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Assessment of drug permeability through an ex vivo porcine round window membrane model

Delivery of pharmaceutical therapeutics to the inner ear to treat and prevent hearing loss is challenging. Systemic delivery is not effective as only a small fraction of the therapeutic agent reaches the inner ear. Invasive surgeries to inject through the round window membrane (RWM) or cochleostomy...

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Autores principales: Moatti, Adele, Silkstone, Dylan, Martin, Taylor, Abbey, Keith, Hutson, Kendall A, Fitzpatrick, Douglas C, Zdanski, Carlton J, Cheng, Alan G, Ligler, Frances S, Greenbaum, Alon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197016/
https://www.ncbi.nlm.nih.gov/pubmed/37213232
http://dx.doi.org/10.1016/j.isci.2023.106789
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author Moatti, Adele
Silkstone, Dylan
Martin, Taylor
Abbey, Keith
Hutson, Kendall A
Fitzpatrick, Douglas C
Zdanski, Carlton J
Cheng, Alan G
Ligler, Frances S
Greenbaum, Alon
author_facet Moatti, Adele
Silkstone, Dylan
Martin, Taylor
Abbey, Keith
Hutson, Kendall A
Fitzpatrick, Douglas C
Zdanski, Carlton J
Cheng, Alan G
Ligler, Frances S
Greenbaum, Alon
author_sort Moatti, Adele
collection PubMed
description Delivery of pharmaceutical therapeutics to the inner ear to treat and prevent hearing loss is challenging. Systemic delivery is not effective as only a small fraction of the therapeutic agent reaches the inner ear. Invasive surgeries to inject through the round window membrane (RWM) or cochleostomy may cause damage to the inner ear. An alternative approach is to administer drugs into the middle ear using an intratympanic injection, with the drugs primarily passing through the RWM to the inner ear. However, the RWM is a barrier, only permeable to a small number of molecules. To study and enhance the RWM permeability, we developed an ex vivo porcine RWM model, similar in structure and thickness to the human RWM. The model is viable for days, and drug passage can be measured at multiple time points. This model provides a straightforward approach to developing effective and non-invasive delivery methods to the inner ear.
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spelling pubmed-101970162023-05-20 Assessment of drug permeability through an ex vivo porcine round window membrane model Moatti, Adele Silkstone, Dylan Martin, Taylor Abbey, Keith Hutson, Kendall A Fitzpatrick, Douglas C Zdanski, Carlton J Cheng, Alan G Ligler, Frances S Greenbaum, Alon iScience Article Delivery of pharmaceutical therapeutics to the inner ear to treat and prevent hearing loss is challenging. Systemic delivery is not effective as only a small fraction of the therapeutic agent reaches the inner ear. Invasive surgeries to inject through the round window membrane (RWM) or cochleostomy may cause damage to the inner ear. An alternative approach is to administer drugs into the middle ear using an intratympanic injection, with the drugs primarily passing through the RWM to the inner ear. However, the RWM is a barrier, only permeable to a small number of molecules. To study and enhance the RWM permeability, we developed an ex vivo porcine RWM model, similar in structure and thickness to the human RWM. The model is viable for days, and drug passage can be measured at multiple time points. This model provides a straightforward approach to developing effective and non-invasive delivery methods to the inner ear. Elsevier 2023-05-02 /pmc/articles/PMC10197016/ /pubmed/37213232 http://dx.doi.org/10.1016/j.isci.2023.106789 Text en © 2023 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Moatti, Adele
Silkstone, Dylan
Martin, Taylor
Abbey, Keith
Hutson, Kendall A
Fitzpatrick, Douglas C
Zdanski, Carlton J
Cheng, Alan G
Ligler, Frances S
Greenbaum, Alon
Assessment of drug permeability through an ex vivo porcine round window membrane model
title Assessment of drug permeability through an ex vivo porcine round window membrane model
title_full Assessment of drug permeability through an ex vivo porcine round window membrane model
title_fullStr Assessment of drug permeability through an ex vivo porcine round window membrane model
title_full_unstemmed Assessment of drug permeability through an ex vivo porcine round window membrane model
title_short Assessment of drug permeability through an ex vivo porcine round window membrane model
title_sort assessment of drug permeability through an ex vivo porcine round window membrane model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10197016/
https://www.ncbi.nlm.nih.gov/pubmed/37213232
http://dx.doi.org/10.1016/j.isci.2023.106789
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