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

• Published in: Sci Vol. 3; no. 3; p. 30
• Main Authors: Žiniauskaitė, Agnė, Cėpla, Vytautas, Jelinskas, Tadas, Eimont, Romuald, Ulčinas, Artūras, Aldonytė, Rūta, Valiokas, Ramūnas, Kalesnykas, Giedrius, Hakkarainen, Jenni J.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 22-06-2021
• Subjects: Bioavailability; Cell culture; Collagen; collagen hydrogel; Cornea; Drugs; Glass substrates; Hydrogels; in vitro corneal model; Membranes; Microscopy; Permeability; R&D; Research & development; Values; United States > US; Berlin Germany; Japan; Germany
• ISSN: 2413-4155; 2413-4155
• DOI: 10.3390/sci3030030

There is a growing need for novel in vitro corneal models to replace animal-based ex vivo tests in drug permeability studies. In this study, we demonstrated a corneal mimetic that models the stromal and epithelial compartments of the human cornea. Human corneal epithelial cells (HCE-T) were grown on top of a self-supporting porcine collagen-based hydrogel. Cross-sections of the multi-layers were characterized by histological staining and immunocytochemistry of zonula oc-cludens-1 protein (ZO-1) and occludin. Furthermore, water content and bssic 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. A multilayered structure of HCE-T cells and the expression of ZO-1 and occludin in the full thickness of the multilayer were observed. The hydrogel-based corneal model exhibited an excellent correlation to rabbit corneal permeability (r = 0.96), whereas the 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.