Begum, Ghazala, Leigh, Thomas, Stanley, David, Logan, Ann and Blanch, Richard James (2021) Determining the effect of ocular chemical injuries on topical drug delivery. Drug Delivery, 28 (1). pp. 2044-2050. doi:10.1080/10717544.2021.1979124 ISSN 1521-0464.

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Abstract

Ocular chemical injuries (OCIs) commonly cause ocular damage and visual loss and treatment uses topical therapies to facilitate healing and limit complications. However, the impact of chemical injury on corneal barrier function and treatment penetration is unknown. Therefore, the aim of this study was to determine the effect of OCI on drug penetration and absorption. Porcine corneal explants were used to assess histological damage, electrical resistance, and the trans-corneal penetration/corneal adsorption of reference compounds (sodium fluorescein and rhodamine B) and dexamethasone. Corneal explants were injured with either 1 M sulfuric acid, or 1 M sodium hydroxide. Dexamethasone penetration was measured using high-performance liquid chromatography (HPLC) and that of fluorescein and rhodamine using fluorescence. Dexamethasone corneal adsorption was measured using enzyme-linked immunoabsorbant assay (ELISA). Both acid and alkaline injuries reduced trans-corneal electrical resistance. NaOH injury increased hydrophilic fluorescein penetration (NaOH 8.59 ± 1.50E–05 cm.min−1 vs. Hanks' Balanced Salt Solution (HBSS) 1.64 ± 1.01E–06 cm.min−1) with little impact on hydrophobic rhodamine B (1 M NaOH 6.55 ± 2.45E–04 cm.min−1 vs. HBSS 4.60 ± 0.972E–04 cm.min−1) and dexamethasone penetration (1 M NaOH 3.00 ± 0.853E–04 cm.min−1 vs. HBSS 2.69 ± 0.439E–04 cm.min−1). By contrast, H2SO4 decreased trans-corneal penetration of hydrophilic fluorescein (H2SO4 1.16 ± 14.2E–07 cm.min−1) and of hydrophobic dexamethasone (H2SO4 1.88 ± 0.646E–04 cm.min−1) and rhodamine B (H2SO4 4.60 ± 1.42E–05 cm.min−1). Acid and alkaline OCI differentially disrupted the corneal epithelial barrier function. Acid injury reduced penetration of hydrophobic dexamethasone and rhodamine B as well as hydrophilic fluorescein, which may translate clinically into reduced drug penetration after OCI, while alkaline injury increased fluorescein penetration, with minimal effect on dexamethasone and rhodamine B penetration.

Item Type:	Journal Article
Subjects:	Q Science > QM Human anatomy R Medicine > RE Ophthalmology R Medicine > RS Pharmacy and materia medica
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
SWORD Depositor:	Library Publications Router
Library of Congress Subject Headings (LCSH):	Ophthalmologic emergencies , Eye -- Wounds and injuries, Eye burns, Cornea , Drug delivery systems, Cornea -- Permeability
Journal or Publication Title:	Drug Delivery
Publisher:	Informa UK Limited
ISSN:	1521-0464
Official Date:	2021
Dates:	Date Event 2021 Published 1 October 2021 Available 6 September 2021 Accepted
Volume:	28
Number:	1
Page Range:	pp. 2044-2050
DOI:	10.1080/10717544.2021.1979124
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access (Creative Commons)
Date of first compliant deposit:	2 November 2021
Date of first compliant Open Access:	3 November 2021
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID UNSPECIFIED [NIHR] National Institute for Health Research http://dx.doi.org/10.13039/501100000272

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