title: Targeting efficiency of galactosylated liposomes to hepatocytes in vivo: effect of lipid composition.
abstract: OBJECTIVE
  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 [3H]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]DSPC/Chol (60:40) liposomes, [3H]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.
authors.affiliation: Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Murao
authors.forename: Makiya
authors.initials: M
authors.lastname: Nishikawa
authors.forename: Chittima
authors.initials: C
authors.lastname: Managit
authors.forename: Joseph
authors.initials: J
authors.lastname: Wong
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Fumiyoshi
authors.initials: F
authors.lastname: Yamashita
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D008081:Liposomes / Q000008:administration & dosage / Q000378:metabolism; D008297:Male; D051379:Mice; D013862:Thiogalactosides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D008055:Lipids; D008081:Liposomes; D013862:Thiogalactosides