Host-guest inclusion system of oleanolic acid with methyl-β-cyclodextrin: Preparation, characterization and anticancer activity

In this study, the solid inclusion complex of oleanolic acid (OA) with methyl-beta-cyclodextrin (M-beta-CD) was prepared and characterized by nuclear magnetic resonance (NMR), X-ray diffraction (XRD), scanning electron microscope (SEM) and differential scanning calorimetry (DSC). The inclusion behaviors of OA/M-beta-CD complex were studied by fluorescence spectroscopy and the Job plot, which indicated a 1:1 inclusion mode between OA and M-beta-CD. The stability constant (Ks) of the complex was 1072.30 +/- 20 M-1 determined by spectral titration at 25 degrees C. Besides, the water solubility of OA was significantly increased to 8.2 mg/mL by inclusion complexation, compared to only ca. 0.012 mu g/mL of free OA. The in vitro cytotoxicity of the inclusion complex was noticeably better than that of native OA with the IC50 values of 8.89, 7.89 and 5.77 mu M on human cancer cell lines HepG2, HT29 and HCT116, respectively, by MTT assay. (C) 2016 Elsevier B.V. All rights reserved.