Recent advances in therapeutics and drug delivery for the treatment of inner ear diseases: a patent review (2011-2015)

ABSTRACT

Introduction: Inner ear disorders such as hearing loss, tinnitus, and Ménière’s disease significantly impact the quality of life of affected individuals. Treatment of such disorders is an ongoing challenge. Current clinical approaches relieve symptoms but do not fully restore hearing, and the search for more effective therapeutic methods represents an area of urgent current interest.

Areas covered: Thirty four patents and patent applications published from 2011 to 2015 were selected from the database of the U.S. Patent and Trademark Office (USPTO) and World Intellectual Property Organization (WIPO), covering new approaches for the treatment of inner ear disorders described in the patent literature: 1) identification of new therapeutic agents, 2) development of sustained release formulations, and 3) medical devices that facilitate delivery of such agents to the inner ear.

Expert opinion: The search for effective treatments of inner ear disorders is ongoing. Increased understanding of the molecular mechanisms of hearing loss, Ménière’s disease, and tinnitus is driving development of new therapeutic agents. However, delivery of these agents to the inner ear is a continuing challenge. At present, combination of a suitable drug with an appropriate mode of drug delivery is the key focus of innovative research to cure inner ear disorders.

KEYWORDS:

• Hearing loss
• tinnitus
• Ménière’s disease
• inner ear disorders
• ototoxicity
• local drug delivery
• sustained drug delivery
• hair cell regeneration
• hair cell protection

Article highlights

• Common inner ear disorders (e.g., hearing loss, Ménière’s disease, and tinnitus) affect a significant portion of the world population. Currently available treatments generally mitigate symptoms but do not fully restore hearing in patients with high level of success.

• Using either high throughput screening or examination of well-known, FDA approved drugs for use to treat other diseases (e.g., S-ketamine, gacyclidine, etc.), to target receptors involved in the mechanisms of inner ear disorders, researchers have identified potent compounds, several of which have been developed as lead compounds now under evaluation in clinical trials

• Local delivery of drugs of interest has important advantages for the treatment of inner ear disorders, offering precision of dose and avoidance of possible adverse effects associated with systemic administration.

• Though novel formulations of drugs with hydrogels (e.g., hyaluronic acid, chitosan, and poloxamer 407) allow the sustained release of drugs, this process still relies mainly on passive diffusion.

• Novel design of medical devices potentially offers solutions in facilitating drug delivery to the inner ear in a well-regulated manner.

• There remains ample scope for further innovation in this promising emerging area with the future challenges of personalized medicine for otological disorders also likely to require the invention of new localized drug delivery technologies.

This box summarizes key points contained in the article.

Acknowledgments

The authors would like to thank Ms. Inah Kang for her assistance in preparing this manuscript.

Declaration of interest

JS Kempfle was involved as an inventor on the patent application US 20150209406A1 [35]. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was funded by the Herbert Silverstein Award from the American Neurotology Society (DJ) and by the USC Dornsife College of Letters, Arts and Sciences (KN, CEMcK).