title: Novel Galactosylated Poly(ethylene glycol)-Cholesterol for Liposomes as a Drug Carrier for Hepatocyte-Targeting.
abstract: In this study, three types of galactosylated cholesterol (i.e., gal-PEG194-chol, gal-PEG1000-chol and gal-PEG2000-chol) were synthesized with one terminal of polyethylene glycol of various chain lengths conjugated to the galactoside moiety, and the other terminal conjugated to the cholesterol. The galactose-modified liposomes were prepared by thin film-hydration method and doxorubicin (DOX) was loaded to the liposomes by using a ammonium sulfate gradient procedure. The liposomal formulations with galactosylated cholesterol were characterized. Flow cytometry and laser confocal scanning microscopy analyses showed that the galactose-modified liposomes facilitated the intracellular uptake of liposomes into HepG2 via asialoglycoprotein receptor (ASGP-R) mediated endocytosis. Cytotoxicity assay showed that the cell proliferation inhibition effect of galactose-modified liposomes was higher than that of the unmodified liposomes. Additionally, the study on frozen section of liver showed that the galactose-modified liposomes enhanced the intracellular uptake of liposomes into hepatocytes. Taken together, these results suggested that liposomes containing such galactosylated cholesterol (i.e., gal-PEG-chol), had a great potential as drug delivery carriers for hepatocyte-selective targeting.
authors.forename: Huafang
authors.initials: H
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiao
authors.forename: Shengmiao
authors.initials: S
authors.lastname: Cui
authors.forename: Yuefang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ke
authors.initials: K
authors.lastname: Zeng
authors.forename: Mina
authors.initials: M
authors.lastname: Yan
authors.forename: Chunshun
authors.initials: C
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D037263:Asialoglycoprotein Receptor / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D004317:Doxorubicin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D005690:Galactose / Q000737:chemistry*; D006367:HeLa Cells; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000378:metabolism*; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000493:pharmacokinetics / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D037263:Asialoglycoprotein Receptor; D008081:Liposomes; C118255:polyethylene glycol-cholesterol; D011092:Polyethylene Glycols; D004317:Doxorubicin; D002784:Cholesterol; D005690:Galactose