Quercetin LipoMicel—A Novel Delivery System to Enhance Bioavailability of Quercetin

Abstract

BACKGROUND: Quercetin, a flavonoid found in plant-based foods, has a range of biological activities that may be beneficial for human health. The pharmacokinetic profile of quercetin remains, however, a limiting factor for its use as a nutritional supplement. Quercetin LipoMicel ® -a novel delivery system encapsulating quercetin into a liquid micelle matrix-has been designed to address the low bioavailability issue associated with non-conjugated forms by improving the absorption of quercetin. OBJECTIVE:The purpose of this study was to evaluate the solubility and gastrointestinal absorption of quercetin in a novel Quercetin LipoMicel delivery system in healthy adult volunteers by comparing it with free quercetin and another commercial quercetin product. Several pharmacokinetic parameters were compared between these three formulations. METHODS:Twelve healthy adult male and female volunteers aged between 21 and 65, with BMIs under 30, participated in a non-blinded, crossover bioavailability study conducted with three quercetin products. Each treatment contained a total dose of 500 mg quercetin. Capillary whole blood samples from participants were collected serially at intervals from 0-24 hours. Quercetin concentrations were detected and measured by ultra-performance liquid chromatography (UHPLC) coupled to a Thermo QExactive Orbitrap Mass Spectrometer. Solubility of quercetin in water and simulated gastrointestinal media was determined by UHPLC. RESULTS:Oral absorption of quercetin was significantly enhanced with the LipoMicel delivery system compared to free quercetin. Improvements in in vitro gastric stability and intestinal solubility were observed with LipoMicel, leading to significantly higher blood concentration and enhanced duration of a stable concentration of quercetin in the body. Compared to free quercetin, 8-and 9-fold increases in AUC and Cmax were attained with the LipoMicel delivery system, and 10-fold higher quercetin plasma concentrations detected at 12 hours after administration. CONCLUSIONS:Quercetin LipoMicel represents an efficient delivery system for augmenting the bioavailability of quercetin in vivo. Significantly higher blood concentrations and a sustained release of quercetin over the study period was achieved following the administration of quercetin via the LipoMicel technology. Optimization in the in vivo bioavailability of quercetin may promote its salutary effects.

Optimization and Characterization of <i>Cuscuta reflexa </i>Extract Loaded Phytosomes by the Box-Behnken Design to Improve the Oral Bioavailability

“…In other words, phytosome is an entirely new, patentpending method of incorporating hydrophilic phytoconstituents or standardized plant extracts into the phospholipids to produce lipid-compatible molecules with greater bioavailability than conventional herbal extracts thus they have a greater potential to penetrate the lipoidal biomembrane and subsequently enter the systemic circulation 19) .…”

Research Progress on Quercetin's Biological Activity and Structural Modification Based on Its Antitumor Effects

“…Poor water solubility (0.01 mg/m) and low absorption and oral bioavailability of quercetin may be attributed to premature degradation in the stomach and low stability of the glycosides (which depended on temperature, pH, metal ions and the presence of glutathione). [99,101] The absorption of quercetin could be improved by ingesting with meals, as the greater surface area promoted its dissolution in the intestinal lumen thereby increasing bioavailability. [102] Ferry et al investigated the pharmacokinetic properties of intravenous quercetin at dose levels of 60-2000 mg/m 2 in cancer patients.…”

“…Absorption of quercetin is highly individualized, which may be caused by variations in metabolic enzymes and transporters in the intestine and liver. Poor water solubility (0.01 mg/m) and low absorption and oral bioavailability of quercetin may be attributed to premature degradation in the stomach and low stability of the glycosides (which depended on temperature, pH, metal ions and the presence of glutathione) [99,101] . The absorption of quercetin could be improved by ingesting with meals, as the greater surface area promoted its dissolution in the intestinal lumen thereby increasing bioavailability [102] …”

“…Metabolites of quercetin resulting from methylation, sulfonation, and glucuronide splicing circulated in the blood and were subsequently excreted in the bile and urine [98] . In healthy participants, the presence of a secondary peak in the blood concentration versus time curve of quercetin suggested an enterohepatic circulation for quercetin absorption [99] . Quercetin and its metabolites accumulated most in the lungs, liver and kidneys and could pass the blood‐brain barrier [100] .…”

“…[98] In healthy participants, the presence of a secondary peak in the blood concentration versus time curve of quercetin suggested an enterohepatic circulation for quercetin absorption. [99] Quercetin and its metabolites accumulated most in the lungs, liver and kidneys and could pass the blood-brain barrier. [100] As a main metabolite of quercetin, quercetin-3-O-β-D-glucuronide can be transported to target tissues via plasma to exert the corresponding biological activity.…”