STERICALLY STABILIZED LIPOSOMES - A HYPOTHESIS ON THE MOLECULAR-ORIGIN OF THE EXTENDED CIRCULATION TIMES
STERICALLY STABILIZED LIPOSOMES - A HYPOTHESIS ON THE MOLECULAR-ORIGIN OF THE EXTENDED CIRCULATION TIMES
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DOI：
10.1016/0005-2736(91)90162-2
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发表时间：
1991-11-18
期刊：
影响因子：
--
通讯作者：
PAPAHADJOPOULOS, D
中科院分区：
文献类型：
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作者：
LASIC, DD;MARTIN, FJ;PAPAHADJOPOULOS, D
静脉注射脂质体的治疗应用因其从血流中快速清除以及被肝脏和脾脏（RES）的巨噬细胞吸收而受到限制。然而，最近已经引入了基本上避免RES快速吸收的脂质体。由于这些脂质体表现出显着不同的药代动力学和生物分布，因此出现了新的治疗机会。这些包括增强抗肿瘤药物对肿瘤、炎症部位的功效，以及将配体偶联的脂质体靶向血管外靶点。尽管进行了大量的实验工作，但脂质体避免 RES 快速摄取的能力的机制仍不完全清楚。我们的方法是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的替代方法。我们相信，这种效应可以很容易地通过胶体稳定性的基本原理来解释，至少在定性方面是这样。在这篇文章中，我们提出脂质体的空间稳定性是其循环时间延长的原因。我们认为，稳定性是由于高度水合基团的局部表面浓度造成的，这些基团在空间上抑制脂质体表面各种血液成分的静电和疏水相互作用。
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.