Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics
Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1062379/full |
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| author | Erdem Yildiz Erdem Yildiz Anselm J. Gadenstaetter Anselm J. Gadenstaetter Matthias Gerlitz Matthias Gerlitz Lukas D. Landegger Lukas D. Landegger Rudolfs Liepins Michael Nieratschker Michael Nieratschker Rudolf Glueckert Hinrich Staecker Clemens Honeder Clemens Honeder Christoph Arnoldner Christoph Arnoldner |
| author_facet | Erdem Yildiz Erdem Yildiz Anselm J. Gadenstaetter Anselm J. Gadenstaetter Matthias Gerlitz Matthias Gerlitz Lukas D. Landegger Lukas D. Landegger Rudolfs Liepins Michael Nieratschker Michael Nieratschker Rudolf Glueckert Hinrich Staecker Clemens Honeder Clemens Honeder Christoph Arnoldner Christoph Arnoldner |
| author_sort | Erdem Yildiz |
| collection | DOAJ |
| description | Hearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel therapeutics. For such translational research projects, animal models are indispensable, but differences in inner ear dimensions and other anatomical features complicate the transfer of experimental results to the clinic. The gap between rodents and humans may be bridged using larger animal models such as non-human primates. However, their use is challenging and impeded by administrative, regulatory, and financial hurdles. Other large animal models with more human-like inner ear dimensions are scarce. In this study, we analyzed the inner ears of piglets as a potential representative model for the human inner ear and established a surgical approach for intracochlear drug application and subsequent apical sampling. Further, controlled intracochlear delivery of fluorescein isothiocyanate-dextran (FITC-d) was carried out after the insertion of a novel, clinically applicable CE-marked cochlear catheter through the round window membrane. Two, six, and 24 hours after a single injection with this device, the intracochlear FITC-d distribution was determined in sequential perilymph samples. The fluorometrically assessed concentrations two hours after injection were compared to the FITC-d content in control groups, which either had been injected with a simple needle puncture through the round window membrane or the cochlear catheter in combination with a stapes vent hole. Our findings demonstrate not only significantly increased apical FITC-d concentrations when using the cochlear catheter but also higher total concentrations in all perilymph samples. Additionally, the concentration decreased after six and 24 hours and showed a more homogenous distribution compared to shorter observation times. |
| first_indexed | 2024-04-10T05:12:30Z |
| format | Article |
| id | doaj.art-43c3dedc1fc3403ab660f8da12b22341 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-10T05:12:30Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-43c3dedc1fc3403ab660f8da12b223412023-03-09T07:02:46ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-03-011410.3389/fphar.2023.10623791062379Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokineticsErdem Yildiz0Erdem Yildiz1Anselm J. Gadenstaetter2Anselm J. Gadenstaetter3Matthias Gerlitz4Matthias Gerlitz5Lukas D. Landegger6Lukas D. Landegger7Rudolfs Liepins8Michael Nieratschker9Michael Nieratschker10Rudolf Glueckert11Hinrich Staecker12Clemens Honeder13Clemens Honeder14Christoph Arnoldner15Christoph Arnoldner16Christian Doppler Laboratory for Inner Ear Research, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaChristian Doppler Laboratory for Inner Ear Research, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaChristian Doppler Laboratory for Inner Ear Research, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaChristian Doppler Laboratory for Inner Ear Research, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaChristian Doppler Laboratory for Inner Ear Research, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Medical University of Innsbruck, Innsbruck, AustriaDepartment of Otolaryngology, Head and Neck Surgery, University of Kansas School of Medicine, Kansas, KS, United StatesChristian Doppler Laboratory for Inner Ear Research, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaChristian Doppler Laboratory for Inner Ear Research, Department of Otorhinolaryngology, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaDepartment of Otorhinolaryngology, Head and Neck Surgery, Vienna General Hospital, Medical University of Vienna, Vienna, AustriaHearing impairment is the most common sensory disorder in humans, and yet hardly any medications are licensed for the treatment of inner ear pathologies. Intricate pharmacokinetic examinations to better understand drug distribution within this complex organ could facilitate the development of novel therapeutics. For such translational research projects, animal models are indispensable, but differences in inner ear dimensions and other anatomical features complicate the transfer of experimental results to the clinic. The gap between rodents and humans may be bridged using larger animal models such as non-human primates. However, their use is challenging and impeded by administrative, regulatory, and financial hurdles. Other large animal models with more human-like inner ear dimensions are scarce. In this study, we analyzed the inner ears of piglets as a potential representative model for the human inner ear and established a surgical approach for intracochlear drug application and subsequent apical sampling. Further, controlled intracochlear delivery of fluorescein isothiocyanate-dextran (FITC-d) was carried out after the insertion of a novel, clinically applicable CE-marked cochlear catheter through the round window membrane. Two, six, and 24 hours after a single injection with this device, the intracochlear FITC-d distribution was determined in sequential perilymph samples. The fluorometrically assessed concentrations two hours after injection were compared to the FITC-d content in control groups, which either had been injected with a simple needle puncture through the round window membrane or the cochlear catheter in combination with a stapes vent hole. Our findings demonstrate not only significantly increased apical FITC-d concentrations when using the cochlear catheter but also higher total concentrations in all perilymph samples. Additionally, the concentration decreased after six and 24 hours and showed a more homogenous distribution compared to shorter observation times.https://www.frontiersin.org/articles/10.3389/fphar.2023.1062379/fulldrug deliverylarge animal modelpharmacokineticsSNHL = sensorineural hearing lossinner ear catheterpig |
| spellingShingle | Erdem Yildiz Erdem Yildiz Anselm J. Gadenstaetter Anselm J. Gadenstaetter Matthias Gerlitz Matthias Gerlitz Lukas D. Landegger Lukas D. Landegger Rudolfs Liepins Michael Nieratschker Michael Nieratschker Rudolf Glueckert Hinrich Staecker Clemens Honeder Clemens Honeder Christoph Arnoldner Christoph Arnoldner Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics Frontiers in Pharmacology drug delivery large animal model pharmacokinetics SNHL = sensorineural hearing loss inner ear catheter pig |
| title | Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics |
| title_full | Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics |
| title_fullStr | Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics |
| title_full_unstemmed | Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics |
| title_short | Investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics |
| title_sort | investigation of inner ear drug delivery with a cochlear catheter in piglets as a representative model for human cochlear pharmacokinetics |
| topic | drug delivery large animal model pharmacokinetics SNHL = sensorineural hearing loss inner ear catheter pig |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1062379/full |
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