one month of treatment the cochleae were examined histologically. There was significantly greater survival of SGNs in cochleae that received BDNF supraparticles compared to the contralateral control cochleae (repeated measures ANOVA, p = 0.009). SGN survival was observed over a wide extent of the cochlea. The supraparticles were well tolerated within the cochlea with a tissue response that was localised to the site of implantation in the cochlear base. Although mild, the tissue response was significantly greater in cochleae treated with BDNF supraparticles compared to the controls (repeated measures ANOVA, p = 0.003). These data support the clinical potential of this technology particularly as the supraparticles can be loaded with a variety of therapeutic drugs.
authors: The Bionics Institute, 384-388 Albert Street, East Melbourne, Melbourne, Australia.|The Department of Medical Bionics, University of Melbourne, Melbourne, Australia.|Department of Otolaryngology, University of Melbourne, Melbourne, Australia.
authors: Andrew K
authors: http://orcid.org/0000-0001-9715-8784
authors: AK
authors: Wise
authors: Department of Otolaryngology, University of Melbourne, Melbourne, Australia.
authors: Justin
authors: J
authors: Tan
authors: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, the University of Melbourne, Melbourne, Australia.
authors: Yajun
authors: Y
authors: Wang
authors: ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, and the Department of Chemical and Biomolecular Engineering, the University of Melbourne, Melbourne, Australia.
authors: Frank
authors: F
authors: Caruso
authors: The Bionics Institute, 384-388 Albert Street, East Melbourne, Melbourne, Australia.|The Department of Medical Bionics, University of Melbourne, Melbourne, Australia.|Department of Otolaryngology, University of Melbourne, Melbourne, Australia.
authors: Robert K
authors: RK
authors: Shepherd
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D003051:Cochlea / Q000187:drug effects*; D003054:Cochlear Implants; D003056:Cochlear Nerve / Q000187:drug effects* / Q000502:physiology; D003638:Deafness / Q000188:drug therapy*; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D006168:Guinea Pigs; D008297:Male; D053758:Nanoparticles / Q000627:therapeutic use*; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000627:therapeutic use; D013136:Spiral Ganglion / Q000187:drug effects / Q000502:physiology
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors