Solid inclusion complexes of oleanolic acid with amino-appended β-cyclodextrins (ACDs): Preparation, characterization, water solubility and anticancer activity.
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.
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Yufeng
Y
Ren
Faculty of Medicine, Kunming University of Science and Technology, Kunming 650500, China.
Ying
Y
Liu
Faculty of Medicine, Kunming University of Science and Technology, Kunming 650500, China.
Zhikuan
Z
Yang
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Raomei
R
Niu
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Kai
K
Gao
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China.
Bo
B
Yang
Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming 650500, China. Electronic address: xlliao@yahoo.com.
Xiali
X
Liao
Faculty of Medicine, Kunming University of Science and Technology, Kunming 650500, China; Research Centre for Pharmaceutical Care and Quality Management, First People's Hospital of Yunnan Province, Kunming 650500, China. Electronic address: zhangjihong2000@126.com.
Jihong
J
Zhang
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D045325:HCT116 Cells; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D009828:Oleanolic Acid / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
D000970:Antineoplastic Agents; D047392:beta-Cyclodextrins; D014867:Water; D009828:Oleanolic Acid
Amino-appended β-cyclodextrin; Anticancer activity; Binding behavior; Inclusion complex; Oleanolic acid; Water solubility