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Introduction <p>The nonpsychoactive cannabinoid cannabidiol (CBD) has shown a wide range of pharmacological effects that are&#xa0;beneficial for wound healing. However, its local delivery is challenged by a very low aqueous solubility.</p> Methods <p>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<sup>®&#xa0;</sup>F127 polymeric micelles (25% w/w payload).</p> Results <p>Hydrogels showed the typical porous structure (high resolution-scanning electron microscopy) and water uptake capacity up to ~ 1700%. The CBD release kinetics was studied in water (pH 6.8) and phosphate buffered saline (pH 7.4) under sink conditions, at 37°C. 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 &gt; 70% 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 days. 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.</p> Conclusion <p>Overall, results demonstrate the potential of levan hydrogels as platforms for local drug delivery applications.</p> Graphical Abstract <p></p>

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Natural Powerhouse Duo: Hierarchical Levan Hydrogels with Nanoencapsulated Cannabidiol as Local Delivery Systems

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年11月11日

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  • Diana Solovyov,
  • Natalia N. Porfiryeva,
  • Rania Awad,
  • Selay Tornaci,
  • Maya Davidovich-Pinhas,
  • Girts Salms,
  • Arita Dubnika,
  • Ebru Toksoy Öner,
  • Alejandro Sosnik

摘要

Introduction

The nonpsychoactive cannabinoid cannabidiol (CBD) has shown a wide range of pharmacological effects that are beneficial for wound healing. However, its local delivery is challenged by a very low aqueous solubility.

Methods

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® F127 polymeric micelles (25% w/w payload).

Results

Hydrogels showed the typical porous structure (high resolution-scanning electron microscopy) and water uptake capacity up to ~ 1700%. The CBD release kinetics was studied in water (pH 6.8) and phosphate buffered saline (pH 7.4) under sink conditions, at 37°C. 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 > 70% 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 days. 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.

Conclusion

Overall, results demonstrate the potential of levan hydrogels as platforms for local drug delivery applications.

Graphical Abstract