Controlled in vitro delivery of voriconazole and diclofenac to the cornea using contact lenses for the treatment of Acanthamoeba keratitis

Morgan, Sian R., Pilia, Nicole, Hewitt, Melissa, Moses, Rachael L., Moseley, Ryan ORCID: https://orcid.org/0000-0002-2812-6735, Lewis, Philip N. ORCID: https://orcid.org/0000-0002-3353-0708, Morrison, Peter W. J. ORCID: https://orcid.org/0000-0002-3712-7908, Kelly, Steven L., Parker, Josie E., Whitaker, David ORCID: https://orcid.org/0000-0002-8271-7552, Quantock, Andrew J. ORCID: https://orcid.org/0000-0002-2484-3120 and Heard, Charles M. ORCID: https://orcid.org/0000-0001-9703-9777 2020. Controlled in vitro delivery of voriconazole and diclofenac to the cornea using contact lenses for the treatment of Acanthamoeba keratitis. International Journal of Pharmaceutics 579 , 119102. 10.1016/j.ijpharm.2020.119102

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Abstract

Acanthamoeba keratitis is caused by a protozoal infection of the cornea, with 80% of cases involving the improper use of contact lenses. The infection causes intense pain and is potentially blinding. However, early diagnosis improves treatment efficacy and the chances of healing. Despite the apparent accessibility of the cornea, patients do not always respond well to current eye drop treatments largely due to rapid dose loss due to blinking and nasolacrimal drainage. Here, the topical drug delivery of voriconazole alone and in combination with diclofenac via drug-loaded contact lenses, were investigated in vitro. The contact lenses were applied onto excised porcine eyeballs and maintained at 32°C under constant irrigation, with simulated tear fluid applied to mimic in vivo conditions. The drug delivered to the corneas was quantified by HPLC analysis. The system was further tested in terms of cytotoxicity and a scratch wound repopulation model, using corneal epithelial cells. Sustained drug delivery to the cornea was achieved and for voriconazole, the MIC against Acanthamoeba castellanii was attained alone and in combination with diclofenac. MTT and scratch wound data showed reasonable cell proliferation and wound repopulation at the drug doses used, supporting further development of the system to treat Acanthamoeba keratitis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Optometry and Vision Sciences Dentistry Pharmacy Healthcare Sciences
Publisher:	Elsevier
ISSN:	0378-5173
Date of First Compliant Deposit:	18 February 2020
Date of Acceptance:	29 January 2020
Last Modified:	06 Nov 2024 05:45
URI:	https://orca.cardiff.ac.uk/id/eprint/129778

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