Physicochemical and structural characterization of quercetin-beta-cyclodextrin complexes.
Quercetin is a bioactive flavonoid widely used as a health supplement. Being sparingly soluble and chemically unstable in aqueous intestinal fluids, quercetin is poorly absorbed orally. This study aimed to investigate the effects of three beta-cyclodextrins, namely, unsubstituted beta-cyclodextrin (beta-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD), and sulfobutyl ether beta-cyclodextrin (SBE-beta-CD) on the chemical stability and water solubility of quercetin, and to elucidate the complexation mechanisms of these beta-CDs with quercetin. Quercetin-beta-CD complexes in solution were characterized by stability assessment, phase solubility measurements, and 1H-nuclear magnetic resonance (NMR) spectroscopy. Molecular modeling was used to help establish the mode of interaction of the beta-CDs with quercetin. Solubility enhancements of quercetin obtained with the three beta-CDs followed the rank order: SBE-beta-CD > HP-beta-CD > beta-CD. The stability of quercetin at alkaline pHs also showed substantial improvement. NMR spectroscopic analysis suggested that the B-ring, C-ring, and part of the A-ring of quercetin display favorable interaction with the hydrophobic cavity of the beta-CDs, which was confirmed by molecular dynamics (MD) simulations using a solvated model of the quercetin-beta-CD complex. An inclusion complex model has been established for explaining the observed augmentation of solubility and stability of quercetin in water by beta-CDs.
Zheng
Ying
Y
School of Pharmacy, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Haworth
Ian S
IS
Zuo
Zhong
Z
Chow
Moses S S
MS
Chow
Albert H L
AH
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011794:Quercetin / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D014867:Water; D047392:beta-Cyclodextrins / Q000737:chemistry*
D007202:Indicators and Reagents; D047392:beta-Cyclodextrins; D014867:Water; D011794:Quercetin; C031215:betadex