{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T13:24:37Z","timestamp":1794230677569,"version":"4.9.0"},"reference-count":60,"publisher":"American Chemical Society (ACS)","issue":"11","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Fulvestrant (FLV) is a selective estrogen receptor degrader used for hormone receptor-positive breast cancer. Nevertheless, its delivery is limited by low aqueous solubility and repeated intramuscular administration. Considering these drawbacks, a high-permeation vesicle-in-gel system (HPV-gel) was explored as a localized transdermal approach for FLV and evaluated for its physicochemical, permeation, cellular, pharmacokinetic, antitumor, and safety performance. Accordingly, FLV\/HPVs were prepared using soya phosphatidylcholine and a ternary permeation-enhancer combination of sodium oleate (SO), diethylene glycol monoethyl ether (DEGEE), and propylene glycol (PG). Enhancer proportions were optimized using a D-optimal mixture design based on vesicle size, PDI, and entrapment efficiency. The optimized composition contained 80% phospholipid and 20% of a permeation enhancer mixture, comprising SO, DEGEE, and PG in a ratio of 6:1.5:2.5. FLV\/HPVs showed a particle size of 94.02 \u00b1 1.10 nm, a PDI of 0.241 \u00b1 0.029, a zeta potential of \u201338.6 \u00b1 1.2 mV, an entrapment efficiency of 85.79 \u00b1 3.72%, a practical drug loading of 8.58 \u00b1 0.16%, and a deformability index of 1.62 \u00b1 0.08. The optimized vesicles were incorporated into a 1.5% w\/v Carbopol 934P gel and compared with FLV-gel and FLV\/Lipo-gel with the same gel base and an equivalent FLV amount. FLV\/HPVs-gel showed sustained drug release and increased FLV permeation by nearly 8-fold and 3-fold compared with FLV-gel and FLV\/Lipo-gel, respectively, with higher intradermal retention and deeper dermal distribution. Following topical administration, FLV\/HPVs-gel increased Cmax by \u223c8.3- and \u223c2-fold and AUC0-168 h by \u223c8.1- and \u223c2.6-fold compared with FLV-gel and FLV\/Lipo-gel, respectively, while showing plasma concentration\u2013time profile closer to FLV (i.m.). In 4T1 tumor-bearing mice, FLV\/HPVs-gel showed the strongest tumor-suppressive effect, accompanied by greater intratumoral penetration, while biochemical parameters, major organ histology, TEWL, and skin histology indicated acceptable systemic and local safety. Overall, FLV\/HPVs-gel improved skin permeation, drug exposure, and antitumor activity, suggesting its potential as a noninvasive transdermal approach for FLV in breast cancer therapy.<\/jats:p>","DOI":"10.1021\/acsbiomaterials.6c01112","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T20:01:25Z","timestamp":1792526485000},"page":"6226-6244","source":"Crossref","is-referenced-by-count":0,"title":["Potentiated Skin Permeation and Antitumor Efficacy of Fulvestrant-Loaded High-Permeation Vesicles for Localized Breast Cancer Treatment"],"prefix":"10.1021","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6619-167X","authenticated-orcid":true,"given":"Junia","family":"Akhtar","sequence":"first","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research (NIPER) , , Sector 67, S.A.S. Nagar , , ,","place":["Mohali, Punjab, India, 160062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-0932-5337","authenticated-orcid":true,"given":"Brojendra Nath","family":"Saren","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research (NIPER) , , Sector 67, S.A.S. Nagar , , ,","place":["Mohali, Punjab, India, 160062"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Yadav","sequence":"additional","affiliation":[{"name":"National Institute of Pharmaceutical Education and Research (NIPER) , , Sector 67, S.A.S. 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