Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ

Background and Introduction: Acute otitis media is the most common reason for a visit to the pediatrician, often requiring systemic administration of oral antibiotics. Local drug therapy applied to the middle ear could avoid side effects associated with systemic antibiotic administration, however in...

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Main Authors: Samuel Early, Rong Yang, Xiyu Li, Zipei Zhang, Jens C. van der Valk, Xiaojie Ma, Daniel S. Kohane, Konstantina M. Stankovic
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-02-01
Series:Frontiers in Neurology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2021.580392/full
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author Samuel Early
Samuel Early
Samuel Early
Rong Yang
Rong Yang
Xiyu Li
Zipei Zhang
Jens C. van der Valk
Jens C. van der Valk
Jens C. van der Valk
Xiaojie Ma
Xiaojie Ma
Xiaojie Ma
Daniel S. Kohane
Konstantina M. Stankovic
Konstantina M. Stankovic
Konstantina M. Stankovic
Konstantina M. Stankovic
spellingShingle Samuel Early
Samuel Early
Samuel Early
Rong Yang
Rong Yang
Xiyu Li
Zipei Zhang
Jens C. van der Valk
Jens C. van der Valk
Jens C. van der Valk
Xiaojie Ma
Xiaojie Ma
Xiaojie Ma
Daniel S. Kohane
Konstantina M. Stankovic
Konstantina M. Stankovic
Konstantina M. Stankovic
Konstantina M. Stankovic
Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ
Frontiers in Neurology
otitis media
antibiotic
permeability
temporal bone
permeability enhancers
tympanic membrane
author_facet Samuel Early
Samuel Early
Samuel Early
Rong Yang
Rong Yang
Xiyu Li
Zipei Zhang
Jens C. van der Valk
Jens C. van der Valk
Jens C. van der Valk
Xiaojie Ma
Xiaojie Ma
Xiaojie Ma
Daniel S. Kohane
Konstantina M. Stankovic
Konstantina M. Stankovic
Konstantina M. Stankovic
Konstantina M. Stankovic
author_sort Samuel Early
title Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ
title_short Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ
title_full Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ
title_fullStr Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ
title_full_unstemmed Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In Situ
title_sort initial method for characterization of tympanic membrane drug permeability in human temporal bones in situ
publisher Frontiers Media S.A.
series Frontiers in Neurology
issn 1664-2295
publishDate 2021-02-01
description Background and Introduction: Acute otitis media is the most common reason for a visit to the pediatrician, often requiring systemic administration of oral antibiotics. Local drug therapy applied to the middle ear could avoid side effects associated with systemic antibiotic administration, however in the majority of patients this would require drugs to diffuse across an intact tympanic membrane. Experimental methods for testing trans-tympanic drug flux in human tissues in situ would be highly valuable to guide drug therapy development for local drug delivery to the middle ear.Materials and Methods: A total of 30 cadaveric human temporal bones were characterized by trans-tympanic impedance testing to determine how steps in tissue processing and storage might impact intactness of the tympanic membrane and thus suitability for use in studies of trans-tympanic drug flux. Ciprofloxacin drug solutions of varying concentrations were then applied to the lateral surface of the tympanic membrane in eight samples, and middle ear aspirate was collected over the following 48 h to evaluate trans-tympanic flux to the middle ear.Results: Tissue processing steps that involved extensive tissue manipulation were consistently associated with evidence of microperforations in the tympanic membrane tissue. Maintaining the tympanic membrane in situ within the temporal bone, while using an otologic drill to obtain transmastoid access to the middle ear, was demonstrated as a reliable, non-damaging technique for accessing both lateral and medial surfaces for trans-tympanic flux testing. Results in these bones demonstrated trans-tympanic flux of ciprofloxacin when administered at sufficiently high concentration.Discussion and Conclusion: The study describes key techniques and best practices, as well as pitfalls to avoid, in the development of a model for studying trans-tympanic drug flux in human temporal bones in situ. This model can be a valuable research tool in advancing progress toward eventual clinical studies for trans-tympanic drug delivery to the middle ear.
