{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:08:27Z","timestamp":1790806107332,"version":"4.1.0"},"reference-count":137,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Breast cancer remains one of the leading causes of cancer-related mortality. Still, limited drug delivery systems for genistein, a powerful natural anticancer agent, draw significant attention. We aimed to develop a co-therapeutic\/synergistic dual-compartment system; genistein-loaded pumpkisome nanovesicles (GNS-PKs) incorporated into pullulan microneedle patches (MNs), and to explore its anticancer activity. Methods: GNS-PKs were prepared and characterized for particle size (P.S), polydispersity (PDI), zeta potential (Z.P), encapsulation efficiency (E.E%), and stability. Afterward, they were embedded in pullulan-dissolving microneedle arrays and characterized for release kinetics, mechanical strength, and in vitro cytotoxicity. The in vivo efficacy was evaluated in mice with solid Ehrlich Ascites Carcinoma (EAC), focusing on tumor volume, oxidative stress, inflammatory cytokines, Epidermal Growth Factor (EGFR) expression biomarkers, and histopathological analysis. Results: The optimized nanovesicles had a particle size of 170 nm, a zeta potential of \u221242 mV, and an entrapment efficiency of up to 92%. Pullulan microneedles demonstrated significantly high mechanical strength and effective deep penetration. In addition to, it markedly decreased MCF-7 cellular viability (IC50 = 3.5 \u00b5g\/mL). Besides, it had a 76% reduction in tumor volume, significantly increased the antioxidant activity (SOD, CAT, GSH), decreased the levels of inflammatory biomarkers (IL-6, COX-2, NF-\u03baB), and markedly downregulated the EGFR expression (p &lt; 0.0001). Histological study revealed decreased mitotic activity and large tumor cells, with minimal systemic damage. Conclusions: GNS-PKs-pullulan microneedle system offers a hope for an innovative, potent, effective, and non-invasive strategy for breast cancer treatment with high antitumor efficacy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010036","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T06:25:51Z","timestamp":1766989551000},"page":"36","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Harnessing Dual Power: Genistein-Loaded Pumpkisomes in Pullulan Microneedles for Potent Antioxidant and Anticancer Therapy Against Ehrlich Ascites Carcinoma and Breast Cancer Cells"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-2288","authenticated-orcid":false,"given":"Sammar Fathy","family":"Elhabal","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Modern University for Technology and Information (MTI), Mokattam, Cairo 11571, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"S. Shoela","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4442-9867","authenticated-orcid":false,"given":"Mohamed Fathi Mohamed","family":"Elrefai","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo 11591, Egypt"},{"name":"Department of Basic Medical Sciences, Faculty of Medicine, Aqaba Medical Sciences University, Aqaba 77110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3985-8931","authenticated-orcid":false,"given":"Fatma","family":"E. Hassan","sequence":"additional","affiliation":[{"name":"Medical Physiology Department, Faculty of Medicine, Cairo University, Kasr Alainy, Giza 11562, Egypt"},{"name":"Department of Physiology, General Medicine Practice Program, Batterjee Medical College, Jeddah 21442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5874-194X","authenticated-orcid":false,"given":"Suzan Awad AbdelGhany","family":"Morsy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt"},{"name":"Pathological Sciences Department, MBBS Program, Fakeeh College for Medical Sciences, Jeddah 21461, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1951-1877","authenticated-orcid":false,"given":"Wedian","family":"Younis Abdelgawad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Egyptian Drug Authority (Formerly National Organization for Drug Control and Research \u201cNODCAR\u201d), Giza 15301, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7970-3301","authenticated-orcid":false,"given":"Sahar","family":"K. Ali","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Zagazig University, Zagazig 44519, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Passant","family":"M. Mohie","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"M. Elsharkawy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tassneim M.","family":"Ewedah","sequence":"additional","affiliation":[{"name":"Pharmaceutics and Pharmaceutical Technology Department, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim S.","family":"Mousa","sequence":"additional","affiliation":[{"name":"Pharmaceutics Department, Faculty of Pharmacy, Sinai University, Al-Arish 45511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0598-9028","authenticated-orcid":false,"given":"Marwa A.","family":"Fouad","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Deraya University, Minia 61768, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5633-4128","authenticated-orcid":false,"given":"Shady","family":"Allam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia University, Menoufia 32811, Egypt"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Menoufia National University, Cairo-Alexandria Agricultural Road, Menoufia 32511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4930-792X","authenticated-orcid":false,"given":"Ahmed Mohsen Elsaid","family":"Hamdan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"},{"name":"Prince Fahad bin Sultan Chair for Biomedical Research (PFSCBR), Tabuk 74191, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Elhabal, S.F., Mohammed Ali, E., Hababeh, S., Hassan, F.E., Morsy, S.A.A.G., Ahmed Elbahy, D., Ali, S.K., Allam, K.M., Mousa, I., and Fouad, M.A. (2025). 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