Solid inclusion complexes of oleanolic acid with amino-appended β-cyclodextrins (ACDs): Preparation, characterization, water solubility and anticancer activity

• Solid inclusion complexes of oleanolic acid (OA) with well-designed amino-appended β-cyclodextrins (ACDs) were prepared.
• Inclusion complexes were intensively characterized by NMR, SEM, XRD, TG, DSC and Zeta potential measurement, etc.
• A 1:2 inclusion mode was suggested based on 1H NMR and ROESY analyses.
• Water solubility of OA was dramatically promoted by complexation with ACDs compared to that of native OA.
• In vitro cytotoxicity of inclusion complexes on human cancer cell lines HepG2, HT29 and HCT116 was significantly enhanced.

Oleanolic acid (OA) is a pentacyclic triterpenoid acid of natural abundance in plants which possesses important biological activities. However, its medicinal applications were severely impeded by the poor water solubility and resultant low bioavailability and potency. In this work, studies on solid inclusion complexes of OA with a series of amino-appended β-cyclodextrins (ACDs) were conducted in order to address this issue. These complexes were prepared by suspension method and were well characterized by NMR, SEM, XRD, TG, DSC and Zeta potential measurement. The 2:1 inclusion mode of ACDs/OA complexes was elucidated by elaborate 2D NMR (ROESY). Besides, water solubility of OA was dramatically promoted by inclusion complexation with ACDs. Moreover, in vitro anticancer activities of OA against human cancer cell lines HepG2, HT29 and HCT116 were significantly enhanced after formation of inclusion complexes, while the apoptotic response results indicated their induction of apoptosis of cancer cells. This could provide a novel approach to development of novel pharmaceutical formulations of OA.

Figure optionsDownload as PowerPoint slide