{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T18:35:23Z","timestamp":1724178923787},"reference-count":30,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2007,11,15]],"date-time":"2007-11-15T00:00:00Z","timestamp":1195084800000},"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":[[2008,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>All\u2010<jats:italic>trans<\/jats:italic> retinoic acid (ATRA) is a natural derivative of vitamin A, which is well known to suppress inflammatory cytokine production. To date, there have been few reports about the systemic use of ATRA for inflammation because of acute resistance and the highly lipophilic nature of ATRA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ATRA\u2010lipoplexes were prepared by mixing CMV\u2010Luc plasmid DNA with ATRA\u2010incorporated 1,2\u2010dioleoyl\u20103\u2010trimethylammoniopropane (DOTAP)\/cholesterol liposome. After intravenous injection, tissue accumulation, transfection efficacy, NF\u03baB activation, cytokine production, and hepatic toxicity of ATRA\u2010lipoplexes were evaluated and compared with lipoplexes lacking ATRA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The particle size and zeta potential of ATRA\u2010lipoplexes were similar to those of lipoplexes. After intravenous injection of ATRA\u2010lipoplexes, tissue accumulation in liver and gene expression in liver and lung were similar to those of lipoplexes, supporting the hypothesis that ATRA incorporation did not affect the delivery and gene transfection efficacy. In addition, ATRA incorporated in ATRA\u2010lipoplexes was delivered to liver in a manner similar to that for ATRA incorporated in liposomes. In addition, intravenous injection of ATRA\u2010lipoplexes inhibited the activation of NF\u03baB in liver, and subsequently suppressed the serum levels of tumor necrosis factor\u2010alpha (TNF\u2010\u03b1) and alanine aminotransferase (ALT) compared with lipoplexes. Liver histology data also demonstrated a low degree of liver injury produced by ATRA\u2010lipoplexes compared with lipoplexes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>ATRA\u2010incorporated lipoplexes effectively suppress NF\u03baB activation, cytokine response and liver injury induced by lipoplexes without affecting gene delivery and transfection efficacy <jats:italic>in vivo<\/jats:italic>. Copyright \u00a9 2007 John Wiley &amp; Sons, Ltd.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.1117","type":"journal-article","created":{"date-parts":[[2007,11,15]],"date-time":"2007-11-15T10:49:02Z","timestamp":1195123742000},"page":"61-69","source":"Crossref","is-referenced-by-count":9,"title":["Incorporation of all\u2010<i>trans<\/i> retinoic acid into lipoplexes inhibits nuclear factor \u03baB activation mediated liver injury induced by lipoplexes in 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