This study aimed to create a glycyrrhetinic acid (GA)-mediated, multi-component, self-assembled nano-drug delivery system co-loaded with syringopicroside (S) and hydroxytyrosol (H) obtained from Syringa Linn by synthesizing a GA-polyethylene glycol-poly (lactic acid-co-glycolic acid) (GPP) nanoparticle delivery carrier to actively target the liver. The nanoparticles were optimized using the central composite design. Nanoparticle characterization, cytotoxicity, pharmacodynamics, and tissue distribution study were performed. The optimized SH-GPP nanoparticle was a white solid powder, which was safe and non-toxic. The particle size and Zeta potential of the nanoparticles were 101.5 ± 3.18 nm and -23.3 ± 0.82 mV, respectively. The polydispersity index value (PDI) was 0.190 ± 0.005; the particle size distribution was comparatively uniform. The average total encapsulation efficiency of the optimized SH-GPP nanoparticle was 50.26% ± 1.29%, and drug loading was 15.47% ± 0.39%. After S and H were arranged into nanoparticles, the proliferation inhibition of HepG2.2.15 cells was improved, and the aim of drug-loaded synergism between GPP and SH was achieved. The GA-mediated nanoparticles were better targeted, were retained longer in vivo, and had higher concentrations in the liver than the unmodified nanoparticles. These nanoparticles have the potential to be a new effective anti-hepatitis B treatment and have great research potential in clinical treatment.
Keywords: PEG-PLGA; glycyrrhetinic acid; liver disease; nano-drug delivery system; nanoparticle delivery carrier.