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.

Fisetin, a dietary flavonoid, increases the sensitivity of chemoresistant head and neck carcinoma cells to cisplatin possibly through HSP90AA1/IL‐17 pathway

“…The patient's compliance would be relatively high because it can be obtained in the daily diet. Nevertheless, its clinical application research is limited due to its poor water solubility, poor oral bioavailability, rapid metabolism, and degradation in the gastrointestinal tract after oral administration (Krishnakumar et al, 2022). Based on the poor bioavailability of fisetin after oral administration, frequent and high doses are expected to be more effective (Krishnakumar et al, 2022).…”

“…Nevertheless, its clinical application research is limited due to its poor water solubility, poor oral bioavailability, rapid metabolism, and degradation in the gastrointestinal tract after oral administration (Krishnakumar et al, 2022). Based on the poor bioavailability of fisetin after oral administration, frequent and high doses are expected to be more effective (Krishnakumar et al, 2022). Therefore, in the animal experiments, we used the intraperitoneal injection method instead of oral administration.…”

Enhanced Bioavailability and Pharmacokinetics of a Natural Self-Emulsifying Reversible Hybrid-Hydrogel System of Quercetin: A Randomized Double-Blinded Comparative Crossover Study

“…Hybrid-hydrogels have been identified as a promising approach for oral drug delivery systems since they can enhance the in vivo stability and release properties of drugs . High molecular weight, extensive hydration to stable softgel, mucoadhesive character, high emulsifying capacity, and amphiphilic nature to bind both oil and water make fenugreek galactomannan (FenuMAT) to behave like a cross-linked polymer for drug delivery. ,, The microstructure of FG allows the encapsulation of hydrophobic molecules in its conformationally directed hydrophobic pockets created in the swollen network. This is clear from the observed high encapsulation efficiency (>95%) of quercetin in FQ-35.…”

“…Such release properties of fenugreek galactomannan-based hydrogel formulations have already been reported for similar flavonoids, resveratrol, and fistein recently. 28 , 41 The hydrogel-quercetin system using β-lactoglobulin and sodium alginate has also been shown to exhibit good encapsulation efficacy and sustained release. 39 Similarly, Liu et al have reported quercetin encapsulation on whey protein microgels coated with lotus root amylopectin and its enhanced in vivo bioavailability, indicating the viability of hydrogel delivery systems.…”

Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress

“…Fisetin is considered a drug and nutritive supplement and is also recognized as a medical food, which stimulates more preclinical studies that could be translate into human clinical trials. One current clinical trial revealed important enhancement in anti-inflammatory markers when fisetin was injected into subjects with colorectal cancer [ 31 , 32 ]. A clinical study in stroke patients showed that fisetin was able to improve the treatment results, particularly in people with delayed onset-of-treatment [ 33 ].…”