In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection
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 hyd...
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| Veröffentlicht in: | European journal of pharmaceutical sciences 2017-01, Vol.96, p.99-106 |
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| creator | Houston, David M.J. Robins, Bethan Bugert, Joachim J. Denyer, Stephen P. Heard, Charles M. |
| description | 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 |
| doi_str_mv | 10.1016/j.ejps.2016.08.013 |
| format | Article |
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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<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 6h.
Overall, a hydrogel containing 1.25mgmL−1 PRE and 0.25M 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.
[Display omitted]</description><identifier>ISSN: 0928-0987</identifier><identifier>EISSN: 1879-0720</identifier><identifier>DOI: 10.1016/j.ejps.2016.08.013</identifier><identifier>PMID: 27516148</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject><![CDATA[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]]></subject><ispartof>European journal of pharmaceutical sciences, 2017-01, Vol.96, p.99-106</ispartof><rights>2016 Elsevier B.V.</rights><rights>Copyright © 2016 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c400t-43b9aa93172eb460231b7df0e0c915f71a51a3894d5f5e31a20a6dcecc11341d3</citedby><cites>FETCH-LOGICAL-c400t-43b9aa93172eb460231b7df0e0c915f71a51a3894d5f5e31a20a6dcecc11341d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejps.2016.08.013$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27516148$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Houston, David M.J.</creatorcontrib><creatorcontrib>Robins, Bethan</creatorcontrib><creatorcontrib>Bugert, Joachim J.</creatorcontrib><creatorcontrib>Denyer, Stephen P.</creatorcontrib><creatorcontrib>Heard, Charles M.</creatorcontrib><title>In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection</title><title>European journal of pharmaceutical sciences</title><addtitle>Eur J Pharm Sci</addtitle><description>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<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 6h.
Overall, a hydrogel containing 1.25mgmL−1 PRE and 0.25M 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.
[Display omitted]</description><subject>Animals</subject><subject>Anti-inflammatory</subject><subject>Anti-Inflammatory Agents - administration & dosage</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Antiviral Agents - administration & dosage</subject><subject>Antiviral Agents - pharmacology</subject><subject>Buccal cavity</subject><subject>Cercopithecus aethiops</subject><subject>Cyclooxygenase 2 - metabolism</subject><subject>Drug delivery</subject><subject>Female</subject><subject>Herpes Simplex</subject><subject>Herpes simplex virus</subject><subject>Herpesvirus 1, Human - drug effects</subject><subject>Herpesvirus 1, Human - growth & development</subject><subject>Hydrogels - administration & dosage</subject><subject>Hydrogels - pharmacology</subject><subject>Hydrolyzable Tannins - administration & dosage</subject><subject>Hydrolyzable Tannins - pharmacology</subject><subject>Hypromellose Derivatives</subject><subject>In Vitro Techniques</subject><subject>Mucous Membrane - drug effects</subject><subject>Mucous Membrane - metabolism</subject><subject>Mucous Membrane - virology</subject><subject>Pomegranate rind extract</subject><subject>Punica granatum L</subject><subject>Punicalagin</subject><subject>Reverse tape stripping</subject><subject>Skin</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - virology</subject><subject>Swine</subject><subject>Vagina</subject><subject>Vero Cells</subject><subject>Virucidal</subject><subject>Zinc</subject><subject>Zinc Sulfate - administration & dosage</subject><subject>Zinc Sulfate - pharmacology</subject><issn>0928-0987</issn><issn>1879-0720</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctu1TAQhi1ERQ-FF2CBvCyLhJk4F0digyqgR6rEpqwtx5lUPiR2sJOq7VvwxjicU5asbI-_-efyM_YOIUfA-uMhp8Mc8yLdc5A5oHjBdiibNoOmgJdsB20hM2hlc85ex3gAgFo28IqdF02FNZZyx37vHb-3S_B8pjCRXqx3XLued9aP_s4aPXJtFpuYR-4HPq9ui-k7e8SerDP8cr__kKjgY-Tx5-lnWo1fI59o6oJ2FPkcvCO-eH5NYU7vaKd5pIdUPiTOuoHMVv0NOxv0GOnt6bxgP75-ub26zm6-f9tffb7JTAmwZKXoWq1bgU1BXVlDIbBr-gEITIvV0KCuUAvZln01VCRQF6Dr3pAxiKLEXlywy6Nu6uvXSnFRk42GxjE1mxpXKEUlpCyFTGhxRP-OGGhQc7CTDo8KQW1WqIParFCbFQqkSlakpPcn_bWbqP-X8rz7BHw6ApSmvLcUVDSWnKHehrQK1Xv7P_0_zdOczA</recordid><startdate>20170101</startdate><enddate>20170101</enddate><creator>Houston, David M.J.