Cyclodextrin-Based Delivery Systems for Flavonoids: Mechanisms, Advances, Formulation, and Application Opportunities

In this review the structural characteristics and complexation mechanisms of various flavonoid-cyclodextrin complexes were summarized and their influence on biological activity was examined. Flavonoids due to their antioxidant properties play an important role in prevention and therapy —in areas such as neurodegenerative diseases, inflammation, and cancer—. Due to their pharmacokinetic drawbacks, such like poor water-solubility and low bioavailability their application is limited. To solve this problem, cyclodextrin can be used to form stable, water-soluble inclusion complexes, improving not only their solubility but also antioxidant activity. The aim of this review is to provide a comprehensive overview of the role of cyclodextrin-based carriers in the formulation of flavonoids and to highlight the future potential of these systems in modern therapeutics and functional product development.

The study presents in detail the structural characteristics of various flavonoid-cyclodextrin complexes, the mechanisms of complex formation, and their effect on antioxidant capacity. Special attention is given to nanotechnological formulations (e.g., liposomes, nanorods, nanosponges) that enable targeted drug delivery and increased therapeutic efficacy at various administration routes.

Some take-home messages:

•  If the solubility of the flavonoid is the limiting factor, cyclodextrin complexation typically enhances the antioxidant capacity by allowing more molecules to react with free radicals.
• CD-complexed antioxidants retained their radical scavenging ability is longer than the uncomplexed control.
• In the cyclodextrin complex, new intermolecular hydrogen bonds are formed between the hydroxy groups of CD and the flavonoid, this way weakening the intramolecular H-bonds, so flavonoids-donate hydrogen to free radicals more easily, thereby increasing their antioxidant efficiency.
• Flavonoids are increasingly being investigated as anticancer agents due to their prooxidant effects. 
• The influence of cyclodextrins on the prooxidant or antioxidant effects of flavonoids depends on the specific flavonoid, the type of cyclodextrin, and the environment.

Fenyvesi, F.; Klusóczki, Á.; Rusznyák, Á.; Zsebik, B.; Bácskay, I.; Váradi, J. Cyclodextrin-Based Delivery Systems for Flavonoids: Mechanisms, Advances, Formulation, and Application Opportunities. Antioxidants 2025, 14, 998. https://doi.org/10.3390/antiox14080998