On the Barrier Properties of the Cornea: A Microscopy Study of the Penetration of Fluorescently Labeled Nanoparticles, Polymers, and Sodium Fluorescein

Abstract

Overcoming the natural defensive barrier functions of the eye remains one of the greatest challenges of ocular drug delivery. Cornea is a chemical and mechanical barrier preventing the passage of any foreign bodies including drugs into the eye, but the factors limiting penetration of permeants and nanoparticulate drug delivery systems through the cornea are still not fully understood. In this study, we investigate these barrier properties of the cornea using thiolated and PEGylated (750 and 5000 Da) nanoparticles, sodium fluorescein, and two linear polymers (dextran and polyethylene glycol). Experiments used intact bovine cornea in addition to bovine cornea de-epithelialized or tissues pretreated with cyclodextrin. It was shown that corneal epithelium is the major barrier for permeation; pretreatment of the cornea with β-cyclodextrin provides higher permeation of low molecular weight compounds, such as sodium fluorescein, but does not enhance penetration of nanoparticles and larger molecules. Studying penetration of thiolated and PEGylated (750 and 5000 Da) nanoparticles into the de-epithelialized ocular tissue revealed that interactions between corneal surface and thiol groups of nanoparticles were more significant determinants of penetration than particle size (for the sizes used here). PEGylation with polyethylene glycol of a higher molecular weight (5000 Da) allows penetration of nanoparticles into the stroma, which proceeds gradually, after an initial 1 h lag phase.

Evaluation of 2 ex vivo Bovine Cornea Storage Protocols for Drug Delivery Applications

“…Sodium fluorescein was used as a model dye due to its moderate but easily quantifiable permeability through intact corneal tissue [6, 18]. Hence, a loss in tissue integrity would be readily identifiable with this dye.…”

Delivery of therapeutics for deep-seated ocular conditions – status quo

“…Of these layers, the epithelium is the major barrier for transcorneal permeation, especially for nanoparticles and larger molecular weight drugs. [19] For example, it has been found that, of the five layers of the cornea, the corneal epithelium is the rate-limiting barrier for most transcorneal permeation, especially water-soluble compounds, whereas the corneal stroma and endothelium are only a significant barrier for small, lipophilic compounds. [20,21] This is due specifically to the suprabasal layer of the cornea that contains tight junctions between cells as well as a high clauden density limiting the passage of even small molecules into the ocular region.…”

“…[15][16][17] Corneal epithelium barrier -The epithelial layer of the cornea is the rate-limiting barrier for most transcorneal penetration. [19][20][21] -Due to the narrow intercellular tight junctions and high claudin density in the superficial layer of the corneal epithelium. [22] Vitreous clearance of drug -Once drugs penetrate into the vitreous body, they can be cleared via two routes: an anterior route and a posterior route.…”

Experimental purulent corneal ulcer in rabbits as a model to study ocular dosage forms

“…Роговица подвержена повышенной опасно-сти, потому что выступает в роли защитно-го барьера для внутренних структур глаза. Она препятствует проникновению не толь-ко инородных тел, но и лекарственных пре-паратов [3,4].…”