Scherphof G L, Daemen T, Spanjer H H, Roerdink F H
Laboratory of Physiological Chemistry, University of Groningen, The Netherlands.
Lipids. 1987 Nov;22(11):891-6. doi: 10.1007/BF02535550.
In this paper, we report on the in vivo behavior of liposomes as a function of their size and composition. It is emphasized that by varying these parameters we can influence not only the rate of blood elimination but also the intrahepatic destination of the liposomes. Thus, we show that small liposomes with diameters well below 100 nm can reach and be internalized by the parenchymal cells of the liver, i.e. the hepatocytes. The rate and the extent at which this occurs depends on the liposomal composition. With respect to the application of liposomes as a drug carrier system in anticancer therapy, we put emphasis on the liver macrophage, i.e. the Kupffer cell, as a target cell. Large liposomes with diameters well over 100 nm exclusively are taken up by these cells as far as hepatic uptake is concerned. By encapsulation within liposomes, a drug may be delivered specifically to these macrophages; this will prevent its rapid excretion from the body and/or undesired accumulation in other cell types. Two examples of the way in which this condition may be exploited are presented. First, we demonstrate the formation of intracellular depots in the macrophages of the cytostatic drug 5-fluorodeoxyuridine (FUdR), thus preventing the rapid metabolism of the drug by the hepatocytes and allowing its sustained release from the macrophages and subsequent uptake by adjacent metastatic tumor cells.(ABSTRACT TRUNCATED AT 250 WORDS)
在本文中，我们报告了脂质体在体内的行为与其大小和组成的关系。需要强调的是，通过改变这些参数，我们不仅可以影响血液清除率，还能影响脂质体在肝内的归宿。因此，我们发现直径远低于100 nm的小脂质体能够到达肝脏实质细胞（即肝细胞）并被其内化。这一过程发生的速率和程度取决于脂质体的组成。关于脂质体作为抗癌治疗药物载体系统的应用，我们着重关注肝脏巨噬细胞，即库普弗细胞，将其作为靶细胞。就肝脏摄取而言，直径远超过100 nm的大脂质体仅被这些细胞摄取。通过包裹在脂质体内，药物可以特异性地递送至这些巨噬细胞；这将防止药物从体内快速排泄和/或在其他细胞类型中产生不期望的蓄积。本文给出了利用这种情况的两个例子。首先，我们证明了在巨噬细胞中形成了细胞生长抑制剂5-氟脱氧尿苷（FUdR）的细胞内贮库，从而防止药物被肝细胞快速代谢，并使其从巨噬细胞中持续释放，随后被邻近的转移性肿瘤细胞摄取。（摘要截短于250字）
