An efficient design strategy for flavonoid co-amorphous systems and enhanced their antioxidant and antibacterial activities for application potential in food preservation and functional products

Flavonoids are the functional ingredients in human diets, but their generally low water solubility limits their therapeutic application. The study aimed to provide a new design and solubilization strategy for flavonoids co-amorphized with food-safe chlorogenic acid (CHL) by integrating theory-model-experiment techniques. Among 14 flavonoid candidates, 5 flavonoids might form co-amorphous systems with CHL through theoretical calculation and molecular dynamics (MD) simulation. Co-amorphization accuracy was further confirmed by practical preparation and characterizations. Meanwhile, potential hydrogen-bond interactions occurred in the formed co-amorphous systems via FTIR and MD analyses. Herein, 5 flavonoid co-amorphous systems displayed significantly enhanced solubility/dissolution and excellent physical stability. Additionally, such co-amorphous systems performed strong antioxidant activity according to DPPH radical scavenging, and possessed superior antibacterial activity than flavonoids themselves against three kinds of bacteria. This study emphasizes that the integrated strategy can be used to design flavonoid co-amorphous systems for enhancing their antioxidant and antibacterial activities in food preservation and functional products. Importantly, this study provides a practical methodology to guide the screening of co-amorphous systems for flavonoid components and even other classes of compounds by integrating theory-model-experiment techniques.