Two-birds-one-stone, microfluidic producing DES/W microemulsions to solubilize quercetin and penetrate intestinal mucosa for enhanced oral bioavailability

Quercetin has antioxidant, anti-inflammatory, antibacterial, and anticancer effects. However, its therapeutic efficacy is limited by poor water solubility, low oral absorption, and limited bioavailability. In this study, a novel deep eutectic solvent (DES) in water (DES/W) microemulsion system was developed, wherein the DES was composed of DL-menthol and capric acid at a molar ratio of 7:3, to simultaneously accomplish enhanced quercetin solubilization and promoted mucosal permeation, both of which ensuring an adequate oral bioavailability and sufficient therapeutic effectiveness. Optimized DESs were used with microfluidic technology to create uniform quercetin-loaded DES/W microemulsions under the optimal formulation conditions: Tween 20 as the surfactant, a surfactant concentration of 1.37%, a continuous phase flow rate of 30.98 mL/h, and a dispersed phase flow rate of 3.15 mL/h. The results showed that the obtained microemulsions increased quercetin solubility, retention time in the intestines, and mucosal absorption, improving drug absorption and bioavailability. Pharmacokinetic studies showed that compared with free quercetin, the area under the plasma concentration–time curve (AUC 0～t ) and maximum plasma concentration (C max ) of the microemulsion formulation were significantly increased, with AUC 0～t being 5.54-fold higher than that of free quercetin. Notably, the use of microfluidic technology in preparing these microemulsions considerably reduces the need for surfactants, thus enhancing the biosafety of DES-based microemulsions. Overall, the DES/W microemulsions prepared by microfluidics could effectively addresses the challenges associated with poor absorption and low bioavailability of insoluble drugs with highly monodisperse and uniform formulations.