Gotfredsen C F, Frøkjaer S, Hjorth E L, Jørgensen K D, Debroux-Guisset M C
Biochem Pharmacol. 1983 Nov 15;32(22):3381-7. doi: 10.1016/0006-2952(83)90366-0.
Small unilamellar liposomes containing bovine serum albumin were prepared by a new double-emulsion technique and administered to mice and rats in intravenous injections. The elimination of intact liposomes, the association of phospholipid marker with lipoproteins, and the appearance of released internal marker and its degradation products were followed by column chromatography of plasma samples. In vitro labelled lipoproteins were administered to the animals in intravenous injections together with free bovine serum albumin and the elimination of the two substances was studied by closely related techniques. The clearance of intact PC:PS (4:1) liposomes from plasma was biphasic and much faster than that of labelled lipoproteins and bovine serum albumin either originating from liposomes or injected as such. The second elimination phase for these liposomes was barely detectable by our analytical methods. In contrast, DSPC:CHOL (2:1) liposomes showed a very significant second-phase elimination, with a half-life of 12 hr for the intact liposomes. In tissue distribution studies in mice, the major accumulation of liposomal markers was found in the liver and spleen, and less in the kidneys and intestinal wall. Uptake into liver and spleen appeared to be due to the uptake of intact liposomes, whereas the uptake into kidneys and gut wall was caused by the uptake of liposomal degradation products. The uptake of PC:PS (4:1) liposomes into the liver was higher than that of DSPC:CHOL (2:1) liposomes; the opposite was the case with their uptake into the spleen. In rats, too, liposomes of different compositions showed significant variations in stability and in plasma half-lives of intact liposomes. Generally, there was a considerable increase in the liposomal stability in the presence of cholesterol and when use was made of a phospholipid with a high transition temperature.
采用一种新的双乳液技术制备了含有牛血清白蛋白的小单层脂质体，并通过静脉注射给予小鼠和大鼠。通过对血浆样品进行柱色谱分析，追踪完整脂质体的清除情况、磷脂标记物与脂蛋白的结合情况以及释放的内部标记物及其降解产物的出现情况。将体外标记的脂蛋白与游离牛血清白蛋白一起通过静脉注射给予动物，并采用密切相关的技术研究这两种物质的清除情况。完整的PC:PS（4:1）脂质体从血浆中的清除是双相的，并且比源自脂质体或直接注射的标记脂蛋白和牛血清白蛋白的清除速度快得多。我们的分析方法几乎检测不到这些脂质体的第二个清除阶段。相比之下，DSPC:CHOL（2:1）脂质体显示出非常显著的第二阶段清除，完整脂质体的半衰期为12小时。在小鼠的组织分布研究中，脂质体标记物主要积聚在肝脏和脾脏中，在肾脏和肠壁中的积聚较少。肝脏和脾脏中的摄取似乎是由于完整脂质体的摄取，而肾脏和肠壁中的摄取是由脂质体降解产物的摄取引起的。PC:PS（4:1）脂质体在肝脏中的摄取高于DSPC:CHOL（2:1）脂质体；它们在脾脏中的摄取情况则相反。在大鼠中，不同组成的脂质体在稳定性和完整脂质体的血浆半衰期方面也表现出显著差异。一般来说，在存在胆固醇的情况下以及使用具有高转变温度的磷脂时，脂质体的稳定性会有相当大的提高。
