{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T17:27:11Z","timestamp":1787074031685,"version":"build-2736575974"},"reference-count":107,"publisher":"American Chemical Society (ACS)","issue":"32","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009229","name":"American University in Cairo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009229","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Background: Proniosomes are anhydrous, free-flowing formulations that, upon hydration, yield niosomes-lipid-based vesicles. These biocompatible vesicles represent a promising vehicle for drug delivery in melanoma treatment. Methods: This study aimed to develop a melanoma therapy by combining the benefits of proniosomes with the reported anticancer activity of the natural phenolic compound Trans-ferulic acid (T-FA). Six formulations of T-FA-loaded-proniosomes (PrN-1 to PrN-6) were prepared and compared in terms of their physicochemical parameters, entrapment efficiency, and antioxidant activity. Additionally, cytotoxicity against melonoma cells and skin permeability of the proniosome-loaded-T-FA formulations were studied. Results: The optimized T-FA niosomal dispersions showed a %EE of 69.01%, zeta potential of 37.6 mV, PDI of 0.237, %TLC of 34.51%, and nanosized particles. The hydrated niosomal dispersions preserved the scavenging capacity of T-FA (SC50 of 11.34\u201312.17 \u03bcg\/mL). The T-FA- niosomal dispersions for PrN-1 (IC50 of 171.75 \u03bcg\/mL) and PrN-5 (IC50 of 41.58 \u03bcg\/mL) exhibited greater cytotoxicity on the A-375 melanoma cell line compared to free T-FA (IC50 of 275.06 \u03bcg\/mL). The in vitro release study showed a pH-sensitive and diffusion-based sustained release behavior. The permeability of T-FA from the proniosomal gel displayed optimum permeability coefficient and T-FA flux; PrN-2 (0.00379 \u00b1 0.0006 cm\/h and 7.586 \u00b1 0.11 \u03bcg\/cm2 h\u20131) and PrN-5 (0.00434 \u00b1 0.001 cm\/h and 8.69 \u00b1 0.13 \u03bcg\/cm2 h\u20131). Conclusion: The prepared proniosomal gels efficiently encapsulated T-FA, maintained its antioxidant properties, and enhanced its cytotoxic effects against A-375 melanoma cells.<\/jats:p>","DOI":"10.1021\/acsomega.6c01402","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:02:09Z","timestamp":1785934929000},"page":"47459-47472","source":"Crossref","is-referenced-by-count":0,"title":["Drug Delivery Investigation\nof Trans-Ferulic Acid\nLoaded Proniosomal Gels"],"prefix":"10.1021","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6771-7183","authenticated-orcid":true,"given":"Marwa","family":"Saady","sequence":"first","affiliation":[{"name":"The American University in Cairo , , AUC Avenue , P.O. Box 74, ,","place":["New Cairo, Egypt, 11835"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Maher","sequence":"additional","affiliation":[{"name":"The American University in Cairo , , AUC Avenue , P.O. Box 74, ,","place":["New Cairo, Egypt, 11835"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2047-4222","authenticated-orcid":true,"given":"Hassan Mohamed El-Said","family":"Azzazy","sequence":"additional","affiliation":[{"name":"The American University in Cairo , , AUC Avenue , P.O. Box 74, ,","place":["New Cairo, Egypt, 11835"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"2026081810485597800_cit1","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1186\/s12943-023-01854-3","article-title":"Skin cancer: understanding the journey of transformation\nfrom conventional to advanced treatment approaches","volume":"22","author":"Hasan","year":"2023","journal-title":"Mol. Cancer"},{"key":"2026081810485597800_cit2","unstructured":"Ehlers, J.\n          \n          Cancer Statistics\nfor 2025 (2025). https:\/\/www.hematologyadvisor.com\/news\/cancer-statistics-for-2025\/. Accessed 4 June 2025."},{"key":"2026081810485597800_cit3","unstructured":"Melanoma of the Skin\n- Cancer Stat Facts.\u201d https:\/\/seer.cancer.gov\/statfacts\/html\/melan.html. Accessed 4 June 2025."},{"issue":"19","key":"2026081810485597800_cit4","doi-asserted-by":"publisher","first-page":"4652","DOI":"10.3390\/cancers14194652","article-title":"Melanoma Management:\nFrom Epidemiology to Treatment and Latest Advances","volume":"14","author":"Lopes","year":"2022","journal-title":"Cancers"},{"issue":"6","key":"2026081810485597800_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e17488","article-title":"Advances in drug delivery\nsystems, challenges and future directions","volume":"9","author":"Ezike","year":"2023","journal-title":"Heliyon"},{"issue":"1","key":"2026081810485597800_cit6","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s43094-020-00117-y","article-title":"Recent advances of non-ionic\nsurfactant-based nano-vesicles (niosomes\nand proniosomes): a brief review of these in enhancing transdermal\ndelivery of drug","volume":"6","author":"Db","year":"2020","journal-title":"Future J. Pharm. Sci."