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A novel nanoparticle delivery system for targeted therapy of noise-induced hearing loss.

Abstract
Hearing loss is the most prevalent sensory disability worldwide and may be caused by age, drugs or exposure to excessive noise. We have previously developed a minimally-invasive nanohydrogel drug delivery system that successfully delivers nanoparticles into the inner ear. We have substantially extended this technique by functionalizing the nanoparticles and introducing a targeting peptide which recognizes prestin, a transmembrane electromotile protein uniquely expressed in outer hair cells (OHCs) of the inner ear. We demonstrate the successful delivery of molecules and plasmids specifically to OHCs. When compared to untargeted nanoparticles, the delivery of a c-Jun N-terminal kinase (JNK) inhibitor, D-JNKi-1, to OHCs by targeted nanoparticles improved protection from noise induced hearing loss (NIHL). This is the first demonstration of a protection from NIHL using a novel safe and controllable delivery system which is minimally-invasive to the inner ear and, as such, is an extremely appealing technique for use in many clinical applications.
AuthorsMohammad N Kayyali, Julian R A Wooltorton, Andrew J Ramsey, Mei Lin, Tiffany N Chao, Andrew Tsourkas, Bert W O'Malley Jr, Daqing Li
JournalJournal of controlled release : official journal of the Controlled Release Society (J Control Release) Vol. 279 Pg. 243-250 (06 10 2018) ISSN: 1873-4995 [Electronic] Netherlands
PMID29673641 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
CopyrightCopyright © 2018. Published by Elsevier B.V.
Chemical References
  • Neuroprotective Agents
  • Peptides
  • JNK Mitogen-Activated Protein Kinases
  • D-JNKI-1
Topics
  • Animals
  • CHO Cells
  • Cell Line
  • Cricetulus
  • Drug Delivery Systems
  • Ear, Inner (metabolism)
  • Female
  • Hair Cells, Auditory, Outer (metabolism)
  • Hearing Loss, Noise-Induced (drug therapy, physiopathology)
  • Humans
  • JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors)
  • Mice
  • Mice, Inbred CBA
  • Nanoparticles
  • Neuroprotective Agents (administration & dosage, pharmacology)
  • Peptides (administration & dosage, pharmacology)

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