Host-guest interaction of β-cyclodextrin with isomeric ursolic acid and oleanolic acid: physicochemical characterization and molecular modeling study

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

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (21303086), the Natural Science Foundation of Jiangsu Province (BK20130884), and the Research Fund for Doctoral Program of Higher Education (20123234120012). We thank the High Performance Computing Center at Shanghai.

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