Murahashi N, Sasaki A
Drug Delivery System Institute, Science University of Tokyo, Chiba, Japan.
Biol Pharm Bull. 1996 Mar;19(3):418-23. doi: 10.1248/bpb.19.418.
We studied the in vivo behavior of galactosyllipid-modified liposomes for targeting the asialoglycoprotein receptor present on the surface of liver parenchymal cells. We examined the effects of the lipid composition of liposomes on the in vivo behavior of galactosyllipid-modified liposomes, and found good accumulation in the liver of liposomes of a high cholesterol content and liposomes made of lipids of a high gel-liquid crystalline phase transition temperature. The amount of modification with the galactosyllipid derivative required for effective targeting to the liver was found to be more than 5% of the total lipids. The concentration of galactosyllipid-modified liposomes was lower than that of control liposomes in all the organs except for the liver, showing high selectivity of galactosyllipid-modified liposomes for the liver. Hepatic accumulation of liposomes was inhibited by preinjection of asialofetuin. This result suggests that hepatic accumulation of ¿8-(2-hexadecyloctadecanoylamido)-3,6-dioxaoctyl¿-beta-D-gal actoside (Gal-t-psa) liposome was involved with the asialoglycoprotein receptor in the liver. Therefore, it was concluded that our neogalactolipid-modified liposomes are useful for selective delivery to the liver.
我们研究了半乳糖脂修饰脂质体在体内的行为，以靶向肝实质细胞表面存在的去唾液酸糖蛋白受体。我们考察了脂质体的脂质组成对半乳糖脂修饰脂质体体内行为的影响，发现胆固醇含量高的脂质体以及由具有高凝胶-液晶相变温度的脂质制成的脂质体在肝脏中有良好的蓄积。发现有效靶向肝脏所需的半乳糖脂衍生物修饰量超过总脂质的5%。除肝脏外，在所有器官中半乳糖脂修饰脂质体的浓度均低于对照脂质体，这表明半乳糖脂修饰脂质体对肝脏具有高选择性。预先注射去唾液酸胎球蛋白可抑制脂质体在肝脏的蓄积。该结果表明，8-(2-十六烷基十八烷酰胺基)-3,6-二氧杂辛基-β-D-半乳糖苷（Gal-t-psa）脂质体在肝脏的蓄积与肝脏中的去唾液酸糖蛋白受体有关。因此，得出结论，我们的新半乳糖脂修饰脂质体可用于向肝脏的选择性递送。
