Investigation of iminosulfuranes as novel transdermal penetration enhancers: enhancement activity and cytotoxicity
Very few chemical enhancers for transdermal drug delivery have been approved for clinical use due to irritancy and toxicity concerns. Novel chemical enhancers (iminosulfuranes) were synthesized and studied for their activity and toxicity. Skin was treated with 0.4 M 1-5 for 1 h before hydrocortisone...
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| Veröffentlicht in: | Pharmaceutical research 2005-11, Vol.22 (11), p.1918-1925 |
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| creator | Song, Yifan Xiao, Chunhong Mendelsohn, Richard Zheng, Tao Strekowski, Lucjan Michniak, Bozena |
| description | Very few chemical enhancers for transdermal drug delivery have been approved for clinical use due to irritancy and toxicity concerns. Novel chemical enhancers (iminosulfuranes) were synthesized and studied for their activity and toxicity.
Skin was treated with 0.4 M 1-5 for 1 h before hydrocortisone was applied. Samples were taken over 24 h and analyzed by high-performance liquid chromatography. Dermal fibroblasts and epidermal keratinocytes were treated with 0-1.2 M 1-5 for 24 h and cytotoxicity assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] was performed. Furthermore, enhancement activity of 0-0.4 M 2 was studied. Partition coefficient of the model drugs into stratum corneum (SC) was measured and confocal Raman microscopy was used to study the penetration process and possible mechanisms of action of the enhancers. Quantitative structure-activity relationship (QSAR) was analyzed to study the contribution of different intramolecular descriptors to enhancement activity.
Iminosulfurane 2 showed the highest enhancement activity. All compounds below 0.2 M were safe to skin cells, and 2 was effective at the concentration of 0.1 and 0.2 M. Mechanisms of action of 2 may include increasing partition coefficient of the model drug into SC and interaction between the enhancer and lipids and protein in the SC. QSAR study indicated contribution of several factors to activity: partition coefficient, hydrogen-bond acceptor, and optimal molecular size.
Enhancement activity of 2 was achieved without any cytotoxicity. |
| doi_str_mv | 10.1007/s11095-005-7416-4 |
| format | Article |
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Skin was treated with 0.4 M 1-5 for 1 h before hydrocortisone was applied. Samples were taken over 24 h and analyzed by high-performance liquid chromatography. Dermal fibroblasts and epidermal keratinocytes were treated with 0-1.2 M 1-5 for 24 h and cytotoxicity assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] was performed. Furthermore, enhancement activity of 0-0.4 M 2 was studied. Partition coefficient of the model drugs into stratum corneum (SC) was measured and confocal Raman microscopy was used to study the penetration process and possible mechanisms of action of the enhancers. Quantitative structure-activity relationship (QSAR) was analyzed to study the contribution of different intramolecular descriptors to enhancement activity.
Iminosulfurane 2 showed the highest enhancement activity. All compounds below 0.2 M were safe to skin cells, and 2 was effective at the concentration of 0.1 and 0.2 M. Mechanisms of action of 2 may include increasing partition coefficient of the model drug into SC and interaction between the enhancer and lipids and protein in the SC. QSAR study indicated contribution of several factors to activity: partition coefficient, hydrogen-bond acceptor, and optimal molecular size.
Enhancement activity of 2 was achieved without any cytotoxicity.</description><identifier>ISSN: 0724-8741</identifier><identifier>EISSN: 1573-904X</identifier><identifier>DOI: 10.1007/s11095-005-7416-4</identifier><identifier>PMID: 16132348</identifier><language>eng</language><publisher>United States: Springer Nature B.V</publisher><subject>Administration, Cutaneous ; Animals ; Chromatography ; Cytotoxicity ; Dimethyl Sulfoxide ; Drug Delivery Systems ; Epidermis - metabolism ; Hydrocortisone - administration & dosage ; Hydrocortisone - pharmacokinetics ; Investigations ; Lipids ; Male ; Mice ; Mice, Hairless ; Quantitative Structure-Activity Relationship ; Skin - drug effects ; Skin - metabolism ; Skin - pathology ; Skin Absorption - drug effects ; Sulfones ; Sulfur Compounds - pharmacology ; Toxicity ; Transdermal medication</subject><ispartof>Pharmaceutical research, 2005-11, Vol.22 (11), p.1918-1925</ispartof><rights>Springer Science + Business Media, Inc. 2005</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c423t-333ce6e1791b8cc41d597600f23d4869a80284fd82f617bee57be6ca693f4b573</citedby><cites>FETCH-LOGICAL-c423t-333ce6e1791b8cc41d597600f23d4869a80284fd82f617bee57be6ca693f4b573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16132348$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Song, Yifan</creatorcontrib><creatorcontrib>Xiao, Chunhong</creatorcontrib><creatorcontrib>Mendelsohn, Richard</creatorcontrib><creatorcontrib>Zheng, Tao</creatorcontrib><creatorcontrib>Strekowski, Lucjan</creatorcontrib><creatorcontrib>Michniak, Bozena</creatorcontrib><title>Investigation of iminosulfuranes as novel transdermal penetration enhancers: enhancement activity and cytotoxicity</title><title>Pharmaceutical research</title><addtitle>Pharm Res</addtitle><description>Very few chemical enhancers for transdermal drug delivery have been approved for clinical use due to irritancy and toxicity concerns. Novel chemical enhancers (iminosulfuranes) were synthesized and studied for their activity and toxicity.
