Journal ArticleDOI
In vitro models of the intestinal barrier. The report and recommendations of ECVAM Workshop 46. European Centre for the Validation of Alternative methods.
Eric Le Ferrec,Christophe Chesne,Per Artusson,David J. Brayden,Gérard Fabre,Pierre Gires,François Guillou,Monique Rousset,Werner Rubas,Maria-Laura Scarino +9 more
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The main aims of the workshop were to seek a consensus on the current models of the intestinal barriers and ways to screen for the movement of drugs across this barrier, and to make useful recommendations for the promotion of the three Rs in this area as discussed by the authors.Abstract:
The principal aims of the workshop were to seek a consensus on the current models of the intestinal barriers and ways to screen for the movement of drugs across this barrier,and to make useful recommendations for the promotion of the three Rs in this area.read more
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Journal ArticleDOI
TEER Measurement Techniques for In Vitro Barrier Model Systems
Balaji Srinivasan,Aditya Reddy Kolli,Mandy B. Esch,Hasan E. Abaci,Michael L. Shuler,James J. Hickman +5 more
TL;DR: The aim of this article is to review the different TEER measurement techniques and analyze their strengths and weaknesses, determine the significance of TEER in drug toxicity studies, and examine the various in vitro models and microfluidic organs-on-chips implementations using TEER measurements in some widely studied barrier models.
Journal ArticleDOI
Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow
Hyun Jung Kim,Dongeun Huh,Geraldine A. Hamilton,Donald E. Ingber,Donald E. Ingber,Donald E. Ingber +5 more
TL;DR: This gut-on-a-chip recapitulates multiple dynamic physical and functional features of human intestine that are critical for its function within a controlled microfluidic environment that is amenable for transport, absorption, and toxicity studies, and hence it should have great value for drug testing as well as development of novel intestinal disease models.
Journal ArticleDOI
A four-organ-chip for interconnected long-term co-culture of human intestine, liver, skin and kidney equivalents
Ilka Maschmeyer,Alexandra Lorenz,Katharina Schimek,Tobias Hasenberg,Anja Patricia Ramme,Juliane Hübner,Marcus Lindner,Christopher Drewell,Sophie Bauer,Alexander Thomas,Naomia Sisoli Sambo,Frank Sonntag,Roland Lauster,Uwe Marx +13 more
TL;DR: This study is the first approach to establish a system for in vitro microfluidic ADME profiling and repeated dose systemic toxicity testing of drug candidates over 28 days in co-culture, and assures near to physiological fluid-to-tissue ratios.
Journal ArticleDOI
Gut-on-a-Chip microenvironment induces human intestinal cells to undergo villus differentiation
TL;DR: The ability of the human Gut-on-a-Chip to recapitulate the 3D structures, differentiated cell types, and multiple physiological functions of normal human intestinal villi may provide a powerful alternative in vitro model for studies on intestinal physiology and digestive diseases, as well as drug development.
Journal ArticleDOI
Engineering cellular microenvironments to improve cell-based drug testing.
TL;DR: This review explores the biological advances made by semiconductor tools to spatially organize cells and their adhesions and discusses how they could enable high-throughput cell-based assays.
References
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Journal ArticleDOI
Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings
TL;DR: Experimental and computational approaches to estimate solubility and permeability in discovery and development settings are described in this article, where the rule of 5 is used to predict poor absorption or permeability when there are more than 5 H-bond donors, 10 Hbond acceptors, and the calculated Log P (CLogP) is greater than 5 (or MlogP > 415).
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Active transport of sodium as the source of electric current in the short-circuited isolated frog skin.
Hans H. Ussing,K. Zerahn +1 more
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Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells
Per Artursson,Johan Karlsson +1 more
TL;DR: The results indicate that Caco-2 monolayers can be used as a model for studies on intestinal drug absorption and a good correlation was obtained between data on oral absorption in humans and the results in the Cco-2 model.
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Comparison of the gastrointestinal anatomy, physiology, and biochemistry of humans and commonly used laboratory animals
TL;DR: In addition to metabolic differences, the anatomical, physiological, and biochemical differences in the gastrointestinal (G.I.) tract of the human and common laboratory animals can cause significant variation in drug absorption from the oral route.
Journal ArticleDOI
Dissolution Testing as a Prognostic Tool for Oral Drug Absorption: Immediate Release Dosage Forms
TL;DR: The aims of this article are to clarify under which circumstances dissolution testing can be prognostic for in vivo performance, and to present physiological data relevant to the design of dissolution tests, particularly with respect to the composition, volume, flow rates and mixing patterns of the fluids in the gastrointestinal tract.
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