{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:50:13Z","timestamp":1785423013477,"version":"3.56.0"},"reference-count":87,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The cannabidiol (CBD)-rich cannabis extract CAN296 shows anti-inflammatory and anticancer activity relevant to oral lichen planus (OLP), oral graft-versus-host disease (oGVHD), and oral squamous cell carcinoma (OSCC), but its high lipophilicity limits aqueous dispersion. This study developed a stable Tween-based nanoemulsion optimized for oral mucosal delivery. Ethanol-dissolved CAN296 was nanoemulsified using a 1% Tween\/Span system. Physical stability was visually assessed; droplet size and morphology were examined by dynamic light scattering (DLS) and transmission electron microscopy (TEM); and wettability was measured by static contact angle (SCA). Additional evaluations included temperature stability (25 \u00b0C vs. 4 \u00b0C), in vitro release using a dialysis membrane, and scanning electron microscopy (SEM) of membrane-associated droplets. Nanoemulsions with \u226580% Tween 80 incorporated CAN296 up to 800 \u00b5g\/mL, clear at 400 \u00b5g\/mL, and uniformly turbid at 800 \u00b5g\/mL. DLS and TEM confirmed spherical nanoscale droplets, and SCA indicated favorable cohesion and wettability. Stability was maintained for 30 days at 4 \u00b0C. Dialysis studies demonstrated strong membrane association with limited diffusion, supported by SEM visualization of membrane-bound droplets. The Tween-dominant (\u226580%) nanoemulsion stably incorporated CAN296 up to 800 \u00b5g\/mL, demonstrated nanoscale uniformity, improved 4 \u00b0C stability, and strong membrane retention under static conditions, suggesting potential for localized oral delivery.<\/jats:p>","DOI":"10.3390\/ijms262311525","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T16:31:52Z","timestamp":1764261112000},"page":"11525","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and Characterization of a High-CBD Cannabis Extract Nanoemulsion for Oral Mucosal Delivery"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5319-0747","authenticated-orcid":false,"given":"Kifah","family":"Blal","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, Faculty of Dental Medicine, Hebrew University of Jerusalem, Jerusalem 9112102, Israel"},{"name":"School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgette","family":"Maroukian","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3701-9442","authenticated-orcid":false,"given":"Anna","family":"Shapira","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiri","family":"Procaccia","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7627-1569","authenticated-orcid":false,"given":"David","family":"Meiri","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Biology and Natural Drug Discovery, Faculty of Biology, Technion\u2014Israel Institute of Technology, Haifa 3200003, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2468-5978","authenticated-orcid":false,"given":"Ofra","family":"Benny","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 9112001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1089\/can.2018.0073","article-title":"Immune Responses Regulated by Cannabidiol","volume":"5","author":"Nichols","year":"2020","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1016\/j.bmc.2015.01.059","article-title":"Cannabidiol (CBD) and its analogs: A review of their effects on inflammation","volume":"23","author":"Burstein","year":"2015","journal-title":"Bioorg Med. 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