Camilo Zamora-Ledezma, Dulexy Solano-Orrala, Daniel Peña-Jimenez, Sandra Herranz-Gómez, Dennis A Silva-Cullishpuma, María Teresa Mercader-Ros, Giovanna Gomez d'Ayala, Donatella Duraccio, Duncan John Mowbray, Stephanie Marina Díaz-López, Frank Alexis, Carmen Lucas-Abellán
Agar/xanthan hydrogels incorporating hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complexes of nonpsychoactive cannabinoids (cannabidiol, CBD; cannabinol, CBN) were developed as multifunctional biomaterials for controlled delivery and antimicrobial soft-tissue biomedical applications. Physicochemical characterization showed improved thermal stability, tunable hydrophilicity, and a porous network suitable for loading and release. In vitro release studies demonstrated sustained cannabinoid delivery over 72 h, following first-order and Fu-Kao kinetic models. The hydrogels exhibited selective antimicrobial activity against Staphylococcus aureus, while remaining inactive toward Escherichia coli. Cytocompatibility assays with human skin fibroblasts confirmed noncytotoxic behavior over 7 days for all hydrogel formulations tested. These results highlight that cyclodextrin-cannabinoid-loaded agar/xanthan hydrogels are promising biocompatible platforms for controlled delivery with antimicrobial activity, suitable for tissue engineering applications.