Ion-activated in situ gelling systems for antisense oligodeoxynucleotide delivery to the ocular surface

Rupenthal, Ilva D., Alany, Raid G. and Green, Colin R. (2011) Ion-activated in situ gelling systems for antisense oligodeoxynucleotide delivery to the ocular surface. Molecular Pharmaceutics, 8(6), pp. 2282-2290. ISSN (print) 1543-8384

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Abstract

Ion-activated in situ gelling systems are able to cross-link with the cations present in the tear fluid, forming a gel on the ocular surface and prolonging corneal contact time. Corneal scrape wounding offers an exceptional model to investigate the efficacy of these formulations for connexin43 (Cx43) antisense oligodeoxynucleotide (AsODN) delivery used to improve wound repair. Systems based on gellan gum and carrageenan have previously been found advantageous in terms of their physicochemical properties, in vitro and in vivo release profiles and precorneal retention. The present study describes AsODN penetration into corneal tissue after wounding and determines the formulations' delivery efficacy by evaluating wound size, tissue inflammation and connexin levels. No difference was shown between the penetration patterns of the formulations, with most of the AsODN accumulating in the epithelium close to the wound leading edge and the stroma underlying the wound. However, significant differences were seen in the delivery efficacy, with gellan gum and carrageenan based systems resulting in the lowest connexin levels and subsequently in the greatest reduction in wound size, the least stromal edema and hypercellularity. This demonstrates their potential use as delivery vehicles for AsODNs to the ocular surface.

Item Type: Article
Research Area: Pharmacy
Faculty, School or Research Centre: Faculty of Science, Engineering and Computing > School of Pharmacy and Chemistry
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Depositing User: Gemma Sansom
Date Deposited: 02 Jan 2013 15:06
Last Modified: 02 Jan 2013 15:06
URI: http://eprints.kingston.ac.uk/id/eprint/24354

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