Synthesis and Application of Neoglycolipids for Liposome Modification.

Abstract

We synthesized various glycolipid derivatives and examined the in vivo behaviors of liposomes modified with these novel glycolipid derivatives. Gal-t-psa (1,¿8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl¿-beta-D- galactoside), Lac-t-psa (3, 8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl beta-D-lactoside) and GalNAc-t-psa (4, 8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl 2-acetamido-beta-D-galactopyranoside) modified liposomes were recognized by the liver. Lac-t-psa (3) modified liposome was accumulated to the highest degree, followed by GalNAc-t-psa (4) modified liposome and then Gal-t-psa (1) modified liposome. The intrahepatic distributions of Gal-t-psa (1), GalNAc-t-psa (4), Glc-t-psa (2, 8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl beta-D-glucopyranoside) and Lac-t-psa (3) modified liposomes were investigated. GalNAc-t-psa (4) and Lac-t-psa (3) modified liposome were accumulated to greater extents than Gal-t-psa (1) modified liposome in hepatic parenchymal cells. The intrahepatic distribution of these liposomes showed that Lac-t-psa (3) and GalNAc-t-psa (4) were preferable to Gal-t-psa (1) for the selective delivery of liposomes to hepatic parenchymal cells.

Specific interaction of lectins with liposomes and monolayers bearing neoglycolipids

“…The neoglycolipids were formed of Guerbet alcohol (G 28 ) directly bound to a sugar moiety (N-acetylglucosamine) or through a triethylene glycol (E 3 ) spacer (N-acetylglucosamine, ␣or ␤-fucose). The ␤-N-acetylglucosamine derivatives, GlcNAcG 28 (M w 613.97) and GlcNAcE 3 G 28 (M w 746.13), were synthesized according to the previously described route (Murahashi et al, 1997). The synthesis routes to fucose derivatives (M w 689.08) led either to the pure ␤-FucE 3 G 28 or to a mixture of the ␣and ␤-anomers (8.4:1.6), later referred to as ␣-FucE 3 G 28 in this paper (Faivre et al, 2001).…”

“…Also, Shimada et al (1997) showed that liposome surface-exposed galactose residues, attached to the distal end of a poly(ethylene glycol) chain anchored in the liposomal bilayer were effectively recognized by the galactose particle receptor on the Kupffer cells. In another work, by Murahashi et al (1997) it was reported that the recognition of neoglycolipid-bearing liposomes by liver cells took place. Apart from their ability to adsorb on a liposome surface and anchor to its bilayer membrane (Sancho et al, 1993), these neoglycolipids were found to be able to form supramolecular assemblies such as vesicles (Emmanouil et al, 1998;Blanzat et al, 1999), or nanoparticles formed of spherical sugar-persubstituted dendrimers (sugar balls) that exhibit a highly ordered structure with saccharide arrays on their periphery (Esumi et al, 2000).…”

Molecular recognition on the supported and on the air/water interface-spread protein monolayers

“…Shimada et al [68] have shown that liposome surface-exposed galactose residues, attached to the end of the poly(ethylene glycol) chain anchored in the liposomal bilayer were effectively recognized by the galactose receptor on the Kupffer cells. In another work, Murahashi et al [69] reported the recognition of neoglycolipidbearing liposomes by liver cells.…”

Sensitive detection of ultra-weak adhesion states of vesicles by interferometric microscopy

“…The lipid 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) was purchased from Avanti Polar Lipids (Alabaster, AL, USA). The neoglycolipid was formed of Guerbet alcohol (G 28 ) bound to a sugar (N-acetylglucosamine) through a triethylene glycol (E 3 ) spacer (N-acetylglucosamine) according to a previously described synthesis 35 (see Fig. 2).…”