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J Control Release. 2018 Jun 10;279:243-250. doi: 10.1016/j.jconrel.2018.04.028. Epub 2018 Apr 16.

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

Author information

1
Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Blvd, BRB 1220, Philadelphia, PA 19104, USA. Electronic address: kayyali@pennmedicine.upenn.edu.
2
Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Blvd, BRB 1220, Philadelphia, PA 19104, USA. Electronic address: julianw@pennmedicine.upenn.edu.
3
Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Blvd, BRB 1220, Philadelphia, PA 19104, USA. Electronic address: ramseya@pennmedicine.upenn.edu.
4
Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Blvd, BRB 1220, Philadelphia, PA 19104, USA; Department of Pathology, UT Health Science Center, 6431 Fannin St., MSB 2.262, Houston, TX 77030, USA.
5
Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Blvd, BRB 1220, Philadelphia, PA 19104, USA. Electronic address: tiffany.chao@uphs.upenn.edu.
6
Department of Bioengineering, University of Pennsylvania, 240 Skirkanish Hall, 210 S. 33rd St., Philadelphia, PA 19104, USA. Electronic address: atsourk@seas.upenn.edu.
7
Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Blvd, BRB 1220, Philadelphia, PA 19104, USA. Electronic address: bert.omalley@uphs.upenn.edu.
8
Department of Otorhinolaryngology - Head and Neck Surgery, Perelman School of Medicine at the University of Pennsylvania, 421 Curie Blvd, BRB 1220, Philadelphia, PA 19104, USA. Electronic address: lidaqing@pennmedicine.upenn.edu.

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.

KEYWORDS:

Minimally-invasive inner ear biomaterial delivery platform; Noise exposure; Outer hair cell; Prestin; Targeted multifunctional nanoparticles; c-Jun N-terminal kinase (JNK) pathway

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