Intracochlear drug delivery systems: a novel approach whose time has come

Peppi, Marcello; Marie, Aurore; Belline, C; Borenstein, Jeffrey T.

doi:10.1080/17425247.2018.1444026

Cited by 20 publications

(8 citation statements)

References 28 publications

(33 reference statements)

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“…Microfluidic systems, on the other hand, incorporate flexibility of programming drug infusion rates. Advances have been made recently in this area leading to the development of a self-contained, programmable device (Chen et al, 2005; Fiering et al, 2009; Sewell et al, 2009; Peppi et al, 2018). Cochlear infusion of a glutamate receptor antagonist in guinea pigs was achieved for 30 days using a microfluidic system (Fiering et al, 2009).…”

Section: Inner Ear Drug Deliverymentioning

confidence: 99%

Local Drug Delivery for the Treatment of Neurotology Disorders

Piu

Bishop

2019

Front. Cell. Neurosci.

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Neurotology disorders such as vertigo, tinnitus, and hearing loss affect a significant proportion of the population (estimated 39 million in the United States with moderate to severe symptoms). Yet no pharmacological treatments have been developed, in part due to limitations in effective drug delivery to the anatomically protected inner ear compartment. Intratympanic delivery, a minimally invasive injection performed in the office setting, offers a potential direct route of administration. Currently, off-label use of therapeutics approved to treat disorders via systemic administration are being injected intratympanically, mostly in the form of aqueous solutions, but provide variable levels of drug exposure for a limited time requiring repeated injections. Hence, current drug delivery approaches for neurotology disorders are sub-optimal. This review, following a description of pharmacokinetic considerations of the inner ear, explores the merits of novel delivery approaches toward the treatment of neurotology disorders. Methodologies employing local delivery to the inner ear are described, including direct intracochlear delivery as well as intratympanic methods of infusion and injection. Intratympanic injection delivery formulation strategies including hydrogels, polymers and nanoparticulate systems are explored. These approaches represent progress toward more effective delivery options for the clinical treatment of a variety of neurotology disorders.

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Section: Inner Ear Drug Deliverymentioning

confidence: 99%

Local Drug Delivery for the Treatment of Neurotology Disorders

Piu

Bishop

2019

Front. Cell. Neurosci.

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“…The on-going phase I trial of intra-labyrinthine infusion of an adenoviral vector carrying Atonal is the first to use intracochlear delivery in humans (Novartis Pharmaceuticals, 2014;Peppi et al, 2018).…”

Section: Delivery Of Therapeutics To the Inner Earmentioning

confidence: 99%

Early phase trials of novel hearing therapeutics: Avenues and opportunities

Schilder

Mandavia

et al. 2019

Hearing Research

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Novel hearing therapeutics are rapidly progressing along the innovation pathway and into the clinical trial domain. Because these trials are new to the hearing community, they come with challenges in terms of trial design, regulation and delivery. In this paper, we address the key scientific and operational issues and outline the opportunities for interdisciplinary and international collaboration these trials offer. Vital to the future successful implementation of these therapeutics is to evaluate their potential for adoption into healthcare systems, including consideration of their health economic value. This requires early engagement with all stakeholder groups along the hearing innovation pathway.

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“…Local delivery is an attractive option as it overcomes concerns regarding toxicity or side effects associated with systemic administration (Plontke et al, 2014; Salt and Plontke, 2018), allowing higher concentrations to reach the inner ear (Liu et al, 2018). It can be broadly divided into intra-tympanic or intra-cochlear routes, each with many options for delivery method and therapeutic formulation (Liu et al, 2018; Peppi et al, 2018; Salt and Plontke, 2018). Middle ear approaches, such as transtympanic injection, rely on simple diffusion through the epithelial barriers of the round and/or oval window (Salt and Plontke, 2018).…”

Section: Introductionmentioning

confidence: 99%

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

Anderson

Xie

et al. 2019

Front. Cell. Neurosci.

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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.

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Intracochlear drug delivery systems: a novel approach whose time has come

Cited by 20 publications

References 28 publications

Local Drug Delivery for the Treatment of Neurotology Disorders

Local Drug Delivery for the Treatment of Neurotology Disorders

Early phase trials of novel hearing therapeutics: Avenues and opportunities

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

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