Sci (Jun 2021)

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

  • Agnė Žiniauskaitė,
  • Vytautas Cėpla,
  • Tadas Jelinskas,
  • Romuald Eimont,
  • Artūras Ulčinas,
  • Rūta Aldonytė,
  • Ramūnas Valiokas,
  • Giedrius Kalesnykas,
  • Jenni J. Hakkarainen

DOI
https://doi.org/10.3390/sci3030030
Journal volume & issue
Vol. 3, no. 3
p. 30

Abstract

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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.

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