Targeting efficiency of galactosylated liposomes to hepatocytes in vivo:: Effect of lipid composition

Purpose. To investigate the effects of the lipid composition of galactosylated liposomes on their targeted delivery to hepatocytes. Methods. Several types of liposomes with a particle size of about 90 nm were prepared using distearoyl- L- phosphatidylcholine (DSPC), cholesterol (Chol) and cholesten- 5- yloxy- N-( 4-(( 1- imino- 2- D-thiogalactosylethyl) amino) butyl) formamide (Gal- C4- Chol), and labeled with [ 3 H] cholesterol hexadecyl ether. Their tissue disposition was investigated in mice following intravenous injection. The binding and internalization characteristics were also studied in HepG2 cells. Results. Compared with [H-3]DSPC/Chol (60: 40) liposomes, [H-3] DSPC/ Chol/ Gal- C4- Chol (60: 35: 5) liposomes exhibit extensive hepatic uptake. Separation of the liver cells showed that galactosylated liposomes are preferentially taken up by hepatocytes, whereas those lacking Gal- C4- Chol distribute equally to hepatocytes and nonparenchymal cells (NPC). Increasing the molar ratio of DSPC to 90% resulted in enhanced NPC uptake of both liposomes, suggesting their uptake via a mechanism other than asialoglycoprotein receptors. DSPC/ Chol/ Gal- C4- Chol (60: 35: 5) and DSPC/ Chol/ Gal- C4- Chol (90: 5: 5) liposomes exhibited similar binding to the surface of HepG2 cells, but the former were taken up faster by the cells. Conclusions. The recognition of galactosylated liposomes by the asialoglycoprotein receptors is dependent on the lipid composition. Cholesterol- rich galactosylated liposomes, exhibiting less non- specific interaction and greater receptor- mediated uptake, are better for targeting drugs to hepatocytes in vivo.