On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein

Mun, Ellina A., Morrison, Peter W. J. ORCID: https://orcid.org/0000-0002-3712-7908, Williams, Adrian C. and Khutoryanskiy, Vitaliy V. 2014. On the barrier properties of the cornea: a microscopy study of the penetration of fluorescently labeled nanoparticles, polymers, and sodium fluorescein. Molecular Pharmaceutics 11 (10) , pp. 3556-3564. 10.1021/mp500332m

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	cornea; fluorescence; PEGylated nanoparticles; permeation; silica nanoparticles; β-cyclodextrin
Publisher:	American Chemical Society
ISSN:	1543-8384
Date of First Compliant Deposit:	30 May 2017
Date of Acceptance:	22 August 2014
Last Modified:	05 May 2023 11:52
URI:	https://orca.cardiff.ac.uk/id/eprint/100968

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