Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Introducing an Efficient In Vitro Cornea Mimetic Model for Testing Drug Permeability

Version 1 : Received: 5 May 2021 / Approved: 7 May 2021 / Online: 7 May 2021 (09:40:50 CEST)

A peer-reviewed article of this Preprint also exists.

Žiniauskaitė, A.; Cėpla, V.; Jelinskas, T.; Eimont, R.; Ulčinas, A.; Aldonytė, R.; Valiokas, R.; Kalesnykas, G.; Hakkarainen, J.J. Introducing an Efficient In Vitro Cornea Mimetic Model for Testing Drug Permeability. Sci 2021, 3, 30. Žiniauskaitė, A.; Cėpla, V.; Jelinskas, T.; Eimont, R.; Ulčinas, A.; Aldonytė, R.; Valiokas, R.; Kalesnykas, G.; Hakkarainen, J.J. Introducing an Efficient In Vitro Cornea Mimetic Model for Testing Drug Permeability. Sci 2021, 3, 30.

Journal reference: Sci 2021, 3, 30
DOI: 10.3390/sci3030030

Abstract

There is a growing need for novel in vitro corneal models to replace animal-based ex vivo test in drug permeability studies. In this study we demonstrate a corneal mimetic that models the stromal and epithelial compartments of human cornea. Human corneal epithelial cells (HCE-T) were grown on top of a self-supporting porcine collagen-based hydrogel. Cross sections of the multilayers were characterized by histological staining and immunocytochemistry of zonula occludens-1 protein (ZO-1) and occludin. Furthermore, water content and elastic properties of the synthetized collagen type I-based hydrogels were measured. The apparent permeability coefficient (Papp) values of a representative set of ophthalmic drugs were measured and correlated to rabbit cornea Papp values found in the literature. Multilayered structure of HCE-T cells and expression of ZO-1 and occludin in full thickness of multilayer were observed. The hydrogel-based corneal model exhibited excellent correlation to rabbit corneal permeability (r=0.96), whereas insert-grown HCE-T multilayer was more permeable and the correlation to the rabbit corneal permeability was lower (r=0.89). The hydrogel-based human corneal model predicts the rabbit corneal permeability more reliably in comparison to HCE-T cells grown in inserts. This in vitro human corneal model can be successfully employed for drug permeability tests whilst avoiding ethical issues and reducing costs.

Keywords

in vitro corneal model; collagen hydrogel; permeability

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