Namba Y, Sakakibara T, Masada M, Ito F, Oku N
Research Laboratories, Nippon Fine Chemical Co., Ltd., Hyogo, Japan.
Chem Pharm Bull (Tokyo). 1990 Jun;38(6):1663-6. doi: 10.1248/cpb.38.1663.
For the purpose of obtaining liposomes with long circulation time in blood, we synthesized 1-O-palmityl-D-glucuronic acid (PGlcUA) and incorporated it into the liposomal membranes. The clearance of the PGlcUA-liposomes composed of dipalmitoylphosphatidylcholine (DPPC), cholesterol, and PGlcUA (40:40:20 as a molar ratio) from blood and their tissue distribution were compared with those of dipalmitoylphosphatidylglycerol (DPPG)-liposomes (DPPC/cholesterol/DPPG = 40:40:20). When [3H]inulin-loaded PGlcUA-liposomes and DPPG-liposomes were intravenously injected into rats, the half-life of the PGlcUA-liposomes in the blood appeared to be 1.7-fold longer than that of DPPG-liposomes. Radioactivities present in plasma and various tissues were measured 22 h after administration of these liposomes, and radioactivity remaining in the plasma was 2.5-fold greater when PGlcUA-liposomes were injected. The distribution pattern of [3H]inulin in PGlcUA-liposomes was similar to that in DPPG-liposomes. The radioactivity recovered in urine was 25% lower in rats treated with PGlcUA-liposomes than in those treated with DPPG-liposomes. Since both PGlcUA- and DPPG-liposomes exhibited similar size distribution and zeta-potential, glucuronic acid, rather than negative charge, on the liposomal surface appears to endow liposomes with a longer circulation time in the bloodstream.
为了获得在血液中具有较长循环时间的脂质体，我们合成了1-O-棕榈酰-D-葡萄糖醛酸（PGlcUA）并将其掺入脂质体膜中。将由二棕榈酰磷脂酰胆碱（DPPC）、胆固醇和PGlcUA（摩尔比为40:40:20）组成的PGlcUA-脂质体从血液中的清除率及其组织分布与二棕榈酰磷脂酰甘油（DPPG）-脂质体（DPPC/胆固醇/DPPG = 40:40:20）进行了比较。当将负载有[3H]菊粉的PGlcUA-脂质体和DPPG-脂质体静脉注射到大鼠体内时，PGlcUA-脂质体在血液中的半衰期似乎比DPPG-脂质体长1.7倍。在给予这些脂质体22小时后测量血浆和各种组织中的放射性，注射PGlcUA-脂质体时血浆中残留的放射性高出2.5倍。[3H]菊粉在PGlcUA-脂质体中的分布模式与在DPPG-脂质体中的相似。用PGlcUA-脂质体处理的大鼠尿液中回收的放射性比用DPPG-脂质体处理的大鼠低25%。由于PGlcUA-脂质体和DPPG-脂质体均表现出相似的大小分布和ζ电位，脂质体表面的葡萄糖醛酸而非负电荷似乎赋予脂质体在血流中更长的循环时间。
