QobuR - A new in vitro human corneal epithelial model for preclinical drug screening

Eur J Pharm Biopharm. 2019 Mar:136:164-173. doi: 10.1016/j.ejpb.2019.01.023. Epub 2019 Jan 25.

Abstract

A new in vitro human corneal epithelial model (QobuR) obtained from normal limbal tissue has been developed to study ocular irritancy of different ophthalmic compounded drugs. Phenotypical characterization and trans-epithelial electrical resistance (TEER) of QobuR revealed essential similarities compared with a native human cornea, displaying functional markers and TEER values near 1500 Ωcm2 at day 7th of cellular differentiation. Using this model, ocular irritancy and barrier integrity alterations were evaluated using MTT reaction and variations in TEER. We found that some of the Non-Irritant products evaluated still damage the corneal epithelial integrity and current protocols for ocular irritancy should therefore include a barrier integrity evaluation. Moreover, in order to comprehensively evaluate corneal permeability of the active ingredients, we propose the use of QobuR as an all-in-one alternative method for evaluating ocular irritancy, barrier disruptions and permeability rates of topically applied ocular drugs to improve current in vitro drug testing procedures.

Keywords: Alternative method; Barrier disruptions; Drug absorption; In vitro cornea model; Ocular irritancy; QobuR; TEER measurement.

MeSH terms

  • Adult
  • Aged
  • Cells, Cultured
  • Cornea / drug effects
  • Cornea / metabolism
  • Drug Evaluation, Preclinical / methods
  • Electric Impedance*
  • Epithelium, Corneal / drug effects*
  • Epithelium, Corneal / metabolism*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Models, Biological*
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / metabolism*
  • Transendothelial and Transepithelial Migration / drug effects*
  • Transendothelial and Transepithelial Migration / physiology

Substances

  • Ophthalmic Solutions