title: The enhancement of the oral bioavailability of γ-tocotrienol in mice by γ-cyclodextrin inclusion.
abstract: 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 γ-tocotrienol (γT3) 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 γT3-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 γT3 in sequentially collected plasma were determined by LC-MS/MS. The pharmacokinetic study revealed that the plasma concentrations of γT3 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 μM, respectively). The area under the curve of plasma γT3 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 γT3 bioavailability, resulting in the enhancement of γT3 physiological activity, which would be a useful approach for the nutrition delivery system.
authors.affiliation: Laboratory of Biochemistry and Global Center of Excellence Program, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, Shizuoka 422-8526, Japan. miyoshin@u-shizuoka-ken.ac.jp
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Miyoshi
authors.forename: Yohei
authors.initials: Y
authors.lastname: Wakao
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomono
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tatemichi
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohshima
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002839:Chromans / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000378:metabolism; D008297:Male; D051379:Mice; D014810:Vitamin E / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D047408:gamma-Cyclodextrins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D002839:Chromans; D008070:Lipopolysaccharides; D047408:gamma-Cyclodextrins; D014810:Vitamin E; C013649:plastochromanol 8