</creator><creator>Robins, Bethan</creator><creator>Bugert, Joachim J.</creator><creator>Denyer, Stephen P.</creator><creator>Heard, Charles M.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20170101</creationdate><title>In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection</title><author>Houston, David M.J. ; Robins, Bethan ; Bugert, Joachim J. ; Denyer, Stephen P. ; Heard, Charles M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c400t-43b9aa93172eb460231b7df0e0c915f71a51a3894d5f5e31a20a6dcecc11341d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Anti-inflammatory</topic><topic>Anti-Inflammatory Agents - administration & dosage</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Antiviral Agents - administration & dosage</topic><topic>Antiviral Agents - pharmacology</topic><topic>Buccal cavity</topic><topic>Cercopithecus aethiops</topic><topic>Cyclooxygenase 2 - metabolism</topic><topic>Drug delivery</topic><topic>Female</topic><topic>Herpes Simplex</topic><topic>Herpes simplex virus</topic><topic>Herpesvirus 1, Human - drug effects</topic><topic>Herpesvirus 1, Human - growth & development</topic><topic>Hydrogels - administration & dosage</topic><topic>Hydrogels - pharmacology</topic><topic>Hydrolyzable Tannins - administration & dosage</topic><topic>Hydrolyzable Tannins - pharmacology</topic><topic>Hypromellose Derivatives</topic><topic>In Vitro Techniques</topic><topic>Mucous Membrane - drug effects</topic><topic>Mucous Membrane - metabolism</topic><topic>Mucous Membrane - virology</topic><topic>Pomegranate rind extract</topic><topic>Punica granatum L</topic><topic>Punicalagin</topic><topic>Reverse tape stripping</topic><topic>Skin</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - virology</topic><topic>Swine</topic><topic>Vagina</topic><topic>Vero Cells</topic><topic>Virucidal</topic><topic>Zinc</topic><topic>Zinc Sulfate - administration & dosage</topic><topic>Zinc Sulfate - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Houston, David M.J.</creatorcontrib><creatorcontrib>Robins, Bethan</creatorcontrib><creatorcontrib>Bugert, Joachim J.</creatorcontrib><creatorcontrib>Denyer, Stephen P.</creatorcontrib><creatorcontrib>Heard, Charles M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>European journal of pharmaceutical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Houston, David M.J.</au><au>Robins, Bethan</au><au>Bugert, Joachim J.</au><au>Denyer, Stephen P.</au><au>Heard, Charles M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection</atitle><jtitle>European journal of pharmaceutical sciences</jtitle><addtitle>Eur J Pharm Sci</addtitle><date>2017-01-01</date><risdate>2017</risdate><volume>96</volume><spage>99</spage><epage>106</epage><pages>99-106</pages><issn>0928-0987</issn><eissn>1879-0720</eissn><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±0.048nMcm−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 6h.
Overall, a hydrogel containing 1.25mgmL−1 PRE and 0.25M 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.
[Display omitted]</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>27516148</pmid><doi>10.1016/j.ejps.2016.08.013</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| 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 |
| title | In vitro permeation and biological activity of punicalagin and zinc (II) across skin and mucous membranes prone to Herpes simplex virus infection |
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