Iontophoresis impact on corneal properties using an ex vivo bovine eye model

Abstract

This study addresses the challenge of low drug bioavailability in topical ocular administration by developing and validating an ex vivo bovine eye model chamber to evaluate the effects of iontophoresis on drug delivery and corneal properties. Transepithelial electrical resistance (TEER) was assessed as a predictor of corneal epithelial integrity in dissected bovine eyes. TEER measurements were correlated with methylene blue permeation, confirming a threshold of 4.2 kOhm·cm2 as an indicator of epithelial integrity. The model chamber enabled the application of drug solutions around a defined area of the cornea without leakage, facilitating the placement of electrodes and the application of constant electric currents. Applying iontophoresis at 2 mA/cm2 for 6 min significantly increased rhodamine B penetration into the cornea by nearly sixfold compared to passive diffusion (approximately 1.3 µg/cm2 vs. 0.24 µg/cm2), allowing detectable drug levels in the aqueous humor (27.9 ± 0.5 ng/mL). Morphological analyses revealed temporary changes in the cornea, including a 2.3-fold increase in surface roughness (from 44.6 nm to 105.3 nm) and mild collagen disorganization in the stroma, while Bowman’s membrane remained intact. A significant increase in corneal stiffness was noted, with a 200 % rise in the area under the stress–strain curve after iontophoresis. These findings provide insights into iontophoresis-induced changes and highlight the model’s potential for optimizing ocular drug delivery systems. Additionally, the model aligns with the 3Rs principles and could be instrumental in advancing the understanding of anterior segment diseases driven by structural and biomechanical alterations.