Nosiheptide is a drug with good anti-HBV activity but poor liver delivery due to its high liposolubility and low hepatocellular selectivity.In this study, high-density lipoprotein (HDL) was used as the drug carrier and a reconstituted HDL (rHDL)-nosiheptide complex was prepared via sonication and SDS dialysis to facilitate the liver targeting.The efficiency of the encapsulation of nosiheptide significantly increased to 90% when the nosiheptide and phosphatidylocholine (PC) ratio was 1∶50.The particle size was comparable to the naturally existing HDL when the PC and apoAI receptor ratio was 4∶1.The in vitro HBV inhibition assay indicated that 0.63μg/ml rHDL-nosiheptide complex could exert around 50% of inhibition on HBV.To reach the same level of inhibition in vitro, 40 times more nosiheptide liposome and 200 times more free nosiheptide were applied respectively.After injecting the rats for 30 min with this complex, 73% of the dose was found to be in the liver, and around 12% of the dose in the plasma.These results suggested that rHDL-nosiheptide complex had strong liver targeting property and it could be used for delivering drugs to treat liver diseases.