Poste G, Bucana C, Raz A, Bugelski P, Kirsh R, Fidler I J
Cancer Res. 1982 Apr;42(4):1412-22.
Functional and ultrastructural studies of liposomes injected i.v. into inbred C57BL/6N mice were performed to determine whether free liposomes can traverse capillaries. In the liver and spleen, organs with discontinuous (sinusoidal) capillaries, ultrastructural and cell fractionation studies revealed that small (300- to 800-A diameter), sonicated, unilamellar liposomes were more efficient in penetrating liver sinusoids to interact with hepatocytes than were large (0.5- to 10-micrometers) multilamellar liposomes. Ultrastructural studies of the behavior of liposomes in the continuous capillaries of the lungs revealed that circulating phagocytic cells engulf the liposomes in the capillaries. Transcapillary migration of free liposomes was not observed. We conclude that free liposomes are unable to extravasate to reach the alveoli for subsequent engulfment by alveolar macrophages. Instead, liposomes in the lung capillaries are engulfed by circulating blood phagocytes which subsequently migrate to the alveoli to become alveolar macrophages. Experiments on the recruitment of blood monocytes into the lungs subjected to whole- or partial-body X-radiation confirmed that transfer of i.v.-injected liposomes to the alveolar compartment was mediated by blood monocytes. The inability of liposomes to escape from continuous capillaries and their rapid uptake by circulating and fixed phagocytic cells calls into question the feasibility of using liposomes to "target" drugs to cells in extravascular tissues.
通过对静脉注射到近交系C57BL/6N小鼠体内的脂质体进行功能和超微结构研究，以确定游离脂质体是否能够穿过毛细血管。在肝脏和脾脏（具有不连续毛细血管即窦状毛细血管的器官），超微结构和细胞分级分离研究表明，小的（直径300至800埃）、经超声处理的单层脂质体比大的（0.5至10微米）多层脂质体更有效地穿透肝窦与肝细胞相互作用。对脂质体在肺连续毛细血管中行为的超微结构研究表明，循环中的吞噬细胞在毛细血管中吞噬脂质体。未观察到游离脂质体的跨毛细血管迁移。我们得出结论，游离脂质体无法渗出到达肺泡以供肺泡巨噬细胞随后吞噬。相反，肺毛细血管中的脂质体被循环血液中的吞噬细胞吞噬，这些吞噬细胞随后迁移到肺泡成为肺泡巨噬细胞。对全身或局部X射线照射的肺中血液单核细胞募集的实验证实，静脉注射的脂质体向肺泡腔的转移是由血液单核细胞介导的。脂质体无法从连续毛细血管中逸出以及它们被循环和固定的吞噬细胞快速摄取，这使得使用脂质体将药物“靶向”到血管外组织中的细胞的可行性受到质疑。
