Hepatitis B virus preS1-derived lipopeptide functionalized liposomes for targeting of hepatic cells.

To enhance the liver-specific delivery, HBVpreS/2-48(myr) (HBVP), a synthetic HBVpreS-derived lipopeptide endowed with compelling liver tropism, was conjugated to PEGylated liposomes (HBVP-Lip) for hepatic cell-specific delivery. Compared with the non-targeted liposomes, a significantly higher amount of HBVP-Lip were taken up by the primary mice hepatocytes through a receptor-mediated endocytosis mechanism. The endocytosis inhibition assay demonstrated that the endocytosis of HBVP-Lip was mediated mainly by caveolin and clathrin. After systemic administration in mice, HBVP-Lip could be specifically internalized into hepatocytes efficaciously. Furthermore, the hepatoprotective effects of HBVP-Lip loaded with silybin (SLB) on carbon tetrachloride induced acute liver damage were remarkably stronger than the SLB solution and SLB loaded non-targeted liposomes. Preliminary safety results suggested that no acute systemic toxicity or immunotoxicity was observed after intravenous administration with HBVP-Lip. These results indicated that the HBVP-Lip could deliver the payloads to the hepatocytes with high specificity in vitro and in vivo, and raise new possibilities for liver-specific drug delivery systems, gene delivery systems, and bio-imaging systems.