Park Y S, Huang L
Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
J Drug Target. 1993;1(4):325-30. doi: 10.3109/10611869308996091.
Lipid A was incorporated into egg phosphatidylcholine (PC)/cholesterol liposomes which were then tested in mice in order to investigate the effect of lipid A on in vivo biodistribution of liposomes. Addition of lipid A up to 3.2 mol% decreased hepatic uptake and slightly increased splenic uptake of liposomes. When more than 3.2 mol% lipid A incorporated into liposomes, hepatic uptake increased with lipid A concentration. Liposomes containing 25 mol% lipid A were rapidly cleared from circulation and taken up mainly by the liver. Ganglioside GM1 or N-monomethoxypoly(ethyleneglycol)-phosphatidylethanolamine (PGE-PE), which is known to prolong the half life of circulating liposomes, was included in liposomes along with lipid A. Lipid A antagonized the effect of GM1 more effectively than that of PEG-PE. This may be due to the different mechanisms of action exerted by GM1 and PEG-PE in liposome circulation. Hepatic uptake of liposomes containing lipid A increased with vesicle size. However, the unique splenic accumulation of large PEG-PE liposomes was only slightly affected by inclusion of a small amount of lipid A (< 7 mol%). These liposomes might be useful for intravenous delivery of antigen to the spleen for increased immune response.
将脂多糖A掺入卵磷脂酰胆碱（PC）/胆固醇脂质体中，随后在小鼠体内进行测试，以研究脂多糖A对脂质体体内生物分布的影响。添加高达3.2 mol%的脂多糖A可降低脂质体的肝脏摄取，并略微增加脾脏摄取。当超过3.2 mol%的脂多糖A掺入脂质体时，肝脏摄取随脂多糖A浓度增加。含有25 mol%脂多糖A的脂质体从循环中迅速清除，主要被肝脏摄取。已知可延长循环脂质体半衰期的神经节苷脂GM1或N-单甲氧基聚（乙二醇）-磷脂酰乙醇胺（PGE-PE）与脂多糖A一起包含在脂质体中。脂多糖A对GM1的作用拮抗比PEG-PE更有效。这可能是由于GM1和PEG-PE在脂质体循环中发挥作用的机制不同。含有脂多糖A的脂质体的肝脏摄取随囊泡大小增加。然而，大PEG-PE脂质体独特的脾脏积累仅受到少量脂多糖A（<7 mol%）包含的轻微影响。这些脂质体可能有助于将抗原静脉内递送至脾脏以增强免疫反应。
