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

• Solid inclusion complex of oleanolic acid (OA) with methyl-β-CD (M-β-CD) was prepared and was characterized by NMR, XRD, SEM and DSC analyses.
• The inclusion stoichiometry was 1:1 and the stability constant (Ks) was 1072.30 ± 20 M−1 for the inclusion complex.
• Water solubility of OA was significantly increased by inclusion complexation with M-β-CD.
• In vitro cytotoxity of OA on human cancer cell lines HepG2, HT29 and HCT116 was markedly promoted.

In this study, the solid inclusion complex of oleanolic acid (OA) with methyl-β-cyclodextrin (M-β-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-β-CD complex were studied by fluorescence spectroscopy and the Job plot, which indicated a 1:1 inclusion mode between OA and M-β-CD. The stability constant (Ks) of the complex was 1072.30 ± 20 M−1 determined by spectral titration at 25 °C. Besides, the water solubility of OA was significantly increased to 8.2 mg/mL by inclusion complexation, compared to only ca. 0.012 μg/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 μM on human cancer cell lines HepG2, HT29 and HCT116, respectively, by MTT assay.

Oleanolic acid (OA) is of natural abundance and possesses impressive biological activities. However, its applications were severely hindered by its poor water solubility and low bioavailability. Here the established OA/methyl-β-cyclodextrin (M-β-CD) solid inclusion complex exhibited striking promotion of water solubility and significant enhancement of in vitro cytotoxicity against human cancer cell lines.Figure optionsDownload as PowerPoint slide