Details

Autor(en) / Beteiligte

• Abuasal, Bilal S.
• Lucas, Courtney
• Peyton, Breanne
• Alayoubi, Alaadin
• Nazzal, Sami
• Sylvester, Paul W.
• Kaddoumi, Amal

Titel

Enhancement of Intestinal Permeability Utilizing Solid Lipid Nanoparticles Increases γ-Tocotrienol Oral Bioavailability

Ist Teil von

• Lipids, 2012-05, Vol.47 (5), p.461-469

Ort / Verlag

Berlin/Heidelberg: Springer-Verlag

Erscheinungsjahr

2012

Quelle

Access via Wiley Online Library

Beschreibungen/Notizen

• γ-Tocotrienol (γ-T3), a member of the vitamin E family, has been reported to possess an anticancer activity. γ-T3 is a lipophilic compound with low oral bioavailability. Previous studies showed that γ-T3 has low intestinal permeability. Thus, we have hypothesized that enhancing γ-T3 intestinal permeability will increase its oral bioavailability. Solid lipid nanoparticles (SLN) were tested as a model formulation to enhance γ-T3 permeability and bioavailability. γ-T3 intestinal permeability was compared using in situ rat intestinal perfusion, followed by in vivo relative oral bioavailability studies. In addition, in vitro cellular uptake of γ-T3 from SLN was compared to mixed micelles (MM) in a time and concentration-dependent studies. To elucidate the uptake mechanism(s) of γ-T3 from SLN and MM the contribution of NPC1L1 carrier-mediated uptake, endocytosis and passive permeability were investigated. In situ studies demonstrated SLN has tenfold higher permeability than MM. Subsequent in vivo studies showed γ-T3 relative oral bioavailability from SLN is threefold higher. Consistent with in situ results, in vitro concentration dependent studies revealed γ-T3 uptake from SLN was twofold higher than MM. In vitro mechanistic characterization showed that while endocytosis contributes to γ-T3 uptake from both formulations, the reduced contribution of NPC1L1 to the transport of γ-T3, and passive diffusion enhancement of γ-T3 are primary explanations for its enhanced uptake from SLN. In conclusion, SLN successfully enhanced γ-T3 oral bioavailability subsequent to enhanced passive permeability.