Skin was treated with 0.4 M 1-5 for 1 h before hydrocortisone was applied. Samples were taken over 24 h and analyzed by high-performance liquid chromatography. Dermal fibroblasts and epidermal keratinocytes were treated with 0-1.2 M 1-5 for 24 h and cytotoxicity assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] was performed. Furthermore, enhancement activity of 0-0.4 M 2 was studied. Partition coefficient of the model drugs into stratum corneum (SC) was measured and confocal Raman microscopy was used to study the penetration process and possible mechanisms of action of the enhancers. Quantitative structure-activity relationship (QSAR) was analyzed to study the contribution of different intramolecular descriptors to enhancement activity.
Iminosulfurane 2 showed the highest enhancement activity. All compounds below 0.2 M were safe to skin cells, and 2 was effective at the concentration of 0.1 and 0.2 M. Mechanisms of action of 2 may include increasing partition coefficient of the model drug into SC and interaction between the enhancer and lipids and protein in the SC. QSAR study indicated contribution of several factors to activity: partition coefficient, hydrogen-bond acceptor, and optimal molecular size.
Enhancement activity of 2 was achieved without any cytotoxicity.</description><subject>Administration, Cutaneous</subject><subject>Animals</subject><subject>Chromatography</subject><subject>Cytotoxicity</subject><subject>Dimethyl Sulfoxide</subject><subject>Drug Delivery Systems</subject><subject>Epidermis - metabolism</subject><subject>Hydrocortisone - administration & dosage</subject><subject>Hydrocortisone - pharmacokinetics</subject><subject>Investigations</subject><subject>Lipids</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Hairless</subject><subject>Quantitative Structure-Activity Relationship</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Skin Absorption - drug effects</subject><subject>Sulfones</subject><subject>Sulfur Compounds - pharmacology</subject><subject>Toxicity</subject><subject>Transdermal medication</subject><issn>0724-8741</issn><issn>1573-904X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNpdUU1rGzEQFaWhdtz-gF6C6KG3TfS1Wm1uxbSJwZBLAr0JWTvbyuxKjqQ19b-PHDsUcpkPzXsPzTyEvlJyTQlpbhKlpK0rQuqqEVRW4gOa07rhVUvE749oThomKlVGM3SZ0pYQomgrPqEZlZQzLtQcxZXfQ8ruj8kueBx67EbnQ5qGforGQ8ImYR_2MOBc-tRBHM2Ad-Ch9K8c8H-NtxDT7Vs5gs_Y2Oz2Lh-w8R22hxxy-OdsefiMLnozJPhyzgv09Ovn4_K-Wj_crZY_1pUVjOeKc25BAm1aulHWCtrVbSMJ6RnvhJKtUYQp0XeK9ZI2G4C6BGmNbHkvNuUKC_T9pLuL4XkqS-rRJQvDUNYKU9KMMCYVrwvw2zvgNkzRl79pdoS0kh3V6AlkY0gpQq930Y0mHjQl-uiGPrmhixv66IYWhXN1Fp42I3T_Gefz8xe8kofM</recordid><startdate>20051101</startdate><enddate>20051101</enddate><creator>Song, Yifan</creator><creator>Xiao, Chunhong</creator><creator>Mendelsohn, Richard</creator><creator>Zheng, Tao</creator><creator>Strekowski, Lucjan</creator><creator>Michniak, Bozena</creator><general>Springer Nature 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>3V.</scope><scope>7RV</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20051101</creationdate><title>Investigation of iminosulfuranes as novel transdermal penetration enhancers: enhancement activity and cytotoxicity</title><author>Song, Yifan ; Xiao, Chunhong ; Mendelsohn, Richard ; Zheng, Tao ; Strekowski, Lucjan ; Michniak, Bozena</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c423t-333ce6e1791b8cc41d597600f23d4869a80284fd82f617bee57be6ca693f4b573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Administration, Cutaneous</topic><topic>Animals</topic><topic>Chromatography</topic><topic>Cytotoxicity</topic><topic>Dimethyl Sulfoxide</topic><topic>Drug Delivery Systems</topic><topic>Epidermis - metabolism</topic><topic>Hydrocortisone - administration & dosage</topic><topic>Hydrocortisone - pharmacokinetics</topic><topic>Investigations</topic><topic>Lipids</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Hairless</topic><topic>Quantitative