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Sesamol, a natural antioxidant with anticancer potential, faces challenges of low skin permeability. Transfersomes offer a promising strategy to enhance transdermal delivery. The present study aimed to formulate and optimize a phospholipid\u2010enriched sesamol\u2010loaded transfersome (SM\u2010TF) for breast cancer management.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The optimized formulation (Opt\u2010SM\u2010TF) exhibited a vesicle size of 184.8\u2009\u00b1\u20093.4\u2009nm with a polydispersity of 0.229\u2009\u00b1\u20090.01, as well as an entrapment efficiency of 90.23\u2009\u00b1\u20092.8% and zeta potential of \u221223.43\u2009\u00b1\u20092.80\u2009mV.\n                      <jats:italic>In vitro<\/jats:italic>\n                      release studies demonstrated significantly higher drug release from Opt\u2010SM\u2010TF (82.08\u2009\u00b1\u20093.04%) compared to sesamol suspension (40.96\u2009\u00b1\u20092.09%) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Antioxidant activity of Opt\u2010SM\u2010TF (79.65\u2009\u00b1\u20091.86%) surpassed that of sesamol solution (62.86\u2009\u00b1\u20091.52%) and was comparable to the reference standard ascorbic acid (88.40\u2009\u00b1\u20092.83%). Following incorporation into a Carbopol\u2010based gel (Opt\u2010SM\u2010TFG), key parameters such as spreadability, extrudability, pH and texture were assessed.\n                      <jats:italic>Ex vivo<\/jats:italic>\n                      permeation and confocal studies demonstrated 2.2\u2010folds higher permeation and deeper skin penetration (60\u2009\u03bcm\n                      <jats:italic>versus<\/jats:italic>\n                      20\u2009\u03bcm) for Opt\u2010SM\u2010TFG compared to sesamol suspension gel (SM\u2010SUSG) (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001).\n                      <jats:italic>In vitro<\/jats:italic>\n                      cytotoxicity on MCF\u20107 (i.e. Michigan Cancer Foundation\u20107) breast cancer cells revealed significantly greater cytotoxic (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) and a marked increase in superoxide dismutase activity (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001) for Opt\u2010SM\u2010TFG. Furthermore, levels pro\u2010inflammatory cytokine (interleukin\u20102, interleukin\u20106 and tumor necrosis factor\u2010\u03b1) were significantly downregulated in Opt\u2010SM\u2010TFG (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001 and\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>\n                      Opt\u2010SM\u2010TFG demonstrated superior skin permeation, antioxidant, anticancer and anti\u2010inflammatory potential compared to suspension gel, highlighting its promise as an effective transdermal platform for breast cancer therapy, warranting further\n                      <jats:italic>in vivo<\/jats:italic>\n                      and clinical evaluation. \u00a9 2025 Society of Chemical Industry.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jsfa.70381","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T07:15:22Z","timestamp":1765955722000},"page":"2830-2846","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Sesamol loaded transfersome gel for transdermal administration: novel approach for breast cancer therapy"],"prefix":"10.1002","volume":"106","author":[{"given":"Ahmed I.","family":"Foudah","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy Prince Sattam Bin Abdulaziz University  Al\u2010Kharj Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talha","family":"Jawaid","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, College of Medicine Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh Saudi 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