title: Physical properties and biological activities of hesperetin and naringenin in complex with methylated β-cyclodextrin.
abstract: The aim of this work is to improve physical properties and biological activities of the two flavanones hesperetin and naringenin by complexation with β-cyclodextrin (β-CD) and its methylated derivatives (2,6-di-O-methyl-β-cyclodextrin, DM-β-CD and randomly methylated-β-CD, RAMEB). The free energies of inclusion complexes between hesperetin with cyclodextrins (β-CD and DM-β-CD) were theoretically investigated by molecular dynamics simulation. The free energy values obtained suggested a more stable inclusion complex with DM-β-CD. The vdW force is the main guest-host interaction when hesperetin binds with CDs. The phase solubility diagram showed the formation of a soluble complex of AL type, with higher increase in solubility and stability when hesperetin and naringenin were complexed with RAMEB. Solid complexes were prepared by freeze-drying, and the data from differential scanning calorimetry (DSC) confirmed the formation of inclusion complexes. The data obtained by the dissolution method showed that complexation with RAMEB resulted in a better release of both flavanones to aqueous solution. The flavanones-β-CD/DM-β-CD complexes demonstrated a similar or a slight increase in anti-inflammatory activity and cytotoxicity towards three different cancer cell lines. The overall results suggested that solubilities and bioactivities of both flavanones were increased by complexation with methylated β-CDs.
authors.affiliation: Structural and Computational Biology Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Waratchada
authors.initials: W
authors.lastname: Sangpheak
authors.affiliation: Structural and Computational Biology Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Jintawee
authors.initials: J
authors.lastname: Kicuntod
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna 1090, Austria.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Schuster
authors.affiliation: Structural and Computational Biology Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; Ph.D. Program in Bioinformatics and Computational Biology, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Thanyada
authors.initials: T
authors.lastname: Rungrotmongkol
authors.affiliation: Structural and Computational Biology Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand; Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna 1090, Austria; Institute of Theoretical Chemistry, University of Vienna, Vienna 1090, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Wolschann
authors.affiliation: Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand.
authors.forename: Nawee
authors.initials: N
authors.lastname: Kungwan
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna 1090, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Vienna 1090, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Mueller
authors.affiliation: Starch and Cyclodextrin Research Unit, Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.
authors.forename: Piamsook
authors.initials: P
authors.lastname: Pongsawasdi
keywords: binding energy; bioactivity; cyclodextrins; hesperetin; naringenin