The enhancement of the oral bioavailability of γ-tocotrienol in mice by γ-cyclodextrin inclusion

Cyclodextrin (CD) is widely used in the pharmaceutical and nutritional fields to form an inclusion complex with lipophilic compounds for the improvement of their aqueous solubility, stability and diffusibility under physiological conditions. In this study, we investigated the effect of the gamma-tocotrienol (gamma T3) inclusion complex with CD on its oral bioavailability. Five-week-old C57BL6 mice were fed a vitamin E-free diet for 28 days, followed by the oral administration of 2.79 mg of gamma T3-rich fraction (TRF) extracted from rice bran or the equivalent dose (14.5 mg) of a CD inclusion complex with TRF (TRF/CD). The levels of gamma T3 in sequentially collected plasma were determined by LC-MS/MS. The pharmacokinetic study revealed that the plasma concentrations of gamma T3 were increased and peaked at 6 or 3 h after the oral administration of TRF or TRF/CD, respectively (C-max values of 7.9 +/- 3.3 or 11.4 +/- 4.5 mu M, respectively). The area under the curve of plasma gamma T3 concentration also showed a 1.4-fold increase in the group administered with TRF/CD compared with the TRF-only group. Furthermore, the mice that had received the TRF/CD tended to reduce the endotoxin shock induced by injection with lethal amounts of Escherichia coli lipopolysaccharide, compared with the mice that had received TRF alone. Taken together, our results suggest that the CD inclusion improved gamma T3 bioavailability, resulting in the enhancement of gamma T3 physiological activity, which would be a useful approach for the nutrition delivery system. (C) 2011 Elsevier Inc. All rights reserved.