{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:00:04Z","timestamp":1787162404210,"version":"build-2736575974"},"reference-count":122,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Centre Poland","award":["OPUS UMO-2020\/37\/B\/NZ7\/03975"],"award-info":[{"award-number":["OPUS UMO-2020\/37\/B\/NZ7\/03975"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Apigenin (AP) is a natural flavonoid with senomorphic potential and neuroprotective action; however, poor aqueous solubility (&lt;1 \u03bcg\/mL) limits its bioavailability and therapeutic use. Therefore, the aim of this study was to obtain an amorphous dispersion of AP and evaluate its biological properties. Screening of AP solubilization capabilities under supercritical carbon dioxide processing conditions showed that the system with Soluplus (SOL) achieved the greatest improvement in AP dissolution (6455.4 \u00b1 27.2 \u03bcg\/mL). Using optimized process parameters (50 \u00b0C, 6500 PSI), the AP solubility increased to 8050.2 \u00b1 35.1 \u03bcg\/mL. X-ray powder diffraction (XRPD) confirmed amorphization, aligning with improved dissolution of AP in both acidic and neutral pH media. As a result, using the PAMPA model, an improvement in AP penetration through membranes simulating gastrointestinal and blood\u2013brain barriers was demonstrated. The significant stability of the obtained amorphous AP dispersion (12 months at room conditions) was associated with stabilizing AP\u2013solubilizer intermolecular interactions, mainly expressed as the shifts in the bands of AP in the range of 1018\u20131269 cm\u22121 observed in ATR-FT-IR spectra. Chromatographic analysis confirmed the lack of AP decomposition immediately after the preparation of the amorphous dispersion, as well as after 12 months. As expected, the improvement of AP solubility is correlated with better biological activity assessed in selected in vitro tests such as antioxidant properties (2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2\u2032-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and cupric ion reducing antioxidant capacity (CUPRAC) assays) and anticholinesterase inhibition capabilities (AChE and BChE assays). The effect of the studies on improving AP solubility under supercritical carbon dioxide processing conditions is obtaining a stable amorphous AP dispersion (up to 12 months). Regardless of the pH of the media, an improvement in AP dissolution and penetration, conditioned by the passive diffusion process, through biological membranes was noted. Moreover, a more efficient antioxidant and neuroprotective effect of AP in the developed amorphous dispersion can also be suggested.<\/jats:p>","DOI":"10.3390\/ijms26178126","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T12:31:26Z","timestamp":1755865886000},"page":"8126","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effective and Stable Senomorphic Apigenin Delivery System Obtained by Supercritical Carbon Dioxide Processing"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5211-661X","authenticated-orcid":false,"given":"Anna","family":"Stasi\u0142owicz-Krzemie\u0144","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str., 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4722-6413","authenticated-orcid":false,"given":"Natalia","family":"Rosiak","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str., 60-806 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7827-0663","authenticated-orcid":false,"given":"Giuseppe Francesco","family":"Racaniello","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Pharmaceutical Sciences, University of Bari Aldo Moro, Orabona St. 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-7828","authenticated-orcid":false,"given":"Nunzio","family":"Denora","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\u2014Pharmaceutical Sciences, University of Bari Aldo Moro, Orabona St. 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0891-5419","authenticated-orcid":false,"given":"Judyta","family":"Cielecka-Piontek","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy and Biomaterials, Poznan University of Medical Sciences, Rokietnicka 3 Str., 60-806 Poznan, Poland"},{"name":"Department of Pharmacology and Phytochemistry, Institute of Natural Fibres and Medicinal Plants, Wojska Polskiego 71b, 60-630 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"ref_1","first-page":"884","article-title":"Response of Global Health Towards the Challenges Presented by Population Aging","volume":"5","author":"Hong","year":"2023","journal-title":"China CDC Wkly."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Roger, L., Tomas, F., and Gire, V. 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