Lasic D D, Martin F J, Gabizon A, Huang S K, Papahadjopoulos D
Liposome Technology, Inc., Menlo Park, CA.
Biochim Biophys Acta. 1991 Nov 18;1070(1):187-92. doi: 10.1016/0005-2736(91)90162-2.
Therapeutic applications of intravenously injected liposomes have been limited by their rapid clearance from the bloodstream and their uptake by the macrophage cells of the liver and spleen (RES). Recently, however, liposomes which substantially evade the rapid uptake by the RES have been introduced. Since these liposomes exhibit dramatically different pharmacokinetics and biodistribution, new therapeutic opportunities have appeared. These include enhanced efficacy of antineoplastic agents against tumors, sites of inflammation, and targeting ligand-coupled liposomes to extravascular targets. Despite extensive experimental work, the mechanism underlying the ability of liposomes to avoid the rapid uptake by the RES is still not fully understood. Our approach is an alternative to seeking the answers in complex differential interactions of liposomes with various components of blood. We believe that the effect can be easily explained, at least in qualitative terms, by the fundamental principles of colloid stability. In this communication, we propose that steric stabilization of liposomes is responsible for their prolonged circulation times. We propose that stabilization results from local surface concentration of highly hydrated groups that sterically inhibit both electrostatic and hydrophobic interactions of a variety of blood components at the liposome surface.
静脉注射脂质体的治疗应用受到其从血液中快速清除以及被肝脏和脾脏的巨噬细胞（RES）摄取的限制。然而，最近已经引入了基本上能避免被RES快速摄取的脂质体。由于这些脂质体表现出显著不同的药代动力学和生物分布，新的治疗机会已经出现。这些机会包括抗肿瘤药物对肿瘤、炎症部位的疗效增强，以及将配体偶联脂质体靶向血管外靶点。尽管进行了广泛的实验工作，但脂质体避免被RES快速摄取的能力背后的机制仍未完全理解。我们的方法是一种替代方案，无需在脂质体与血液各种成分的复杂差异相互作用中寻找答案。我们认为，至少在定性方面，这种效应可以通过胶体稳定性的基本原理轻松解释。在本通讯中，我们提出脂质体的空间稳定作用是其循环时间延长的原因。我们提出这种稳定作用源于高度水合基团的局部表面浓度，这些基团在空间上抑制了脂质体表面各种血液成分的静电和疏水相互作用。
