Fabrication and In Vitro/Vivo Evaluation of Drug Nanocrystals Self-Stabilized Pickering Emulsion for Oral Delivery of Quercetin

Abstract

The aim of this study was to develop a new drug nanocrystals self-stabilized Pickering emulsion (NSSPE) for improving oral bioavailability of quercetin (QT). Quercetin nanocrystal (QT–NC) was fabricated by high pressure homogenization method, and QT–NSSPE was then prepared by ultrasound method with QT–NC as solid particle stabilizer and optimized by Box-Behnken design. The optimized QT–NSSPE was characterized by fluorescence microscope (FM), scanning electron micrograph (SEM), X-ray diffraction (XRD), and differential scanning calorimetry (DSC). The stability, in vitro release, and in vivo oral bioavailability of QT–NSSPE were also investigated. Results showed that the droplets of QT–NSSPE with the size of 10.29 ± 0.44 μm exhibited a core-shell structure consisting of a core of oil and a shell of QT–NC. QT–NSSPE has shown a great stability in droplets shape, size, creaming index, zeta potential, and QT content during 30 days storage at 4, 25, and 40 °C. In vitro release studies showed that QT–NSSPE performed a better dissolution behavior (65.88% within 24 h) as compared to QT–NC (50.71%) and QT coarse powder (20.15%). After oral administration, the AUC0–t of QT–NSSPE was increased by 2.76-times and 1.38 times compared with QT coarse powder and QT–NC. It could be concluded that NSSPE is a promising oral delivery system for improving the oral bioavailability of QT.

Preparation and Characterization of a Novel Natural Quercetin Self-Stabilizing Pickering Emulsion

“…As shown in Figure 4 A, the XRD spectra at 10–30° showed a series of sharp peaks, indicating the crystalline nature of quercetin. The typic peaks of the native quercetin are mainly at 2 of 6.3–7.3°, 10.8°, 12.5°, 13.6–14.3°, 15.7–18.0°, 24.4°, and 27.3°, which represented the crystalline part of quercetin [ 25 ]. Compared with the native quercetin, the quercetin particles obtained by antisolvent precipitation have the same diffraction peaks of 12.5°, 13.6–14.3°, 24.4°, and 27.3°, but have almost no diffraction peaks of 6.3–7.3°, 10.9°, and 15.7–18.0°.…”

“…Zhang et al found that puerarin nanocrystals obtained using high pressure homogenization can stabilize oil-in-water Pickering emulsions [ 24 ]. Wang et al reported that quercetin nanocrystals obtained by high pressure homogenization could be used for the stabilization of oil-in-water Pickering emulsions [ 25 ]. Silybin nanocrystals with 340 nm were also fabricated using high-pressure homogenization methods under >80 MPa [ 26 ].…”

“…The inherent crystalline nature of flavonoids makes them excellent candidates for stabilizing Pickering emulsions (particle-stabilized emulsions) if they have proper surface wettability. Although some recent studies have successively found that flavonoids can stabilize Pickering emulsions, most of these flavonoids are used in their native state or are high-pressure processed [ 17 , 18 , 25 ]. The effect of antisolvent precipitation on the performance of flavonoids (e.g., quercetin) in Pickering emulsion stabilization have been less frequently studied.…”

Quercetin nanoformulations: recent advancements and therapeutic applications

“…In another study, anti-solvent crystallisation method was used to develop quercetin nanocrystals by Li et al The prepared nanocrystals showed 24.6 ± 1.9 mV zeta potential, and enhanced bioavailability of quercetin [53]. Wang et al formulated quercetin nanocrystals using HPH method, and the developed quercetin nanocrystals showed 20.15% drug release, enhanced stability and therapeutic effect of quercetin [54].…”

“…A study was conducted on rats by Wang et al with a 50 mg kg −1 dose of quercetin encapsulated nanocrystal formulation. The result reported a higher plasma concentration of quercetin and enhanced bioavailability as compared to quercetin coarse powder suspension [54]. Ly et al evaluated the anti-cancer potential of quercetin-NPs by performing trials on female BALB/c nude mice.…”