topic otitis media
antibiotic
permeability
temporal bone
permeability enhancers
tympanic membrane
url https://www.frontiersin.org/articles/10.3389/fneur.2021.580392/full
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spelling doaj-946437698f2b4973a025366672dc490c2021-02-23T05:03:33ZengFrontiers Media S.A.Frontiers in Neurology1664-22952021-02-011210.3389/fneur.2021.580392580392Initial Method for Characterization of Tympanic Membrane Drug Permeability in Human Temporal Bones In SituSamuel Early0Samuel Early1Samuel Early2Rong Yang3Rong Yang4Xiyu Li5Zipei Zhang6Jens C. van der Valk7Jens C. van der Valk8Jens C. van der Valk9Xiaojie Ma10Xiaojie Ma11Xiaojie Ma12Daniel S. Kohane13Konstantina M. Stankovic14Konstantina M. Stankovic15Konstantina M. Stankovic16Konstantina M. Stankovic17Eaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesSchool of Medicine, University of California, San Diego, San Diego, CA, United StatesLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, United StatesRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY, United StatesLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, United StatesLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesLeiden University Medical Center, Leiden, NetherlandsEaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesDepartment of Otolaryngology, Qilu Hospital of Shandong University, Jinan, ChinaLaboratory for Biomaterials and Drug Delivery, Department of Anesthesiology, Division of Critical Care Medicine, Children's Hospital Boston, Harvard Medical School, Boston, MA, United StatesEaton-Peabody Laboratories, Department of Otolaryngology – Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United StatesDepartment of Otolaryngology – Head and Neck Surgery, Harvard Medical School, Boston, MA, United StatesProgram in Speech and Hearing Bioscience and Technology, Harvard Medical School, Boston, MA, United StatesHarvard Program in Therapeutic Science, Harvard Medical School, Boston, MA, United StatesBackground and Introduction: Acute otitis media is the most common reason for a visit to the pediatrician, often requiring systemic administration of oral antibiotics. Local drug therapy applied to the middle ear could avoid side effects associated with systemic antibiotic administration, however in the majority of patients this would require drugs to diffuse across an intact tympanic membrane. Experimental methods for testing trans-tympanic drug flux in human tissues in situ would be highly valuable to guide drug therapy development for local drug delivery to the middle ear.Materials and Methods: A total of 30 cadaveric human temporal bones were characterized by trans-tympanic impedance testing to determine how steps in tissue processing and storage might impact intactness of the tympanic membrane and thus suitability for use in studies of trans-tympanic drug flux. Ciprofloxacin drug solutions of varying concentrations were then applied to the lateral surface of the tympanic membrane in eight samples, and middle ear aspirate was collected over the following 48 h to evaluate trans-tympanic flux to the middle ear.Results: Tissue processing steps that involved extensive tissue manipulation were consistently associated with evidence of microperforations in the tympanic membrane tissue. Maintaining the tympanic membrane in situ within the temporal bone, while using an otologic drill to obtain transmastoid access to the middle ear, was demonstrated as a reliable, non-damaging technique for accessing both lateral and medial surfaces for trans-tympanic flux testing. Results in these bones demonstrated trans-tympanic flux of ciprofloxacin when administered at sufficiently high concentration.Discussion and Conclusion: The study describes key techniques and best practices, as well as pitfalls to avoid, in the development of a model for studying trans-tympanic drug flux in human temporal bones in situ. This model can be a valuable research tool in advancing progress toward eventual clinical studies for trans-tympanic drug delivery to the middle ear.https://www.frontiersin.org/articles/10.3389/fneur.2021.580392/fullotitis mediaantibioticpermeabilitytemporal bonepermeability enhancerstympanic membrane