Nanofibrous scaffolds support a 3D in vitro permeability model of the human intestinal epitheleum
Patient, J.D.; Hajiali, H.; Harris, K.; Abrahamsson, B.; Tannergreen, C.; White, L.J.; Ghaemmaghami, A.M.; Williams, P.M.; Roberts, C.J.; Rose, F.R.A.J.
Professor AMIR GHAEMMAGHAMI AMIR.GHAEMMAGHAMI@NOTTINGHAM.AC.UK
Professor of Immunology and Immuno-Bioengineering
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.
|Journal Article Type||Article|
|Publication Date||May 10, 2019|
|Peer Reviewed||Peer Reviewed|
|APA6 Citation||Patient, J., Hajiali, H., Harris, K., Abrahamsson, B., Tannergreen, C., White, L., …Rose, F. (2019). Nanofibrous scaffolds support a 3D in vitro permeability model of the human intestinal epitheleum. Frontiers in Pharmacology, 10, doi:10.3389/fphar.2019.00456|
You might also like
Integrin-mediated interactions control macrophage polarization in 3D hydrogels