Hepatic targeting of glycyrrhetinic acid viananomicelles based on stearic acid-modifiedfenugreek gum///ABSTRACTThis study aimed to increase the solubility of glycyrrhetinic acid (GA) in water and enhance its liver-targeting ability using self-assembling nanomicelles (NMs) based on stearic acid-modified fenugreek gum(FG-C18). The GA/FG-C18 NMs were prepared by an ultrasonication dispersion method. The nanomicelleswere spherical particles with a particle size of 198.61 ± 1.58 nm and a zeta potential of30.12 ± 0.28 mV. The drug loading and encapsulation efficiency were 13.34 ± 0.24% and 80.07 ± 1.44%,respectively. The results of differential scanning calorimetry (DSC) and X-ray powder diffraction (XRD)indicated that GA was successfully encapsulated into the nanomicelles in a molecularly dispersed state.An in vitro release test showed that GA/FG-C18 NMs possessed a slow drug release profile in PBS (pH7.4) over 200 h. The cytotoxicity assay indicated that GA/FG-C18 NMs showed much higher inhibitoryefficacy in HepG2 cells than in MCF-7 cells. Tissue section studies indicated that the accumulation ofDiR-loaded FG-C18 nanomicelles in the liver of mice was higher than that of the DiR solution, and thefluorescence intensity decreased over time. GA/FG-C18 NMs showed a larger area under the curve(AUC) and mean residence time (MRT) compared with free GA after intravenous administration in mice.The in vivo studies showed that GA mainly accumulated in the liver after encapsulation by FG-C18 NMs,and the drug concentration was higher than that of free GA. These results suggested that FG-C18 NMscould serve as a potential drug delivery system for targeting GA to liver tissue.