Objective: To develop and optimize the preparation protocols of fisetin liposomes, and to evaluate in vitro and in vivo the properties of liposomes obtained. Methods: Fisetin liposomes were prepared by film dispersion method. Taking the particle size as the index,fisetin liposomes with different total phospholipid and cholesterol, phospholipid cholesterol ratio and different drug lipid ratio were prepared to determine the optimal formulation through single factor analysis. The particle size, polydispersity coefficient and zeta potential of fisetin liposomes were measured by laser scattering particle size meter. The entrapment efficiency and drug loading were determined by ultrafiltration centrifugation.The stability, in vitro release in three media (pH 1.2 hydrochloric acid, double distilled water, pH 7.4 phosphate buffer), cytotoxicity and pharmacokinetics were also evaluated. Results:  The average particle size of fisetin liposomes prepared with the optimal formulation (fisetin 22.2 mg, phospholipid 133.3 mg, cholesterol 16.7 mg, sodium cholate 110 mg and isopropyl myristate 60 mg) was about (60.32±1.08)nm, the polydispersity coefficient was 0.198±0.011, the entrapment efficiency was (94.37±0.62)%, and the drug loading was (4.500±0.021)%.The results of transmission electron microscope showed that the liposomes were round and uniformly distributed in vitro; The solubility, in vitro release rate and relative bioavailability of fisetin could be improved in prepared liposomes; Fisetin liposomes showed good stability within 30 days. Furthermore, fisetin liposomes significantly inhibited the proliferation of human hepatoma HepG2 cells in a dose-dependent manner. Conclusion:  Fisetin liposomes can significantly improve the solubility and bioavailability of fisetin.

［Key words］fisetin；liposomes；in vitro and in vivo evaluation；insoluble drug；formulation development