Title: Host-guest interaction of β-cyclodextrin with isomeric ursolic acid and oleanolic acid: physicochemical characterization and molecular modeling study
Authors: Yuan Huang1, , Peng Quan2, , Yongwei Wang3, Dongsheng Zhang4, Mingwan Zhang3, Rui Li3, Nan Jiang3
Institutions: 1Department of Pharmacy, Affiliated Wuxi Peoples Hospital, Nanjing Medical University, Wuxi, Jiangsu 214023, China; 2Department of Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, Liaoning 110016, China; 3School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu 211166, China; 4Department of Colorectal Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Abstract: Ursolic acid (UA) and oleanolic acid (OA) are insoluble drugs. The objective of this study was to encapsulate them into β-cyclodextrin (β-CD) and compare the solubility and intermolecular force of β-CD with the two isomeric triterpenic acids. The host-guest interaction was explored in liquid and solid state by ultraviolet-visible absorption, 1 H NMR, phase solubility analysis, and differential scanning calorimetry, X-ray powder diffractometry, and molecular modeling studies. Both experimental and theoretical studies revealed that β-CD formed 1: 1 water soluble inclusion complexes and the complexation process was naturally favorable. In addition, the overall results suggested that ring E with a carboxyl group of the drug was encapsulated into the hydrophobic CD nanocavity. Therefore, a clear different inclusion behavior was observed, and UA exhibited better affinity to β-CD compared with OA in various media due to little steric interference, which was beneficial to form stable inclusion complex with β-CD and increase its water solubility effectively.
Keywords: β-cyclodextrin, oleanolic acid, ursolic acid, host-guest interaction, molecular modeling