Structure-Activity Relationship</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Skin Absorption - drug effects</topic><topic>Sulfones</topic><topic>Sulfur Compounds - pharmacology</topic><topic>Toxicity</topic><topic>Transdermal medication</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Song, Yifan</creatorcontrib><creatorcontrib>Xiao, Chunhong</creatorcontrib><creatorcontrib>Mendelsohn, Richard</creatorcontrib><creatorcontrib>Zheng, Tao</creatorcontrib><creatorcontrib>Strekowski, Lucjan</creatorcontrib><creatorcontrib>Michniak, Bozena</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Neurosciences Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Pharmaceutical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Song, Yifan</au><au>Xiao, Chunhong</au><au>Mendelsohn, Richard</au><au>Zheng, Tao</au><au>Strekowski, Lucjan</au><au>Michniak, Bozena</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Investigation of iminosulfuranes as novel transdermal penetration enhancers: enhancement activity and cytotoxicity</atitle><jtitle>Pharmaceutical research</jtitle><addtitle>Pharm Res</addtitle><date>2005-11-01</date><risdate>2005</risdate><volume>22</volume><issue>11</issue><spage>1918</spage><epage>1925</epage><pages>1918-1925</pages><issn>0724-8741</issn><eissn>1573-904X</eissn><abstract>Very few chemical enhancers for transdermal drug delivery have been approved for clinical use due to irritancy and toxicity concerns. Novel chemical enhancers (iminosulfuranes) were synthesized and studied for their activity and toxicity.
Skin was treated with 0.4 M 1-5 for 1 h before hydrocortisone was applied. Samples were taken over 24 h and analyzed by high-performance liquid chromatography. Dermal fibroblasts and epidermal keratinocytes were treated with 0-1.2 M 1-5 for 24 h and cytotoxicity assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] was performed. Furthermore, enhancement activity of 0-0.4 M 2 was studied. Partition coefficient of the model drugs into stratum corneum (SC) was measured and confocal Raman microscopy was used to study the penetration process and possible mechanisms of action of the enhancers. Quantitative structure-activity relationship (QSAR) was analyzed to study the contribution of different intramolecular descriptors to enhancement activity.
Iminosulfurane 2 showed the highest enhancement activity. All compounds below 0.2 M were safe to skin cells, and 2 was effective at the concentration of 0.1 and 0.2 M. Mechanisms of action of 2 may include increasing partition coefficient of the model drug into SC and interaction between the enhancer and lipids and protein in the SC. QSAR study indicated contribution of several factors to activity: partition coefficient, hydrogen-bond acceptor, and optimal molecular size.
Enhancement activity of 2 was achieved without any cytotoxicity.</abstract><cop>United States</cop><pub>Springer Nature B.V</pub><pmid>16132348</pmid><doi>10.1007/s11095-005-7416-4</doi><tpages>8</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0724-8741 |
| ispartof | Pharmaceutical research, 2005-11, Vol.22 (11), p.1918-1925 |
| issn | 0724-8741 1573-904X |
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| source | MEDLINE; SpringerNature Journals |
| subjects | Administration, Cutaneous Animals Chromatography Cytotoxicity Dimethyl Sulfoxide Drug Delivery Systems Epidermis - metabolism Hydrocortisone - administration & dosage Hydrocortisone - pharmacokinetics Investigations Lipids Male Mice Mice, Hairless Quantitative Structure-Activity Relationship Skin - drug effects Skin - metabolism Skin - pathology Skin Absorption - drug effects Sulfones Sulfur Compounds - pharmacology Toxicity Transdermal medication |
| title | Investigation of iminosulfuranes as novel transdermal penetration enhancers: enhancement activity and cytotoxicity |
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