Development of Morin‐Loaded Hydrogel as a Bioactive Platform for Potential Topical Applications: Experimental and Theoretical Analysis of Drug–Polymer Interactions

Topical delivery systems represent a promising strategy to reduce adverse effects associated with conventional therapies devoted to the treatment of skin disorders. This study deals with the fabrication of a biopolymeric platform for topical delivery of morin (M), a bioactive flavonoid with antioxidant and anticancer properties. Hydrogels based on gelatin (G), chitosan (Ch), and arabic gum (AG) were synthesized by freeze–thaw method. M was loaded to impart the therapeutic action. Characterization of hydrogels demonstrated that Ch incorporation improved mechanical and thermal properties, swelling, and water stability. Two loading methods were explored to incorporate M: surface adsorption and drug encapsulation during gel formation. The reached efficiencies were 42% and 100% for adsorption and encapsulation, respectively. Antioxidant activity, evaluated by scavenging DPPH radicals (%), was also enhanced by M loading reaching 45% versus 22% when the raw hydrogel was assayed. In vitro cytotoxicity studies confirmed the biosafety of formulations. Drug release experiments showed that 65% of M was released from hydrogel after 120 min in a skin‐simulating medium. Molecular simulations were performed to justify the M retention. The achieved findings highlight the critical role of molecular‐level interactions in governing M release, providing guidelines for the development of hydrogel‐based topical delivery systems.