Cyclodextrin regulates the binding of quercetin to plasma proteins: Potentially enhancing bioavailability and efficacy

The relatively low bioavailability of hydrophobic polyphenols limits their efficacy. Additionally, their weak binding affinity to plasma proteins in systemic circulation reduces their ability to target specific sites within the human body. In this study, the potential of using cyclodextrins as modulators of polyphenol-plasma protein binding interactions was investigated. Quercetin (QUE) and human serum albumin (HSA) were used as models for hydrophobic polyphenols and plasma proteins, respectively. Binding parameters indicated a relatively weak affinity (Ka = 2.95 × 10 4  L mol −1 ) between QUE and HSA, suggesting rapid excretion and reduced bioactivity. Octenyl succinic acid-modified cyclodextrin (OSACD) enhanced the binding of QUE to HSA and increased the number of binding sites, thereby modulating its interaction more effectively than β-cyclodextrin (βCD) and succinic acid-modified cyclodextrin (SACD). Synchronous fluorescence spectroscopy revealed that QUE predominantly affected tryptophan residues, while cyclodextrins modified the microenvironment, with OSACD showing the most significant effect. Circular dichroism analysis demonstrated that cyclodextrins, particularly OSACD, mitigated the structural alterations induced by QUE, preserving the α-helix content of HSA. Stability tests showed that OSACD-encapsulated QUE retained 99.01% after UV exposure and higher retention rates after pasteurization and boiling compared to free QUE. Gastrointestinal simulation demonstrated enhanced release rates: QUE-OSACD (59.82%) surpassed QUE-SACD (46.38%), QUE-βCD (40.41%), and free QUE (14.09%). These findings underscore the efficacy of OSACD in stabilizing and improving the bioavailability of QUE, thereby enhancing its potential as a nutraceutical for incorporation into food products and other applications.