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Abstract Submission Deadline 31 March 2023
Manuscript Submission Deadline 31 July 2023

Despite extensive research on potential therapies for hearing disorders, there are currently no pharmacological or biological interventions approved for hearing loss (HL). HL may result from profound congenital or sensorineural deficits, characterized by degeneration of the sensory hair cells, the primary auditory neurons and their synaptic connection to the hair cells - the ribbon synapse. Research over the last two decades has considerably improved our understanding of cellular and molecular mechanisms that contribute to different forms of HL, but have also brought various innovative therapeutic strategies, including drug, gene and cell therapies. Their development has been challenged by the isolated anatomical position of the inner ear and the presence of the blood-labyrinth barrier (BLB), requiring drug passage across multiple tissue barriers. These particularities lead to innovative approaches to allow a local delivery specific for the inner ear, which are not always suitable for humans.

Systemic administration can be considered for small molecules, being advantageous for repeated treatment and also challenging due to potential side effects and difficulty to cross the BLB. BLB can significantly prevent effective penetration of drugs into the inner ear in appropriate concentrations. To overcome these issues, local delivery in the middle (ME) or inner ear (IE) can be considered. The most common and translational method is the transtympanic administration, enabling higher concentration of drug in the ME that will diffuse into the IE, even after passing several tissue barriers, including the round window membrane. For gene and cell therapies, and in some cases for drugs, a direct delivery in the IE is required, via intracochlear injection or infusion.

Our goal is to provide a complete overview of the routes of administration that have been developed for preclinical studies and to elucidate among them, those that can be translational to clinics. Original research and review papers which address the following broad themes, but are not limited to them, are, therefore, welcome:

- The route of administration that can be used in preclinical models for hearing disorder therapies
- Local delivery in the ME and the IE, including innovative methods, used in preclinical animal model (ME admininistration: Transtympanic injection - single or repeated- or ME infusion; IE delivery intracochlear injection or infusion – canalostomy, cochleostomy or round window)
- Emerging approaches toward safe and efficacious dosing of emerging therapeutic compounds, including the appropriate formulation
- The route of administration related to the kind of therapies: small molecules, large molecules, biological products, gene and cell therapies
- The translational potential of delivery approaches used in preclinical animal models to clinical trials in patients
- The delivery methods in patients, study case for hearing loss, the opportunities during cochlear implant surgery

Dr. Gaëlle Naert is the Chief Operations Officer at CILcare. The other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: hearing loss, hearing disorders, inner ear therapeutics, drug delivery, routes of administration


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Despite extensive research on potential therapies for hearing disorders, there are currently no pharmacological or biological interventions approved for hearing loss (HL). HL may result from profound congenital or sensorineural deficits, characterized by degeneration of the sensory hair cells, the primary auditory neurons and their synaptic connection to the hair cells - the ribbon synapse. Research over the last two decades has considerably improved our understanding of cellular and molecular mechanisms that contribute to different forms of HL, but have also brought various innovative therapeutic strategies, including drug, gene and cell therapies. Their development has been challenged by the isolated anatomical position of the inner ear and the presence of the blood-labyrinth barrier (BLB), requiring drug passage across multiple tissue barriers. These particularities lead to innovative approaches to allow a local delivery specific for the inner ear, which are not always suitable for humans.

Systemic administration can be considered for small molecules, being advantageous for repeated treatment and also challenging due to potential side effects and difficulty to cross the BLB. BLB can significantly prevent effective penetration of drugs into the inner ear in appropriate concentrations. To overcome these issues, local delivery in the middle (ME) or inner ear (IE) can be considered. The most common and translational method is the transtympanic administration, enabling higher concentration of drug in the ME that will diffuse into the IE, even after passing several tissue barriers, including the round window membrane. For gene and cell therapies, and in some cases for drugs, a direct delivery in the IE is required, via intracochlear injection or infusion.

Our goal is to provide a complete overview of the routes of administration that have been developed for preclinical studies and to elucidate among them, those that can be translational to clinics. Original research and review papers which address the following broad themes, but are not limited to them, are, therefore, welcome:

- The route of administration that can be used in preclinical models for hearing disorder therapies
- Local delivery in the ME and the IE, including innovative methods, used in preclinical animal model (ME admininistration: Transtympanic injection - single or repeated- or ME infusion; IE delivery intracochlear injection or infusion – canalostomy, cochleostomy or round window)
- Emerging approaches toward safe and efficacious dosing of emerging therapeutic compounds, including the appropriate formulation
- The route of administration related to the kind of therapies: small molecules, large molecules, biological products, gene and cell therapies
- The translational potential of delivery approaches used in preclinical animal models to clinical trials in patients
- The delivery methods in patients, study case for hearing loss, the opportunities during cochlear implant surgery

Dr. Gaëlle Naert is the Chief Operations Officer at CILcare. The other Topic Editors declare no competing interests with regards to the Research Topic subject.

Keywords: hearing loss, hearing disorders, inner ear therapeutics, drug delivery, routes of administration


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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