Stability, Antioxidant Activity and Intestinal Permeation of Oleuropein Inclusion Complexes with Beta-Cyclodextrin and Hydroxypropyl-Beta-Cyclodextrin.

ABSTRACT

Compared to beta-cyclodextrins (beta-CD), hydroxypropyl-beta-cyclodextrins (HP-beta-CD) are a more popular material used to prepare inclusion complexes due to their superior solubility and intestinal absorption. In this study, oleuropein (OL) inclusion complexes with beta-CD (beta-CDOL) and HP-beta-CD (HP-beta-CDOL) were prepared and the formation of inclusion complexes was validated by IR, PXRD, and DSC. A phase solubility test showed that the lgK (25 °C) and binding energy of beta-CDOL and HP-beta-CDOL was 2.32 versus 1.98, and −6.1 versus −24.66 KJ/mol, respectively. Beta-CDOL exhibited a more powerful effect than HP-beta-CDOL in protecting OL from degradation upon exposure to light, high temperature and high humidity. Molecular docking, peak intensity of carbonyls in IR, and ferric reducing power revealed that beta-CDOL formed more hydrogen bonds with the unstable groups of OL. Both inclusion complexes significantly enhanced the solubility, intestinal permeation and antioxidant activity of OL (p < 0.05). Though HP-beta-CDOL had higher solubility and intestinal absorption over beta-CDOL, the difference was not significant (p > 0.05). The study implies that lower binding energy is not always associated with the higher stability of a complex. Beta-CD can protect a multiple-hydroxyl compound more efficiently than HP-beta-CD with the intestinal permeation comparable to HP-beta-CD complex.