Quercetin nanocrystals stabilized by glycyrrhizic acid for liver targeted drug delivery：Impact of glycyrrhizic acid concentrations

The purpose of this study was to investigate the impact of glycyrrhizic acid (GL) concentrations on in vitro and in vivo behavior of quercetin (QT) nanocrystals stabilized by GL (QT-NCs/GL), with a particular focus on its influence on liver targeted drug delivery. QT-NCs/GL with similar particle size around 200 nm were successfully prepared by media milling technique using different concentrations of GL, which were 10%, 20% and 40% (w/w) of the QT. The impact of GL concentrations on morphology, crystalline state, solubility, drug release, as well as pharmacokinetic behavior and liver distribution of QT-NCs/GL following intravenous administration were investigated. An oval and short rod nanoparticles were observed for all QT-NCs/GL by scanning electron microscope. X-ray powder diffraction results showed all QT-NCs/GL remained in crystalline state, but a reduced crystallinity was found with increase of GL concentrations. All QT-NCs/GL exhibited significant solubility increase and drug release improvement of QT as compared to raw QT. There was no significant difference in the plasma concentration-time curve and pharmacokinetic parameters of QT after intravenous of all QT-NCs/GL, except that the AUC0∼t of QT-NCs/GL-10% was significantly higher than that of QT-NCs/GL-20%. All QT-NCs/GL exhibited rapidly distribution of QT to liver with the maximum QT concentration more than 750 μg/g at 5 min after intravenous administration, and the AUC0∼t of QT for three formulations in liver were significant difference with the following order: QT-NCs/GL-40% > QT-NCs/GL-20% > QT-NCs/GL-10%. It could be concluded that different GL concentrations exhibited significant influence on liver targeted delivery of QT-NCs/GL, and more GL used in QT-NCs/GL may contribute more liver distribution of QT.