Abstract

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.