},{"key":"2026081810485597800_cit7","article-title":"Proniosomes: An\nEmerging Vesicular\nSystem in Drug Delivery and Cosmetics","volume":"2","author":"Kakar","year":"2009","journal-title":"Pharm.\nLett."},{"key":"2026081810485597800_cit8","doi-asserted-by":"publisher","first-page":"120163","DOI":"10.1016\/j.ijpharm.2020.120163","article-title":"Optimization\nof transdermal atorvastatin calcium \u2013 Loaded proniosomes: Restoring\nlipid profile and alleviating hepatotoxicity in poloxamer 407-induced\nhyperlipidemia","volume":"593","author":"Eltellawy","year":"2021","journal-title":"Int. J. Pharm."},{"key":"2026081810485597800_cit9","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1080\/10717544.2017.1384520","article-title":"Proniosomes derived\nniosomes: recent\nadvancements in drug delivery and targeting","volume":"24","author":"Khatoon","year":"2017","journal-title":"Drug Deliv"},{"key":"2026081810485597800_cit10","doi-asserted-by":"publisher","first-page":"100165","DOI":"10.1016\/j.ejmcr.2024.100165","article-title":"Novel synthesis\nof trans-ferulic acid loaded tragacanth-chitosan nanoformulations\nand evaluation of their biological activities","volume":"11","author":"Rani","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"issue":"5","key":"2026081810485597800_cit11","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.3390\/molecules30051018","article-title":"The Role of\nFerulic Acid in Selected Malignant Neoplasms","volume":"30","author":"Markowska","year":"2025","journal-title":"Molecules"},{"issue":"4","key":"2026081810485597800_cit12","article-title":"2-Methoxy-4-vinylphenol\ncan\ninduce cell cycle arrest by blocking the hyper-phosphorylation of\nretinoblastoma protein in benzo[a]pyrene-treated NIH3T3 cells","volume":"400","author":"Jb","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"issue":"12","key":"2026081810485597800_cit13","doi-asserted-by":"publisher","first-page":"6685","DOI":"10.21873\/anticanres.13883","article-title":"2-Methoxy-4-vinylphenol\nAttenuates Migration of Human Pancreatic Cancer Cells via Blockade\nof FAK and AKT Signaling","volume":"39","author":"Kim","year":"2019","journal-title":"Anticancer Res."},{"key":"2026081810485597800_cit14","doi-asserted-by":"publisher","DOI":"10.1590\/1678-4324-2023210265","article-title":"Gas Chromatography-Mass Spectrometry\nAnalysis and Antimicrobial\nand Antioxidant Activities of Some Orchid (Orchidaceae) Species Growing\nin Turkey","volume":"66","author":"Ertu\u0308rk","year":"2023","journal-title":"Braz. Arch. Biol. 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Biotechnol."},{"key":"2026081810485597800_cit16","doi-asserted-by":"publisher","first-page":"3716","DOI":"10.3390\/molecules30183716","article-title":"Ferulic Acid:\nMechanistic Insights and Multifaceted Applications in Metabolic Syndrome,\nFood Preservation, and Cosmetics","volume":"30","author":"Jacobo-Vela\u0301zquez","year":"2025","journal-title":"Molecules"},{"issue":"1","key":"2026081810485597800_cit17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.jsps.2014.05.001","article-title":"Penetration enhancers\nin proniosomes\nas a new strategy for enhanced transdermal drug delivery","volume":"23","author":"El","year":"2015","journal-title":"Saudi Pharm. J. SPJ."},{"key":"2026081810485597800_cit18","doi-asserted-by":"publisher","first-page":"105728","DOI":"10.1016\/j.jddst.2024.105728","article-title":"Engineered lecithin-based\nproniosomes for enhanced trans-tympanic permeation: In vitro, microbiological, ex vivo and in vivo evaluation","volume":"96","author":"Younes","year":"2024","journal-title":"J. Drug Delivery\nSci. Technol."},{"issue":"2","key":"2026081810485597800_cit19","doi-asserted-by":"publisher","first-page":"118","DOI":"10.3109\/08982104.2016.1167737","article-title":"Design\nand evaluation of proniosomes as a carrier for ocular delivery of\nlomefloxacin HCl","volume":"27","author":"Khalil","year":"2017","journal-title":"J. Liposome Res."