Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed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

How to cite: 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. Preprints 2021, 2021050133 (doi: 10.20944/preprints202105.0133.v1). 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. Preprints 2021, 2021050133 (doi: 10.20944/preprints202105.0133.v1).

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.

Subject Areas

in vitro corneal model; collagen hydrogel; permeability

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