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Targeted dermal delivery of highly potent anti-varicella zoster virus nucleoside analogues from saturated solutions and ethanolic oil-in-water creams

Jarvis, C. A., Heard, Charles Martin and McGuigan, Christopher 2003. Targeted dermal delivery of highly potent anti-varicella zoster virus nucleoside analogues from saturated solutions and ethanolic oil-in-water creams. Journal of drug targeting 11 (7) , pp. 433-441. 10.1080/1061186042000201990

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Abstract

Varicella zoster virus (VZV) is responsible for causing chickenpox and shingles infections, the latter of which can lead to long-term post-herpetic neuralgia (PHN), the most common complication of VZV infections. A class of anti-VZV nucleoside analogues has been synthesised that shows up to 30,000 times the potency of aciclovir in vitro. The relatively high lipophilicities exhibited by the compounds led them to be selected for dermal delivery. The aim was to assess the relative penetration and permeation of the compounds into and through the skin, ideally targeting the region of skin in which the reactivated virus replicates. By targeting the skin it should be possible to reduce the viral load that causes damage to the nerves, thereby limiting zoster-associated pain, in particular PHN. Three compounds, as saturated solutions or as ethanol-based creams, were applied to full-thickness pig ear skin in Franz-type diffusion cells. An ethanolic and water receptor phases were compared. Samples of the receptor phase were taken at specific intervals, followed by tape stripping and separation of the remaining membrane at the end of the experiment. Analysis of the samples showed that all three compounds penetrated into the ethanolic receptor phase to a considerable degree, while only the least lipophilic compound entered the water receptor phase. The effects of the organic solvent in the receptor phase were visible in both the penetration and permeation of the compounds. All three compounds were distributed throughout the membrane in a manner that indicates that the site of viral replication in the skin is reached.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Systems Immunity Research Institute (SIURI)
Subjects: R Medicine > RS Pharmacy and materia medica
Publisher: Taylor & Francis
ISSN: 1061-186X
Last Modified: 21 Oct 2017 06:26
URI: http://orca-mwe.cf.ac.uk/id/eprint/67494

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