{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T22:27:30Z","timestamp":1789424850837,"version":"build-2803163510"},"reference-count":91,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    The present study aimed to prepare solid lipid-based nanoparticles (SLNs) using Precirol\n                    <jats:sup>\u00ae<\/jats:sup>\n                    ATO 5 as solid lipid and Poloxamer 188 and Tween 80 as surfactant and co-surfactant respectively, and SLNs-derived gel for sustained delivery, enhanced\n                    <jats:italic>in-vitro<\/jats:italic>\n                    cytotoxicity, enhanced cellular uptake of 5-FU and enhanced permeation of 5-FU across the skin. The 5-FU-loaded SLNs were prepared by the hot melt encapsulation method and converted into SLN-derived gel using a gelling agent (Carbopol 940). The 5-FU-loaded SLNs had a particle size in the range of 76.82\u00b11.48 to 327\u00b14.46 nm, zeta potential between -11.3\u00b12.11 and -28.4\u00b12.40 mV, and entrapment efficiency (%) in range of 63.46\u00b11.13 and 76.08\u00b12.42. The FTIR analysis depicted that there was no chemical interaction between 5-FU and formulation components. Differential scanning calorimetric analysis showed thermal stability of 5-FU in the nanoparticles and powdered X-ray diffraction analysis revealed successful incorporation of 5-FU in nanoparticles. The\n                    <jats:italic>in-vitro<\/jats:italic>\n                    release study of 5-FU-loaded SLNs showed biphasic release behavior with initial burst release followed by sustained release over 48 hr. The 5-FU-loaded SLNs showed a greater cytotoxic effect on skin melanoma (B16F10 cells) and squamous cell carcinoma (A-431 cells) as compared to free 5-FU drug solution after 48 hr. Flow cytometry and fluorescence microscopy displayed enhanced quantitative and qualitative cellular uptake of SLNs. The SLNs formulation showed acceptable safety and biocompatible profile after an acute toxicity study in Wistar rats. Moreover,\n                    <jats:italic>ex-vivo<\/jats:italic>\n                    permeation studies depicted 2.13\u00b10.076 folds enhanced flux of 5-FU-loaded SLN derived gel compared to 5-FU plain gel, and skin retention studies revealed target efficiency (%) 2.54\u00b10.03 of 5-FU-loaded SLN derived gel compared to 5-FU plain gel.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0281004","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T14:46:41Z","timestamp":1677595601000},"page":"e0281004","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Solid lipid-based nanoparticulate system for sustained release and enhanced in-vitro cytotoxic effect of 5-fluorouracil on skin Melanoma and squamous cell carcinoma"],"prefix":"10.1371","volume":"18","author":[{"given":"Ahsan","family":"Ali","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0388-9867","authenticated-orcid":true,"given":"Asadullah","family":"Madni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Talha","family":"Jamshaid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nasrullah","family":"Jan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safiullah","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Muzamil","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Ahmad","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"pone.0281004.ref001","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.plipres.2016.08.005","article-title":"Liposomal systems as viable drug delivery technology for skin cancer sites with an outlook on lipid-based delivery vehicles and diagnostic imaging inputs for skin conditions\u2019","volume":"64","author":"N Akhtar","year":"2016","journal-title":"Progress in lipid research"},{"issue":"4","key":"pone.0281004.ref002","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3390\/gels7040218","article-title":"Site-specific vesicular drug delivery system for skin cancer: a novel approach for targeting","volume":"7","author":"M 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