Synthesis and application of neoglycolipids for liposome modification.
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.
Murahashi
N
N
Drug Delivery System Institute, Ltd., Science University of Tokyo, Chiba, Japan.
Ishihara
H
H
Sakagami
M
M
Sasaki
A
A
D000818:Animals; D004355:Drug Stability; D006017:Glycolipids / Q000138:chemical synthesis / Q000737:chemistry*; D008024:Ligands; D008081:Liposomes / Q000737:chemistry* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D006017:Glycolipids; D008024:Ligands; D008081:Liposomes