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.

Anti-Inflammatory and Physicochemical Characterization of the Croton rhamnifolioides Essential Oil Inclusion Complex in β-Cyclodextrin

“…Cyclodextrins (CD) represent one of the complexing agents most commonly used in the pharmaceutical industry due to their ability to improve the physical, chemical, and biological properties of bioactive molecules, especially those extracted from plants [ 58 ], although there is controversy regarding side effects in the renal system, in which orally administered β-CDs have been shown to induce limited toxicity. Jiang et al (2017) and Gould and Scott (2005) [ 59 , 60 ] evaluated the inclusion of triterpene acids in β-CD and obtained favorable results regarding the fit and binding to the β-CD cavity [ 59 , 60 ]. Their data demonstrated that the molecular interaction and complex formation between these compounds is given by the increased number of hydrogen bonds and hydrophobic interactions that promote conformational adjustments to take maximum advantage of the weak van der Waals forces in the hydrophobic cyclodextrin cavity [ 61 ].…”

Cyclodextrins, Natural Compounds, and Plant Bioactives—A Nutritional Perspective

“…During complexation, guest molecules and CD molecules come into contact with each other to unite and form a complex [ 50 ]. In most cases, one guest molecule forms a complex with one CD molecule, resulting in a 1:1 type of CD complex ( Figure 4 b) [ 4 , 26 , 51 ].…”

“…Therefore, water is almost necessary in the formation of complexes [ 50 ]. During the complexation process, negative values of free energy changes by the Gibbs equation have been shown for ursolic acid (UA) and oleanolic acid (OA) with βCD and γCD, respectively, indicating that complexation was a spontaneous process [ 24 , 26 ].…”

“…The host-guest interaction of OA and UA with βCD was studied by Huang et al [ 26 ]. They found that the kneading method resulted in products with higher drug loading, but limited improvement in solubility.…”

“…They found that the kneading method resulted in products with higher drug loading, but limited improvement in solubility. Therefore, the authors chose the stirring method because the stirred products showed better inclusion and were more easily obtained [ 26 ]. Furthermore, it has been shown that both the stability constant (K) and the complexation efficiency (CE) of UA were higher than those of OA.…”