New Human Organotypic Corneal Tissue Model for Ophthalmic Drug Delivery Studies

Investigative Ophthalmology & Visual Science
Yulia KaluzhnyMitchell Klausner

Abstract

The purpose of the current work was to develop a physiologically relevant, in vitro human three-dimensional (3D) corneal epithelial tissue model for use in ophthalmic drug development. Normal human corneal epithelial cells were cultured at the air-liquid interface to produce the 3D corneal tissue model. Corneal barrier was determined by measuring transepithelial electrical resistance (TEER). Quantitative PCR arrays were utilized to investigate expression of 84 phase I/II metabolizing enzymes and 84 drug transporter genes. Permeability was evaluated using model compounds with a wide range of hydrophobicity, molecular weight, and excipients. Finally, different formulations of latanoprost and bimatoprost were administered and drug absorption and tissue viability and integrity were investigated. Histologic assessment and TEER of the corneal tissue model revealed tissue structure, thickness, and barrier formation (1000 ± 146 Ω·cm2) comparable to native human corneal epithelium. The 3D corneal tissue expressed tight junctions, mucins, and key corneal epithelial detoxification enzymes. Drug-metabolizing enzyme and transporter gene expression in 3D corneal tissue and excised human corneal epithelium were highly correlated (r2 = 0.87). ...Continue Reading

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Citations

Mar 24, 2020·Lab on a Chip·Rodi Abdalkader, Ken-Ichiro Kamei
Apr 3, 2020·Biological & Pharmaceutical Bulletin·Ryosuke Fukuda, Tatsuya Murakami
Jul 22, 2019·Pharmaceutics·Roman V MoiseevVitaliy V Khutoryanskiy
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Sep 6, 2020·Experimental Eye Research·Thomas Michael ShijuSteven E Wilson
Feb 6, 2021·In Vitro Cellular & Developmental Biology. Animal·Yulia Kaluzhny, Mitchell Klausner
Dec 19, 2020·Pharmaceutics·Laura García-Posadas, Yolanda Diebold
Oct 2, 2021·Drug Delivery·Ghazala BegumRichard James Blanch

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