Synthesis, characterization, antioxidant activity of Quercetin, Rutin and Quercetin-Rutin incorporated β-cyclodextrin inclusion complexes and determination of their activity in NIH-3T3, MDA-MB-231 and A549 cell lines

•Q, R, and Q/R inclusion complexes were prepared with β-CD successfully both by solvent evaporation and lyophilization methods and detailed physicochemical characterization studies were carried out.•The aqueous solubility of Q and R were increased ∼29 fold and ∼35 fold, respectively with the help of complex formation.•According to the MTT analysis, the most affected cells in the Q and R loaded formulations even at the lowest dose (5 µM) were found to be MDA-MB-231 cells. While the effect of T4 was found to be high in A549 cells, dose-dependent cytotoxicity was detected among the other complexes and the studied cells.•T4 formulation containing Q showed the highest antioxidant activity according to DPPH analyses results. Complex formation did not influence the antioxidant activity of Q however for R remarkable degrease in antioxidant activity was detected.•Present study clearly demonstrated that β-CD is a suitable host to form inclusion complexes for Q and R. With enhanced water solubility enhanced bioavailability data of the incorporated agents will be achieved in pharmaceutical applications. Quercetin (Q) and rutin (R) are plant-originated polyphenolic flavonoids with considerably strong antioxidant and anticancer activity. Despite their potentials, low water solubility, stability problems and oral bioavailability limit their therapeutic use. The specific purpose of our study was to formulate inclusion complexes of Q and R with β-cyclodextrin (β-CD) to improve the solubility and also antioxidant activity of the flavonoids. Therefore 12 different complexes were prepared by both evaporation and lyophilization methods with 1:1 molar ratio in ethanol:water (1:1, v/v) solvent system. The characteristics of the complexes were also evaluated by yield%, zeta potential (ZP), entrapment efficiency (EE), 1H NMR, XRD, FT-IR, DSC analyses. In vitro dissolution studies were performed in comparison with pure substances. Antioxidant activity studies were carried out with DPPH tests. Cytotoxic evaluations of complexes were conducted with MTT tests on NIH 3T3, MDA-MB-231 and A549 cell lines. 1H- NMR analyses revealed the complex formation considering the shifts of the protons of the APIs as well as β-CD. ZP values were ranged between -21.20±0.56 mV and -7.10±0.62 mV. The aqueous solubility of Q and R were increased ∼29 fold and ∼35 fold, respectively. According to the MTT analyses results it has been shown that the flavonoids loaded complexes were particularly effective in