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In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection

Houston, David M. J., Robins, Bethan, Bugert, Joachim J., Denyer, Stephen P. and Heard, Charles M. 2017. In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection. European Journal of Pharmaceutical Sciences 96 , pp. 99-106. 10.1016/j.ejps.2016.08.013

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Abstract

Coadministration of pomegranate rind extract (PRE) and zinc (II) ions has recently been reported as a potential new topical treatment for Herpes simplex virus (HSV) infections. In the current work we examined the in vitro topical delivery of punicalagin (major phytochemical of PRE) and zinc from hydrogels across epithelial membranes that can become infected with HSV. Porcine epidermal, buccal and vaginal mucous membranes were excised and mounted in Franz diffusion cells and dosed with a simple hydrogel containing PRE and zinc sulphate (ZnSO4). The permeation of punicalagin and zinc were determined by HPLC and ICPMS respectively; punicalagin was also determined in the basal layers by reverse tape stripping. Receptor phases from the epidermal membrane experiment were also used to challenge HSV-1 in Vero host cells, and ex vivo porcine skin was used to probe COX-2 modulation. Punicalagin and zinc permeated each of the three test membranes, with significantly greater amounts of both delivered across the epidermal membrane. The amounts of punicalagin permeating the buccal and vaginal membranes were similar, although the amount of zinc permeating the vaginal membrane was comparatively very large – it is known that zinc interacts with vaginal mucosa. The punicalagin recovered by reverse tape stripping of the epidermal, buccal and vaginal membranes gave 0.47 ± 0.016, 0.45 ± 0.052 and 0.51 ± 0.048 nM cm− 2 respectively, and were statistically the same (p < 0.05). A 2.5 log reduction was achieved against HSV-1 using diffusion cell receptor phase, and COX-2 expression was reduced by 64% in ex vivo skin after 6 h. Overall, a hydrogel containing 1.25 mg mL− 1 PRE and 0.25 M ZnSO4 was able to topically deliver both the major bioactive compound within PRE and Zn (II) across all membranes and into the site specific region of Herpes simplex vesicular clusters, while maintaining potentiated virucidal and anti-inflammatory properties. This novel therapeutic system therefore has potential for the topical treatment of HSV infections.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Subjects: R Medicine > RS Pharmacy and materia medica
Uncontrolled Keywords: Punica granatum L.; Pomegranate rind extract; Punicalagin; Zinc; Virucidal; Anti-inflammatory; Drug delivery; Herpes simplex virus; Skin; Buccal cavity; Vagina; Reverse tape stripping
Publisher: Elsevier
ISSN: 0928-0987
Date of First Compliant Deposit: 4 October 2016
Date of Acceptance: 6 August 2016
Last Modified: 03 Jul 2019 02:05
URI: http://orca.cf.ac.uk/id/eprint/95092

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