{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:26:54Z","timestamp":1790915214186,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2005,5,16]],"date-time":"2005-05-16T00:00:00Z","timestamp":1116201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Gene Medicine"],"published-print":{"date-parts":[[2005,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Localized scleroderma (morphea and linear scleroderma) is a connective tissue disease, accompanied by excessive proliferation and deposition of collagen within the skin, inflammation, vasculopathy and a deranged immune system. Interferon \u03b3 (IFN\u03b3), an inhibitor of collagen synthesis and an immunomodulator, could be a potential therapeutic agent if it could be delivered into or expressed locally in affected skin in a non\u2010invasive manner. In this study, the feasibility of topical delivery of the\n                      <jats:italic>IFN<\/jats:italic>\n                      \u03b3 gene and expression of IFN\u03b3 were investigated in mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Novel dicationic (gemini) surfactant (spacer length n = 2\u201316; alkyl chain m = 12 or 16)\u2013DNA complexes were formulated and characterized by circular dichroism and atomic force microscopy to select gemini analogues with the highest transfection efficiency (TE). Transfection and cellular expression of\n                      <jats:italic>IFN<\/jats:italic>\n                      \u03b3 from the bicistronic pGTmCMV.IFN\u2010GFP plasmid were evaluated in PAM 212 keratinocyte culture by ELISA and fluorescence microscopy. Topical delivery of plasmid using liposomal and nanoemulsion systems, based on gemini surfactant 16\u20103\u201016, was evaluated in mice by IFN\u03b3 expression analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>In vitro<\/jats:italic>\n                      TE was found to be dependent on the spacer length of the gemini surfactant, with the C3 spacer showing the highest activity (both 12\u20103\u201012 and 16\u20103\u201016). Both gemini cationic liposomes and gemini nanoemulsion (3 \u00d7 25 \u00b5g DNA\/animal) produced significantly higher levels of IFN\u03b3 in the skin (359.4 and 607.24 pg\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) compared to naked DNA (135.69 pg\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ) or a liposomal Dc\u2010chol formulation (82.15 pg\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ). IFN\u03b3 expression in the lymph nodes was higher in the animals treated with gemini liposomes (422.74 pg\/animal) compared to the nanoemulsion formulation (131.27 pg\/animal) or the Dc\u2010chol formulation (82pg\/animal).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The feasibility of topical delivery of pGTmCMV.IFN\u2010GFP plasmid in mice using gemini cationic surfactant based delivery systems was demonstrated. IFN\u03b3 expression after treatment with gemini\u2013DNA formulations in the skin was 3\u20135\u2010fold higher compared to the treatment with naked DNA (\n                      <jats:italic>p<\/jats:italic>\n                      &lt; 0.05), and 4\u20136\u2010fold higher than the Dc\u2010chol\u2013DNA complex, indicating a significant advance in topical DNA delivery across intact skin\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Copyright \u00a9 2005 John Wiley &amp; Sons, Ltd.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jgm.763","type":"journal-article","created":{"date-parts":[[2005,5,16]],"date-time":"2005-05-16T06:46:32Z","timestamp":1116225992000},"page":"1200-1214","source":"Crossref","is-referenced-by-count":104,"title":["<i>In vivo<\/i>\n                    cutaneous interferon\u2010\u03b3 gene delivery using novel dicationic (gemini) surfactant\u2013plasmid 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