Bile Is a Selective Elevator for Mucosal Mechanics and TransportClick to copy article linkArticle link copied!
- Simon HanioSimon HanioInstitute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Simon Hanio
- Stephanie MöllmertStephanie MöllmertMax Planck Institute for the Science of Light and Max-Planck-Zentrum für Physik und Medizin, Staudtstrasse 2, 91058 Erlangen, GermanyMore by Stephanie Möllmert
- Conrad MöckelConrad MöckelMax Planck Institute for the Science of Light and Max-Planck-Zentrum für Physik und Medizin, Staudtstrasse 2, 91058 Erlangen, GermanyMore by Conrad Möckel
- Susobhan ChoudhurySusobhan ChoudhuryRudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, GermanyMore by Susobhan Choudhury
- Andreas I. HöpfelAndreas I. HöpfelRudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, GermanyMore by Andreas I. Höpfel
- Theresa ZornTheresa ZornInstitute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Theresa Zorn
- Sebastian EndresSebastian EndresInstitute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Sebastian Endres
- Jonas SchlauersbachJonas SchlauersbachInstitute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Jonas Schlauersbach
- Lena SchellerLena SchellerInstitute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Lena Scheller
- Christoph KeßlerChristoph KeßlerInstitute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Christoph Keßler
- Oliver Scherf-ClavelOliver Scherf-ClavelInstitute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Oliver Scherf-Clavel
- Peter BellstedtPeter BellstedtInstitute of Organic Chemistry, University of Jena, Humboldtstrasse 10, 07743 Jena, GermanyInstitute for Clinical Chemistry, University of Zürich,Rämistrasse 100, 8091 Zurich, SwitzerlandMore by Peter Bellstedt
- Ulrich S. SchubertUlrich S. SchubertInstitute of Organic Chemistry, University of Jena, Humboldtstrasse 10, 07743 Jena, GermanyJena Center for Soft Matter (JCSM), University of Jena, Philosophenweg 7, 07743 Jena, GermanyMore by Ulrich S. Schubert
- Ann-Christin PöpplerAnn-Christin PöpplerInstitute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Wuerzburg, GermanyMore by Ann-Christin Pöppler
- Katrin G. HeinzeKatrin G. HeinzeRudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Josef-Schneider-Str. 2, 97080 Wuerzburg, GermanyMore by Katrin G. Heinze
- Jochen Guck*Jochen Guck*Email: [email protected]Max Planck Institute for the Science of Light and Max-Planck-Zentrum für Physik und Medizin, Staudtstrasse 2, 91058 Erlangen, GermanyMore by Jochen Guck
- Lorenz Meinel*Lorenz Meinel*Email: [email protected]Institute for Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, GermanyHelmholtz Institute for RNA-based Infection Research (HIRI), Josef-Schneider-Strasse 2, 97080 Wuerzburg, GermanyMore by Lorenz Meinel
Abstract
Mucus mechanically protects the intestinal epithelium and impacts the absorption of drugs, with a largely unknown role for bile. We explored the impacts of bile on mucosal biomechanics and drug transport within mucus. Bile diffused with square-root-of-time kinetics and interplayed with mucus, leading to transient stiffening captured in Brillouin images and a concentration-dependent change from subdiffusive to Brownian-like diffusion kinetics within the mucus demonstrated by differential dynamic microscopy. Bile-interacting drugs, Fluphenazine and Perphenazine, diffused faster through mucus in the presence of bile, while Metoprolol, a drug with no bile interaction, displayed consistent diffusion. Our findings were corroborated by rat studies, where co-dosing of a bile acid sequestrant substantially reduced the bioavailability of Perphenazine but not Metoprolol. We clustered over 50 drugs based on their interactions with bile and mucin. Drugs that interacted with bile also interacted with mucin but not vice versa. This study detailed the dynamics of mucus biomechanics under bile exposure and linked the ability of a drug to interact with bile to its abbility to interact with mucus.
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