Bile Is a Selective Elevator for Mucosal Mechanics and Transport

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, leadin...

Celý popis

Uložené v:
Podrobná bibliografia
Vydané v:Molecular pharmaceutics Ročník 20; číslo 12; s. 6151
Hlavní autori: Hanio, Simon, Möllmert, Stephanie, Möckel, Conrad, Choudhury, Susobhan, Höpfel, Andreas I, Zorn, Theresa, Endres, Sebastian, Schlauersbach, Jonas, Scheller, Lena, Keßler, Christoph, Scherf-Clavel, Oliver, Bellstedt, Peter, Schubert, Ulrich S, Pöppler, Ann-Christin, Heinze, Katrin G, Guck, Jochen, Meinel, Lorenz
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 04.12.2023
Predmet:
Animals
Bile
Elevators and Escalators
Mucins
Mucus
Perphenazine
Rats
NMR
diffusion
predictive algorithm
bioavailability
FCS
Brillouin microscopy
differential dynamic microscopy
drug
ISSN:1543-8392, 1543-8392
On-line prístup:Zistit podrobnosti o prístupe
Tagy: Pridať tag
Žiadne tagy, Buďte prvý, kto otaguje tento záznam!
Popis
Shrnutí: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.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1543-8392
1543-8392
DOI:10.1021/acs.molpharmaceut.3c00550