pH-sensitive, plasma-stable liposomes with relatively prolonged residence in circulation.
pH-sensitive, plasma-stable liposomes with relatively prolonged residence in circulation.
复制标题
pH 敏感、血浆稳定的脂质体，在循环中的停留时间相对较长。
DOI：
10.1016/0005-2736(90)90284-u
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Huang,L
中科院分区：
文献类型：
--
作者：
Liu,D;Huang,L
由不饱和磷脂酰乙醇胺（PE）组成的酸敏感脂质体是靶细胞胞质递送的有效载体。我们最近发现，由二油酰-PE（DOPE）和二棕榈酰琥珀酰甘油DPSG组成的脂质体在暴露于人血浆后保持酸敏感性。在目前的工作中，我们已经扩大了这些观察，以探讨神经节苷脂GM 1对这些脂质体的血液停留时间的作用。由DOPE和DPSG（4：1，摩尔比）组成的小单层脂质体（直径<100 nm），随着GM 1含量的增加，其酸敏感性逐渐降低。然而，对酸的部分敏感性（在pH 4下包封的内容物的40-50%释放）可以保持高达5%GM 1，甚至对于已经暴露于人血浆的脂质体。在人血浆存在下，在脂质组合物中加入GM 1仅略微增加了截留内容物的释放。通过追踪包埋的125 I标记的酪氨酰菊粉标记物，研究了静脉注射含GM 1的脂质体在Balb/c小鼠中的生物分布。包含高达5%的GM 1表现出短暂的血液水平的增加和伴随的肝脏和脾脏的脂质体摄取的减少。因此，这些脂质体是pH敏感的、血浆稳定的，并且在循环中显示出相对延长的停留时间。它们是潜在的重要的体内药物载体。
Acid-sensitive liposomes composed of unsaturated phosphatidylethanolamine (PE) are efficient vehicles for cytoplasmic delivery of the target cells. We have recently shown that liposomes composed of dioleoyl-PE (DOPE) and dipalmitoylsuccinylglycerol DPSG retain the acid-sensitivity after exposure to human plasma. In the present work, we have extended these observations to investigate the role of ganglioside GM1on the blood residence time of these liposomes. Small (d≈ 100nm) unilamellar liposomes composed of DOPE and DPSG (4:1, molar ratio) became progressively less acid-sensitivie when increasing amounts of GM1were included in the lipid composition. However, partial sensitivity to acid (40–50% release of entrapped contents at pH 4) could be retained up to 5% GM1, even for liposomes which had been exposed to human plasma. Inclusion of GM1in the lipid composition only slightly increased the release of entrapped contents in the presence of human plasma. The biodistribution of i.v. injected GM1-containing liposomes was studied by following the entrapped125I-labeled tyraminylinulin marker in Balb/c mice. Inclusion of up to 5% GM1showed a transient increase in the blood level and a concomitant decrease of liver and spleen uptake of liposomes. Thus, these liposomes are pH-sensitive, plasma-stable and show a relatively prolonged residence time in circulation. They are potentially significant drug carriers in vivo.