Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Kurabi, Arwa, Cooper, Molly, Spriggs, Meghan, Xu, Yuge, Schaerer, Daniel, Ryan, Allen F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
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
_version_ 1783630481326080000
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
work_keys_str_mv AT kurabiarwa molecularscreeningstrategytoidentifyanoninvasivedeliverymechanismforthetreatmentofmiddleeardisorders
AT coopermolly molecularscreeningstrategytoidentifyanoninvasivedeliverymechanismforthetreatmentofmiddleeardisorders
AT spriggsmeghan molecularscreeningstrategytoidentifyanoninvasivedeliverymechanismforthetreatmentofmiddleeardisorders
AT xuyuge molecularscreeningstrategytoidentifyanoninvasivedeliverymechanismforthetreatmentofmiddleeardisorders
AT schaererdaniel molecularscreeningstrategytoidentifyanoninvasivedeliverymechanismforthetreatmentofmiddleeardisorders
AT ryanallenf molecularscreeningstrategytoidentifyanoninvasivedeliverymechanismforthetreatmentofmiddleeardisorders