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

Abstract

Despite the vast array of health beneficial pharmacological effects, the bioavailability of the dietary flavonoid quercetin was found to be poor due to insolubility, incompatibility, and rapid biotransformation. Herein, we investigated the solubility, morphology, particle size, stability, in vitro release, and human pharmacokinetics of a hybrid-hydrogel formulation of quercetin (FQ-35) using fenugreek galactomannans as the hydrogel scaffold. Physicochemical characterization revealed that the crystalline quercetin was well encapsulated in the hydrogel matrix to form translucent microgel particles of FQ-35 with enhanced solubility (96-fold). The mean particle size was found to be 183.6 ± 42.7 nm with a zeta potential of 35.1 ± 3.8 mV. Pharmacokinetic investigation on healthy volunteers (N = 16) employing tandem mass spectrometric (ultra-performance liquid chromatography-electrospray tandem mass spectrometry) measurements of the concentration of free (unconjugated) and conjugated quercetin metabolites revealed an 18.6-fold improvement in free (unconjugated) quercetin bioavailability and 62-fold improvement in total quercetin (sum of free and conjugated) bioavailability, compared to the unformulated quercetin extracted from Sophora japonica. In summary, the natural self-emulsifying reversible hybrid-hydrogel delivery system was found to offer significant solubility, stability, and bioavailability of quercetin upon single-dose oral administration.