Glycyrrhetinic acid-modified silybin B liposomes for non-alcoholic fatty liver disease therapy via increasing hepatic delivery efficiency

Silybin is a clinically validated adjunct for liver disorders, yet poor absorption and rapid metabolism curtail its wider therapeutic use. Exploiting the distinctive hepatic distribution of glycyrrhetinic acid (GA) receptors, we augmented silybin B (SilB, an isomer of silybin) delivery by encapsulating it within GA-modified liposomes. We constructed a response-surface model to optimize liposome fabrication, identifying the optimal recipe: 5.89:1 lecithin/cholesterol, 100:2.13 lecithin/DSPE-PEG2000, and 12:5.05 lecithin/SilB. DSPE-PEG2000-GA was generated through amidation and substituted for DSPE-PEG2000 to yield GA-modified SilB liposomes (GSL). GSL exhibited 49.34 ± 0.25% encapsulation efficiency, 9.13 ± 0.04% drug loading, 148.881 ± 4.786 nm diameter, 0.269 ± 0.024 polydispersity index, and −23.433 ± 0.775 mV zeta potential. GSL remained stable for 7 days and sustained drug release for 24 h in PBS. GA-modified liposomes displayed accelerated HepG2 uptake and heightened murine hepatic retention, underpinning its superior therapeutic performance. GSL engaged non-alcoholic fatty liver disease on multiple aspects, suppressing lipid accretion, inflammation, and insulin resistance, and significantly surpassed free SilB in therapeutic magnitude. Download: Download high-res image (305KB) Download: Download full-size image