},{"issue":"1","key":"2026081810485597800_cit20","doi-asserted-by":"publisher","first-page":"85","DOI":"10.3390\/antiox10010085","article-title":"Proniosomal Gel for\nTopical Delivery of Rutin: Preparation, Physicochemical Characterization\nand In Vitro Toxicological Profile Using 3D Reconstructed Human Epidermis\nTissue and 2D Cells","volume":"10","author":"Pinzaru","year":"2021","journal-title":"Antioxidants"},{"key":"2026081810485597800_cit21","doi-asserted-by":"publisher","first-page":"104820","DOI":"10.1016\/j.jddst.2023.104820","article-title":"Green extraction of\nessential oils from Pistacia lentiscus resins: Encapsulation\ninto Niosomes showed improved preferential cytotoxic and apoptotic\neffects against breast and ovarian cancer cells","volume":"87","author":"Fahmy","year":"2023","journal-title":"J. Drug Delivery Sci. Technol."},{"issue":"2\u20133","key":"2026081810485597800_cit22","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1081\/WCT-120013358","article-title":"Uv\u2013Vis.\nSpectroscopic Characteristics\nof Ferulic Acid and Related Compounds","volume":"22","author":"Pan","year":"2002","journal-title":"J. Wood\nChem. Technol."},{"issue":"1","key":"2026081810485597800_cit23","first-page":"66","article-title":"Development and Evaluation of Atorvastatin\nCalcium Nanovesicular Niosomal Gel for the Treatment of Periodontitis","volume":"56","author":"Kate","year":"2023","journal-title":"Eng. Proc."},{"issue":"2","key":"2026081810485597800_cit24","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1021\/acsabm.3c00700","article-title":"Functionalized Carbon\nNanotubes for Delivery of Ferulic Acid and Diosgenin Anticancer Natural\nAgents","volume":"7","author":"AbouAitah","year":"2024","journal-title":"ACS Appl. Bio Mater."},{"issue":"1","key":"2026081810485597800_cit25","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s11671-024-03962-5","article-title":"Synergistic anticancer effect of\nPistacia lentiscus essential oils and 5-Fluorouracil co-loaded onto\nbiodegradable nanofibers against melanoma and breast cancer","volume":"19","author":"Alabrahim","year":"2024","journal-title":"Discovery Nano"},{"key":"2026081810485597800_cit26","doi-asserted-by":"publisher","first-page":"101854","DOI":"10.1016\/j.jddst.2020.101854","article-title":"Development\nof trans-Ferulic acid\nniosome: An optimization and an in-vivo study","volume":"59","author":"Rezaeiroshan","year":"2020","journal-title":"J. Drug Delivery Sci. 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Methods"},{"issue":"1\u20132","key":"2026081810485597800_cit30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric\nassay for cellular growth and survival: application to proliferation\nand cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"2026081810485597800_cit31","doi-asserted-by":"publisher","first-page":"107848","DOI":"10.1016\/j.bioorg.2024.107848","article-title":"Discovery\nof novel diaryl urea-oxindole hybrids as\nBRAF kinase inhibitors targeting BRAF and KRAS mutant cancers","volume":"153","author":"Ghannam","year":"2024","journal-title":"Bioorganic Chem."},{"issue":"23","key":"2026081810485597800_cit32","doi-asserted-by":"publisher","first-page":"12827","DOI":"10.3390\/ijms222312827","article-title":"The MTT Assay: Utility,\nLimitations, Pitfalls, and Interpretation in Bulk and Single-Cell\nAnalysis","volume":"22","author":"Ghasemi","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"12","key":"2026081810485597800_cit33","doi-asserted-by":"crossref","first-page":"11271","DOI":"10.1039\/D5RA07949G","article-title":"Nanoencapsulation of Rhodiola rosea extract into 2-hydroxypropyl-\u03b2-cyclodextrin:\nenhanced antibacterial and anticancer activities","volume":"16","year":"2026","journal-title":"RSC Adv."},{"issue":"2","key":"2026081810485597800_cit34","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/S0928-0987(01)00095-1","article-title":"Modeling and comparison of dissolution\nprofiles","volume":"13","author":"Costa","year":"2001","journal-title":"Eur. J. Pharm. Sci. Off. J. Eur. Fed.\nPharm. Sci."},{"issue":"3","key":"2026081810485597800_cit35","first-page":"217","article-title":"Kinetic modeling\non drug release from controlled drug delivery systems","volume":"67","author":"Dash","year":"2010","journal-title":"Acta Polym. Pharm."},{"key":"2026081810485597800_cit36","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.jconrel.2017.03.039","article-title":"Transdermal\ndelivery of atorvastatin calcium from novel nanovesicular systems\nusing polyethylene glycol fatty acid esters: Ameliorated effect without\nliver toxicity in poloxamer 407-induced hyperlipidemic rats","volume":"254","author":"Mahmoud","year":"2017","journal-title":"J. Controlled Release"},{"key":"2026081810485597800_cit37","doi-asserted-by":"publisher","first-page":"119073","DOI":"10.1016\/j.ijpharm.2020.119073","article-title":"Boosting transdermal\ndelivery of atorvastatin calcium via o\/w nanoemulsifying system: Two-step\noptimization, ex vivo and in vivo evaluation","volume":"578","author":"Shaker","year":"2020","journal-title":"Int. J. 