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. 2019 Oct 9:13:418.
doi: 10.3389/fncel.2019.00418. eCollection 2019.

Local Delivery of Therapeutics to the Inner Ear: The State of the Science

Caroline R Anderson  1   2 , Carol Xie  1   2 , Matthew P Su  1   2 , Maria Garcia  1   2 , Helen Blackshaw  1   2 , Anne G M Schilder  1   2
Affiliations

Local Delivery of Therapeutics to the Inner Ear: The State of the Science

Caroline R Anderson et al. Front Cell Neurosci. .

Abstract

Background: Advances in the understanding of the genetic and molecular etiologies of inner ear disorders have enabled the identification of therapeutic targets and innovative delivery approaches to the inner ear. As this field grows, the need for knowledge about effective delivery of therapeutics to the inner ear has become a priority. This review maps all clinical and pre-clinical research published in English in the field to date, to guide both researchers and clinicians about local drug delivery methods in the context of novel therapeutics. Methods: A systematic search was conducted using customized strategies in Cochrane, pubmed and EMBASE databases from inception to 30/09/2018. Two researchers undertook study selection and data extraction independently. Results: Our search returned 12,200 articles, of which 837 articles met the inclusion criteria. 679 were original research and 158 were reviews. There has been a steady increase in the numbers of publications related to inner ear therapeutics delivery over the last three decades, with a sharp rise over the last 2 years. The intra-tympanic route accounts for over 70% of published articles. Less than one third of published research directly assesses delivery efficacy, with most papers using clinical efficacy as a surrogate marker. Conclusion: Research into local therapeutic delivery to the inner ear has undergone a recent surge, improving our understanding of how novel therapeutics can be delivered. Direct assessment of delivery efficacy is challenging, especially in humans, and progress in this area is key to understanding how to make decisions about delivery of novel hearing therapeutics.

Keywords: drug delivery; inner ear; intracochlear; intratympanic; novel therapeutics; systematic review.

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Figures

Figure 1
Figure 1
Schematic figure summarizing the structure of the inner ear and delivery routes.
Figure 2
Figure 2
Flow diagram of search results.
Figure 3
Figure 3
Trends in publication of studies on local delivery to the inner ear. (A) Publications per 5 years by study type (original research or review). (B) Original research publications of per 5 years by method of assessment of delivery efficacy (direct assessment via pharmacokinetics or indirect assessment via functional effects, excluding feasibility studies where delivery efficacy is not assessed). (C) Original research publications per 5 years by intratympanic and intracochlea delivery routes in both humans and animals (excluding “other” delivery routes). (D) Original research publications per 5 years by therapeutic class (clinically used small molecule, experimental small molecule, or biopharmaceutical) in both humans and animals. [n.b. (A–D) runs from top to bottom of figure panel].
See this image and copyright information in PMC

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