Enhanced bioavailability and pharmacokinetics of a novel hybrid-hydrogel formulation of fisetin orally administered in healthy individuals: a randomised double-blinded comparative crossover study

Abstract

Fisetin, a polyphenol found in several fruits and vegetables, has shown potential health benefits in many pre-clinical studies for neuroprotection, cardioprotection, chemoprevention, diabetes, inflammation and oxidative stress. However, the clinical effectiveness of fisetin may be limited by its poor bioavailability when ingested. Using a novel green technology of Hybrid-FENUMAT™, a food-grade fisetin formulation (FF-20) was developed through encapsulation of fisetin micelles into fenugreek galactomannan (FG) hydrogel scaffold to improve its physical characteristics and bioavailability. This is the first human pharmacokinetic study of fisetin following a single-dose, comparative, double-blinded, cross-over protocol, supplementing with FF-20 and unformulated fisetin (UF). Fifteen healthy volunteers were given a single dose of 1000 mg UF or 1000 mg FF-20 (delivering 192 mg fisetin) with a 10-d washout period between each dose. Blood samples were taken at 0⋅5, 1, 2, 3, 5, 8 and 12 h after both days of supplementation to quantify fisetin and geraldol, an active metabolite. The plasma concentration of fisetin when individuals consumed FF-20 was 26⋅9-fold greater than UF as determined by the area under the curve over 12 h [AUC0–12 h (FF-20) = 341⋅4 v. AUC0–12 h (UF) = 12⋅67]. The maximum plasma concentration (Cmax) was also more than twenty-three times higher when supplemented with FF-20 (238⋅2 ng/ml) compared to UF (9⋅97 ng/ml). The encapsulation also reduced the amount of conversion of fisetin to geraldol. No adverse events were reported during the study. Therefore, the encapsulation of fisetin into FG dietary fibre hydrogel scaffold could improve its delivery and bioavailability in human subjects.

Keywords

• Bioavailability
• Fenugreek galactomannans
• Fenumat
• Fisetin
• Flavonoids
• Pharmacokinetics