{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:03:02Z","timestamp":1789790582695,"version":"4.0.1"},"reference-count":39,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre, Poland","doi-asserted-by":"publisher","award":["2022\/45\/B\/NZ7\/01056"],"award-info":[{"award-number":["2022\/45\/B\/NZ7\/01056"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded intravenous (IV) nanoemulsions using commercial lipid preparations with varying fatty acid compositions. The formulations were physicochemically characterized and evaluated in vitro using FaDu and SCC-040 HNSCC cell lines. HON and MAG were sterilized via ionizing radiation at doses of 25, 100, and 400 kGy. Their suitability for IV use was assessed through PXRD, DSC, TGA, EPR, FT-IR, NMR, and HPLC analyses. All formulations met safety criteria for IV administration, with mean droplet diameters below 241 nm and encapsulation efficiencies exceeding 95%. They significantly reduced cancer cell viability, with a synergistic effect observed in combined HON and MAG formulations compared to single-compound nanoemulsions. Clinoleic-based formulations showed enhanced anticancer efficacy, likely due to the pro-apoptotic properties of oleic acid. Notably, radiation sterilization at the standard 25 kGy dose preserved the thermal, crystalline, and structural stability of HON and MAG, whereas higher doses (400 kGy) induced degradation. Although free radicals were detected via EPR, their transient nature and rapid decay confirmed the method\u2019s safety. HON\/MAG-loaded nanoemulsions exhibited strong anticancer potential, while radiation sterilization at 25 kGy ensured sterility without compromising stability. These findings provide a preliminary in vitro basis for future in vivo studies investigating HON and MAG as potential adjuvant therapies for HNSCC.<\/jats:p>","DOI":"10.3390\/ijms26168032","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T08:02:44Z","timestamp":1755763364000},"page":"8032","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Formulation of Honokiol- and Magnolol-Loaded Nanoemulsions for Head and Neck Cancer Adjuvant Therapy: Evaluation of Radiation Sterilization Effects on Active Substance Properties"],"prefix":"10.3390","volume":"26","author":[{"given":"Katarzyna","family":"Dominiak","sequence":"first","affiliation":[{"name":"Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-9503","authenticated-orcid":false,"given":"Aleksandra","family":"Gosty\u0144ska-Stawna","sequence":"additional","affiliation":[{"name":"Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8651-4560","authenticated-orcid":false,"given":"Agnieszka","family":"Sobczak","sequence":"additional","affiliation":[{"name":"Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6187-7549","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Paluszczak","sequence":"additional","affiliation":[{"name":"Chair and Department of Pharmaceutical Biochemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-802 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneta","family":"Wo\u017aniak-Braszak","sequence":"additional","affiliation":[{"name":"Functional Materials Physics Division, Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Pozna\u0144skiego 2, 61-614 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miko\u0142aj","family":"Baranowski","sequence":"additional","affiliation":[{"name":"Functional Materials Physics Division, Faculty of Physics, Adam Mickiewicz University, Uniwersytetu Pozna\u0144skiego 2, 61-614 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Bilski","sequence":"additional","affiliation":[{"name":"Department of Experimental Physics of Condensed Phase, Faculty of Physics and Astronomy, Adam Mickiewicz University, Uniwersytetu Pozna\u0144skiego 2, 61-614 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2254-2508","authenticated-orcid":false,"given":"Barbara","family":"Wicher","sequence":"additional","affiliation":[{"name":"Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-802 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9393-3536","authenticated-orcid":false,"given":"Ewa","family":"Tykarska","sequence":"additional","affiliation":[{"name":"Department of Chemical Technology of Drugs, Poznan University of Medical Sciences, Rokietnicka 3, 60-802 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Jeli\u0144ska","sequence":"additional","affiliation":[{"name":"Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5106-5937","authenticated-orcid":false,"given":"Maciej","family":"Stawny","sequence":"additional","affiliation":[{"name":"Chair and Department of Pharmaceutical Chemistry, Poznan University of Medical Sciences, Rokietnicka 3, 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1055\/a-0642-1966","article-title":"Safety and Toxicology of Magnolol and Honokiol","volume":"84","author":"Sarrica","year":"2018","journal-title":"Planta Med."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Zhang, J., Chen, Z., Huang, X., Shi, W., Zhang, R., Chen, M., Huang, H., and Wu, L. 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