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Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders
Middle ear ailments include a broad range of pathological conditions. Otitis media is the leading middle ear disease of childhood, which incurs significant health care resources in developed countries and, in developing countries, causes significant mortality and morbidity. Recurrent and chronic inf...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775502/ https://www.ncbi.nlm.nih.gov/pubmed/33392211 http://dx.doi.org/10.3389/fmed.2020.503819 |
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author | Kurabi, Arwa Cooper, Molly Spriggs, Meghan Xu, Yuge Schaerer, Daniel Ryan, Allen F. |
author_facet | Kurabi, Arwa Cooper, Molly Spriggs, Meghan Xu, Yuge Schaerer, Daniel Ryan, Allen F. |
author_sort | Kurabi, Arwa |
collection | PubMed |
description | Middle ear ailments include a broad range of pathological conditions. Otitis media is the leading middle ear disease of childhood, which incurs significant health care resources in developed countries and, in developing countries, causes significant mortality and morbidity. Recurrent and chronic infections of the middle ear lead to the prolonged presence of inflammatory factors and cellular infiltrates resulting in temporary hearing loss. However, long-term alteration of the middle ear space can pose the risk of permanent damage to the delicate ear structures and cause tissue remodeling. While the etiopathogenesis of middle ear diseases is multifactorial, targeting the biological mechanisms and molecular networks that drive disease development is critical. Yet, a pivotal step in realizing the potential of molecular therapies is the development of methods for local drug delivery, since systemic application risks side effects. Utilizing bacteriophage display in the rat, we discovered rare peptides that are able to transit the intact tympanic membrane from the external canal to the middle ear cavity by an active process. An in vitro assay demonstrated that transport occurs across the tympanic membranes of humans and that the peptides cross the membrane independent of phage. Transport of phage, which is ~900 nm in length, suggests that these peptides could non-invasively deliver drug packages or gene therapy vectors into the middle ear. |
format | Online Article Text |
id | pubmed-7775502 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-77755022021-01-02 Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders Kurabi, Arwa Cooper, Molly Spriggs, Meghan Xu, Yuge Schaerer, Daniel Ryan, Allen F. Front Med (Lausanne) Medicine Middle ear ailments include a broad range of pathological conditions. Otitis media is the leading middle ear disease of childhood, which incurs significant health care resources in developed countries and, in developing countries, causes significant mortality and morbidity. Recurrent and chronic infections of the middle ear lead to the prolonged presence of inflammatory factors and cellular infiltrates resulting in temporary hearing loss. However, long-term alteration of the middle ear space can pose the risk of permanent damage to the delicate ear structures and cause tissue remodeling. While the etiopathogenesis of middle ear diseases is multifactorial, targeting the biological mechanisms and molecular networks that drive disease development is critical. Yet, a pivotal step in realizing the potential of molecular therapies is the development of methods for local drug delivery, since systemic application risks side effects. Utilizing bacteriophage display in the rat, we discovered rare peptides that are able to transit the intact tympanic membrane from the external canal to the middle ear cavity by an active process. An in vitro assay demonstrated that transport occurs across the tympanic membranes of humans and that the peptides cross the membrane independent of phage. Transport of phage, which is ~900 nm in length, suggests that these peptides could non-invasively deliver drug packages or gene therapy vectors into the middle ear. Frontiers Media S.A. 2020-12-18 /pmc/articles/PMC7775502/ /pubmed/33392211 http://dx.doi.org/10.3389/fmed.2020.503819 Text en Copyright © 2020 Kurabi, Cooper, Spriggs, Xu, Schaerer and Ryan. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Medicine Kurabi, Arwa Cooper, Molly Spriggs, Meghan Xu, Yuge Schaerer, Daniel Ryan, Allen F. Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders |
title | Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders |
title_full | Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders |
title_fullStr | Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders |
title_full_unstemmed | Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders |
title_short | Molecular Screening Strategy to Identify a Non-invasive Delivery Mechanism for the Treatment of Middle Ear Disorders |
title_sort | molecular screening strategy to identify a non-invasive delivery mechanism for the treatment of middle ear disorders |
topic | Medicine |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775502/ https://www.ncbi.nlm.nih.gov/pubmed/33392211 http://dx.doi.org/10.3389/fmed.2020.503819 |
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