Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery.
Analysis of the fate of systemically administered liposomes and implications for their use in drug delivery.
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发表时间：
1982-04
期刊：
影响因子：
11.2
通讯作者：
George Poste;C. Bucana;Avraham Raz;Peter J. Bugelski;R. Kirsh;I. J. Fidler
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文献类型：
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作者：
George Poste;C. Bucana;Avraham Raz;Peter J. Bugelski;R. Kirsh;I. J. Fidler
静脉注射脂质体的功能和超微结构研究对近交 C57BL/6N 小鼠进行研究以确定游离脂质体是否可以穿过毛细血管。在肝脏和脾脏中，具有不连续（正弦）毛细血管的器官、超微结构和细胞分级分离研究表明，小型（直径为 300 至 800 A）超声处理的单层脂质体比大型（0.5 至 10 微米）多层脂质体更能有效地穿透肝窦与肝细胞相互作用。对肺部连续毛细血管中脂质体行为的超微结构研究表明，循环吞噬细胞吞噬毛细血管中的脂质体。没有观察到游离脂质体的经毛细管迁移。我们得出的结论是，游离脂质体无法外渗到达肺泡，随后被肺泡巨噬细胞吞噬。相反，肺毛细血管中的脂质体被循环的血液吞噬细胞吞噬，随后迁移到肺泡成为肺泡巨噬细胞。在全身或部分身体 X 辐射下将血液单核细胞募集到肺部的实验证实，静脉注射的脂质体向肺泡室的转移是由血液单核细胞介导的。脂质体无法从连续的毛细血管中逸出，并且被循环和固定的吞噬细胞快速摄取，这使得人们对使用脂质体将药物“靶向”血管外组织细胞的可行性产生了疑问。
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.