Oku N, Namba Y
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka, Japan.
Crit Rev Ther Drug Carrier Syst. 1994;11(4):231-70.
Liposomes have been investigated for use as drug carriers, and many previous studies have demonstrated enhanced efficacy of encapsulated drugs and the reduction of the side effects of drugs so entrapped. In many cases liposomal drugs are administered via the bloodstream. The stability in the bloodstream, clearance, and biodistribution are dependent on the composition, size, and charge of the liposomes. Rigid, small-size (100-200 nm) liposomes tend to be retained in the blood without degradation. Since the conventional liposomes are trapped in the reticuloendothelial system (RES), RES targeting by means of liposomes is easily achieved. This tendency of liposomes, however, is the most serious limitation when their target is not the RES. Many attempts have been made to avoid the RES-trapping and to prolong the circulation time of liposomes with monosialoganglioside GM1, polyethyleneglycol, glucuronide derivatives, and so on. When the targets are tumor tissues, these RES-avoiding, long-circulating liposomes passively accumulate in such tissues due to extravasation through the leaky vasculature in the tumor tissues. Therefore, long-circulating liposomes are useful tools, especially for tumor imaging and therapy. In this review, we show examples and discuss the mechanism of RES avoidance by these modifiers of liposomes, with special focus on the glucuronide as a modifier.
脂质体已被研究用作药物载体，许多先前的研究表明，被包裹药物的疗效得到增强，且所包裹药物的副作用有所减少。在许多情况下，脂质体药物是通过血液循环给药的。其在血液循环中的稳定性、清除率和生物分布取决于脂质体的组成、大小和电荷。刚性的小尺寸（100 - 200纳米）脂质体往往能保留在血液中而不降解。由于传统脂质体会被困在网状内皮系统（RES）中，因此通过脂质体实现RES靶向很容易。然而，当脂质体的靶标不是RES时，这种脂质体的特性就是最严重的限制。人们已经进行了许多尝试，用单唾液酸神经节苷脂GM1、聚乙二醇、葡糖醛酸衍生物等来避免RES捕获并延长脂质体的循环时间。当靶标是肿瘤组织时，这些避免RES捕获的长循环脂质体会由于通过肿瘤组织中渗漏的脉管系统外渗而被动地在这些组织中积累。因此，长循环脂质体是有用的工具，尤其对于肿瘤成像和治疗。在这篇综述中，我们展示实例并讨论这些脂质体修饰剂避免RES捕获的机制，特别关注作为修饰剂的葡糖醛酸。
