Human Primary Cell-Based Organotypic Microtissues for Modeling Small Intestinal Drug Absorption

Pharmaceutical Research
Seyoum AyehunieMitchell Klausner

Abstract

The study evaluates the use of new in vitro primary human cell-based organotypic small intestinal (SMI) microtissues for predicting intestinal drug absorption and drug-drug interaction. The SMI microtissues were reconstructed using human intestinal fibroblasts and enterocytes cultured on a permeable support. To evaluate the suitability of the intestinal microtissues to model drug absorption, the permeability coefficients across the microtissues were determined for a panel of 11 benchmark drugs with known human absorption and Caco-2 permeability data. Drug-drug interactions were examined using efflux transporter substrates and inhibitors. The 3D-intestinal microtissues recapitulate the structural features and physiological barrier properties of the human small intestine. The microtissues also expressed drug transporters and metabolizing enzymes found on the intestinal wall. Functionally, the SMI microtissues were able to discriminate between low and high permeability drugs and correlated better with human absorption data (r2 = 0.91) compared to Caco-2 cells (r2 = 0.71). Finally, the functionality of efflux transporters was confirmed using efflux substrates and inhibitors which resulted in efflux ratios of >2.0 fold and by a decr...Continue Reading

References

Dec 1, 1989·Gut·R Holmes, R W Lobley
Jul 2, 2004·Therapeutic Drug Monitoring·Uwe Christians
Apr 6, 2006·The AAPS Journal·Praveen V BalimaneSaeho Chong
Aug 23, 2006·Cell·Adam J EnglerDennis E Discher
Mar 20, 2008·Nature Clinical Practice. Oncology·Yohann LoriotJean-Charles Soria
Mar 13, 2009·AAPS PharmSciTech·Erina Pretorius, Patrick J D Bouic
Jul 2, 2009·Pharmaceutical Research·Sarah Shugarts, Leslie Z Benet
Sep 26, 2009·The Journal of Pharmacology and Experimental Therapeutics·Yoshiyuki ShirasakaIkumi Tamai
Aug 26, 2010·Molecular Pharmaceutics·Noha M ZakiChristel A S Bergström
Nov 22, 2011·Future Medicinal Chemistry·Donna A Volpe
Jul 17, 2012·Journal of Cell Science·Brendon M Baker, Christopher S Chen
Mar 7, 2014·The Journal of Pharmacology and Experimental Therapeutics·Elisabeth M Hersman, Namandjé N Bumpus
Jul 1, 2005·Drug Discovery Today. Technologies·Albert P Li
Nov 26, 2014·The Journal of Cell Biology·Scott W CrawleyMatthew J Tyska
Jan 15, 2015·Journal of Laboratory Automation·Balaji SrinivasanJames J Hickman
Mar 10, 2015·Scientific Reports·Anurag MathurKevin E Healy
Apr 11, 2015·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Ilka MaschmeyerEva-Maria Materne
Apr 19, 2016·Best Practice & Research. Clinical Gastroenterology·Pawel R Kiela, Fayez K Ghishan
Sep 13, 2016·Advanced Materials·Aaron C AnselmoAna Jaklenec
Jan 31, 2017·Pharmacology & Therapeutics·Daniel F CarrMunir Pirmohamed
Nov 25, 2015·Cellular and Molecular Gastroenterology and Hepatology·Matthew J Tyska
May 24, 2017·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·A D EatonB P Hurley
Jun 10, 2017·Gut Microbes·Ana Maldonado-ContrerasBeth A McCormick

❮ Previous
Next ❯

Citations

Jul 20, 2018·Investigative Ophthalmology & Visual Science·Yulia KaluzhnyMitchell Klausner
Aug 8, 2018·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·Clément ChaletPatrick Augustijns
Oct 27, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Matthew F PetersSeyoum Ayehunie
Aug 22, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Aarti Sawant-BasakNikolaos Tsamandouras
Mar 11, 2020·Expert Opinion on Drug Discovery·Donna A Volpe
Mar 30, 2020·Scientific Reports·Chandradhish GhoshJayanta Haldar
Aug 28, 2020·Frontiers in Bioengineering and Biotechnology·Christian SchmidtJoachim Wiest
Nov 26, 2020·In Vitro Cellular & Developmental Biology. Animal·Jan MarkusSeyoum Ayehunie
Nov 26, 2020·In Vitro Cellular & Developmental Biology. Animal·Patrick J Hayden, John W Harbell
Feb 4, 2021·Drug Delivery and Translational Research·Valentina AndrettoGiovanna Lollo
Feb 4, 2021·Pharmaceutics·Glenn LemmensPatrick Augustijns
May 26, 2021·Journal of Controlled Release : Official Journal of the Controlled Release Society·Arianna FediSilvia Scaglione
Aug 31, 2021·RSC Chemical Biology·Jannik Bruun LarsenThomas Lars Andresen
Nov 20, 2021·Frontiers in Cell and Developmental Biology·Feiling SongYanhua Li
Dec 4, 2021·Nature Communications·Ozren StojanovićMirko Trajkovski

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
transmission
scanning electron microscopy
PCR

Software Mentioned

MassHunter
BioRad CFX Manager

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.