Binding behavior, water solubility and in vitro cytotoxicity of inclusion complexes between ursolic acid and amino-appended beta-cyclodextrins

Shuang Song, Kai Gao, Raomei Niu, Wenlong Yi, Jihong Zhang, Chuanzhu Gao, Bo Yang, Xiali Liao*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number111993
Number of pages9
JournalJournal of Molecular Liquids
Volume296
DOIs
Publication statusPublished - 15-Dec-2019

Keywords

  • Ursolic acid
  • Amino-appended beta-cyclodextrin (ACD)
  • Inclusion complex
  • Binding behavior
  • Water solubility
  • In vitro cytotoxicity
  • OLEANOLIC ACID
  • PHYSICOCHEMICAL PROPERTIES
  • SUPRAMOLECULAR CATALYSIS
  • SELECTIVE BINDING
  • ANTIBACTERIAL
  • THERAPEUTICS
  • MOLECULES
  • ACDS

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