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

• Published in: European journal of pharmaceutical sciences 2017-01, Vol.96, p.99-106
• Main Authors: Houston, David M.J., Robins, Bethan, Bugert, Joachim J., Denyer, Stephen P., Heard, Charles M.
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents - administration & dosage; Anti-Inflammatory Agents - pharmacology; Antiviral Agents - administration & dosage; Antiviral Agents - pharmacology; Buccal cavity; Cercopithecus aethiops; Cyclooxygenase 2 - metabolism; Drug delivery; Female; Herpes Simplex; Herpes simplex virus; Herpesvirus 1, Human - drug effects; Herpesvirus 1, Human - growth & development; Hydrogels - administration & dosage; Hydrogels - pharmacology; Hydrolyzable Tannins - administration & dosage; Hydrolyzable Tannins - pharmacology; Hypromellose Derivatives; In Vitro Techniques; Mucous Membrane - drug effects; Mucous Membrane - metabolism; Mucous Membrane - virology; Pomegranate rind extract; Punica granatum L; Punicalagin; Reverse tape stripping; Skin; Skin - drug effects; Skin - metabolism; Skin - virology; Swine; Vagina; Vero Cells; Virucidal; Zinc; Zinc Sulfate - administration & dosage; Zinc Sulfate - pharmacology
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2016.08.013

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±0.048nMcm−2 respectively, and were statistically the same (p