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Nanofibrous scaffolds support a 3D in vitro permeability model of the human intestinal epitheleum

Patient, Jamie D.; Hajiali, Hadi; Harris, Kate; Abrahamsson, Bertil; Tannergreen, Christopher ; White, Lisa J.; Ghaemmaghami, Amir M.; Williams, Philip M.; Roberts, Clive J.; Rose, Felicity R.A.J.

Nanofibrous scaffolds support a 3D in vitro permeability model of the human intestinal epitheleum Thumbnail


Authors

Jamie D. Patient

Hadi Hajiali

Kate Harris

Bertil Abrahamsson

Christopher Tannergreen

PHIL WILLIAMS PHIL.WILLIAMS@NOTTINGHAM.AC.UK
Professor of Biophysics

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FELICITY ROSE FELICITY.ROSE@NOTTINGHAM.AC.UK
Professor of Biomaterials and Tissue Engineering



Abstract

Advances in drug research not only depend on high throughput screening to evaluate large numbers of lead compounds but also on the development of in vitro models which can simulate human tissues in terms of drug permeability and functions. Potential failures, such as poor permeability or interaction with efflux drug transporters, can be identified in epithelial Caco-2 monolayer models and can impact a drug candidate’s progression onto the next stages of the drug development process. Whilst monolayer models demonstrate reasonably good prediction of in vivo permeability for some compounds, more developed in vitro tools are needed to assess new entities that enable closer in vivo in vitro correlation. In this study, an in vitro model of the human intestinal epithelium was developed by utilizing nanofibers, fabricated using electrospinning, to mimic the structure of the basement membrane. We assessed Caco-2 cell response to these materials and investigated the physiological properties of these cells cultured on the fibrous supports, focusing on barrier integrity and drug-permeability properties. The obtained data illustrate that 2D Caco-2 Transwell® cultures exhibit artificially high trans-epithelial electrical resistance (TEER) compared to cells cultured on the 3D nanofibrous scaffolds which show TEER values similar to ex vivo porcine tissue (also measured in this study). Furthermore, our results demonstrate that the 3D nanofibrous scaffolds influence the barrier integrity of the Caco-2 monolayer to confer drug-absorption properties that more closely mimic native gut tissue particularly for studying passive epithelial transport. We propose that this 3D model is a suitable in vitro model for investigating drug absorption and intestinal metabolism.

Citation

Patient, J. D., Hajiali, H., Harris, K., Abrahamsson, B., Tannergreen, C., White, L. J., …Rose, F. R. (2019). Nanofibrous scaffolds support a 3D in vitro permeability model of the human intestinal epitheleum. Frontiers in Pharmacology, 10, Article 456. https://doi.org/10.3389/fphar.2019.00456

Journal Article Type Article
Acceptance Date Apr 11, 2019
Online Publication Date May 10, 2019
Publication Date May 10, 2019
Deposit Date Apr 17, 2019
Publicly Available Date Apr 17, 2019
Journal Frontiers in Pharmacology
Electronic ISSN 1663-9812
Publisher Frontiers Media
Peer Reviewed Peer Reviewed
Volume 10
Article Number 456
DOI https://doi.org/10.3389/fphar.2019.00456
Public URL https://nottingham-repository.worktribe.com/output/1818815
Publisher URL https://www.frontiersin.org/articles/10.3389/fphar.2019.00456/full