机构：[1]Faculty of Life Science and Technology, Kunming University of Science and Technology, 650500, Kunming, China[2]Jiangsu Xinchen Pharmaceutical Co., LTD, 222047, Lianyungang, China[3]Faculty of Medicine, Kunming University of Science and Technology, Kunming, 650500, China[4]Research Centre for Pharmaceutical Care and Quality Management, First People’s Hospital of Yunnan Province, Kunming, 650500, China云南省第一人民医院[5]Current address: Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.
Ursolic acid (UA) is a pentacyclic triterpenoid of naturally abundance with a broad spectrum of important biological activities and low toxicity. However, potential applications in pharmaceutical industry are severely hampered by its poor water solubility, which leads to low bioavailability. Herein, we harness the unique and superior inclusion capability of a series of amino-appended beta-cyclodextrins (ACDs) to prepare solid inclusion complexes of UA/ACDs. These inclusion complexes were characterized in their solid state by scanning electron microscope (SEM), differential scanning calorimetry (DSC), thermogravimetric (TG) and powder X-ray diffraction (XRD) analyses. Furthermore, their supramolecular binding behavior in aqueous solution was investigated by one-dimensional (1D)- and two-dimensional (2D)-nuclear magnetic resonance (NMR) spectroscopic experiments and NMR-based phase solubility analysis. Binding stability constants (Ks) were determined (1799, 1410, 889 and 993 L mol(-1) for UA/a0, UA/a1, UA/a2 and UA/a3, respectively), and dynamic bimodal inclusion modes with a 1:1 inclusion stoichiometry for UA/ ACDs systems were proposed. Water solubility of UA is dramatically promoted by more than 200-fold after formation of inclusion complexes. In vitro cytotoxicity of UA achieves significant elevation against human cancer cell lines HepG2, HT-29 and HCT116 by inclusion complexation from MIT assay, while these inclusion complexes show no cytotoxicity against human normal cell line LO2, which confirms their safety. These results would benefit to the further development of liquid formulation of UA for pharmaceutical uses. (C) 2019 Elsevier B.V. All rights reserved.
基金：
This work was financial supported by Yunnan Applied Basic
Research Projects (Nos. 2018FB018 & 2018FA047) and the National
Natural Science Foundation of China (NNFSC) (Nos. 21961017 &
81560601).
第一作者机构：[1]Faculty of Life Science and Technology, Kunming University of Science and Technology, 650500, Kunming, China
共同第一作者：
通讯作者：
通讯机构：[1]Faculty of Life Science and Technology, Kunming University of Science and Technology, 650500, Kunming, China[*1]Faculty of Life Science and Technology, Kunming University of Science and Technology, 650500, Kunming, China.
推荐引用方式(GB/T 7714)：
Song Shuang,Gao Kai,Niu Raomei,et al.Binding behavior, water solubility and in vitro cytotoxicity of inclusion complexes between ursolic acid and amino-appended beta-cyclodextrins[J].JOURNAL OF MOLECULAR LIQUIDS.2019,296:doi:10.1016/j.molliq.2019.111993.
APA：
Song, Shuang,Gao, Kai,Niu, Raomei,Yi, Wenlong,Zhang, Jihong...&Liao, Xiali.(2019).Binding behavior, water solubility and in vitro cytotoxicity of inclusion complexes between ursolic acid and amino-appended beta-cyclodextrins.JOURNAL OF MOLECULAR LIQUIDS,296,
MLA：
Song, Shuang,et al."Binding behavior, water solubility and in vitro cytotoxicity of inclusion complexes between ursolic acid and amino-appended beta-cyclodextrins".JOURNAL OF MOLECULAR LIQUIDS 296.(2019)
化学