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However, its local delivery is challenged by a very low aqueous solubility.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In this work, we synthesized hierarchical hydrogels made of the fructan hydrolyzed levan crosslinked with glycerol diglycidyl ether and loaded them with CBD nanoencapsulated within Pluronic\n                      <jats:sup>\u00ae\u00a0<\/jats:sup>\n                      F127 polymeric micelles (25% w\/w payload).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hydrogels showed the typical porous structure (high resolution-scanning electron microscopy) and water uptake capacity up to\u2009~\u20091700%. The CBD release kinetics was studied in water (pH 6.8) and phosphate buffered saline (pH 7.4) under sink conditions, at 37\u00b0C. An initial burst release stage within the first 2 h of the assay was followed by a more sustained release stage over 72 h. As expected, hydrogels with a lower crosslinking density exhibited faster CBD release in both media. Release data fit the Korsmeyer-Peppas model with a combined mechanism involving diffusion and polymer chain relaxation together with the release of CBD-loaded polymeric micelles. The good compatibility of the hydrogels was initially confirmed in the monocyte-derived human macrophage cell line THP-1 over 72 h. Then, we showed\u2009&gt;\u200970% viability of primary patient-derived gingival mesenchymal stem cells (GMSCs) exposed to hydrolyzed levan solutions, CBD-loaded polymeric micelle suspensions, and the CBD-loaded hydrogels for 28\u202fdays. Finally, we conducted preliminary differentiation studies of GMSCs cultured on non-loaded and CBD-loaded hydrolyzed levan hydrogels. Non-loaded hydrogels promote a transient increase in the secretion of the osteogenic marker alkaline phosphatase secretion that peaked at day 7 and declined thereafter, while CBD-loaded ones promote adipogenic differentiation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Overall, results demonstrate the potential of levan hydrogels as platforms for local drug delivery applications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical Abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s11095-025-03935-y","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T19:51:04Z","timestamp":1762890664000},"page":"2291-2307","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Natural Powerhouse Duo: Hierarchical Levan Hydrogels with Nanoencapsulated Cannabidiol as Local Delivery Systems"],"prefix":"10.1007","volume":"42","author":[{"given":"Diana","family":"Solovyov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia N.","family":"Porfiryeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Awad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selay","family":"Tornaci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Davidovich-Pinhas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girts","family":"Salms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arita","family":"Dubnika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ebru Toksoy","family":"\u00d6ner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandro","family":"Sosnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"3935_CR1","doi-asserted-by":"crossref","unstructured":"Sharma A, Shankar R, Kumar Yadav A, Pratap A, Ansari MA, Srivastava V. 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