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(Cairo Univ.)"},{"issue":"1\u20132","key":"2026081810485597800_cit44","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/S0168-3659(99)00199-6","article-title":"Evaluation\nof novel soya-lecithin\nformulations for dermal use containing ketoprofen as a model drug","volume":"63","author":"Valenta","year":"2000","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"issue":"17","key":"2026081810485597800_cit45","doi-asserted-by":"publisher","first-page":"9668","DOI":"10.3390\/ijms23179668","article-title":"Current Advances in Specialised Niosomal\nDrug Delivery:\nManufacture, Characterization and Drug Delivery Applications","volume":"23","author":"Witika","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"4","key":"2026081810485597800_cit46","doi-asserted-by":"publisher","first-page":"243","DOI":"10.3109\/10717544.2013.841783","article-title":"A review on\nnovel vesicular drug delivery: proniosomes","volume":"21","author":"Yasam","year":"2014","journal-title":"Drug Deliv"},{"key":"2026081810485597800_cit47","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1515\/abm-2018-0002","article-title":"Niosomes:\nA review of their structure, properties, methods of preparation, and\nmedical applications","volume":"11","author":"Yeo","year":"2018","journal-title":"Asian Biomed."},{"issue":"1","key":"2026081810485597800_cit48","article-title":"The influence of the polar head and the hydrophobic\nchain on the\nskin penetration enhancement effect of poly(ethylene glycol) derivatives","volume":"13","author":"A","year":"2012","journal-title":"AAPS PharmSciTech"},{"key":"2026081810485597800_cit49","volume-title":"Inactive Ingredients Database Download","author":"Research C for DE and.","year":"2024"},{"issue":"3","key":"2026081810485597800_cit50","doi-asserted-by":"publisher","first-page":"782","DOI":"10.1208\/s12249-008-9114-0","article-title":"In Vitro\nEvaluation\nof Proniosomes as a Drug Carrier for Flurbiprofen","volume":"9","author":"Ibrahim","year":"2008","journal-title":"AAPS PharmSciTech"},{"issue":"4","key":"2026081810485597800_cit51","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1208\/s12249-010-9539-0","article-title":"Comparative Study\non the Effects\nof Some Polyoxyethylene Alkyl Ether and Sorbitan Fatty Acid Ester\nSurfactants on the Performance of Transdermal Carvedilol Proniosomal\nGel Using Experimental Design","volume":"11","author":"Aboelwafa","year":"2010","journal-title":"AAPS PharmSciTech"},{"key":"2026081810485597800_cit52","doi-asserted-by":"crossref","DOI":"10.3109\/10717544.2014.896428","article-title":"Formulation of tretinoin-loaded\ntopical proniosomes for treatment of acne: in-vitro characterization,\nskin irritation test and comparative clinical study","author":"Rahman","year":"2015","journal-title":"Drug Deliv"},{"issue":"8","key":"2026081810485597800_cit53","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.3109\/10717544.2013.870260","article-title":"Formulation\nby design-based proniosome for accentuated transdermal delivery of\nrisperidone: in vitro characterization and in vivo pharmacokinetic\nstudy","volume":"22","author":"Imam","year":"2015","journal-title":"Drug Deliv"},{"issue":"1","key":"2026081810485597800_cit54","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ejpb.2010.10.011","article-title":"Novel sugar\nesters proniosomes for\ntransdermal delivery of vinpocetine: preclinical and clinical studies","volume":"77","author":"El-Laithy","year":"2011","journal-title":"Eur. J. Pharm. Biopharm. Off. J. Arbeitsgemeinschaft Pharm.\nVerfahrenstechnik EV"},{"key":"2026081810485597800_cit55","doi-asserted-by":"publisher","first-page":"104972","DOI":"10.1016\/j.ejps.2019.104972","article-title":"Colloidal (\u2212)-epigallocatechin-3-gallate\nvesicular systems for prevention and treatment of skin cancer: A comprehensive\nexperimental study with preclinical investigation","volume":"137","author":"El-Kayal","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"2026081810485597800_cit56","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.molliq.2018.02.077","article-title":"Cholesterol\nconcentration effect\non the bilayer properties and phase formation of niosome bilayers:\nA molecular dynamics simulation study","volume":"256","author":"Somjid","year":"2018","journal-title":"J. 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