Characteristics of compounds that cross the blood-brain barrier.
Characteristics of compounds that cross the blood-brain barrier.
复制标题
穿过血脑屏障的化合物的特征。
DOI：
10.1186/1471-2377-9-s1-s3
复制
发表时间：
2009-06-12
期刊：
影响因子：
2.6
通讯作者：
Banks WA
中科院分区：
文献类型：
--
作者：
Banks WA
物质通过多种机制穿过血脑屏障（BBB）。这些包括跨膜扩散、饱和转运蛋白、吸附性内吞作用和细胞外途径。在这里，我们专注于两个机制，特别是重要的药物输送的主要特点：跨膜扩散和转运。跨膜扩散是不饱和的，取决于第一次分析，物质的物理化学特性。然而，脑-血流出系统、酶活性、血浆蛋白结合和脑血流量可以极大地改变穿过BBB的物质的量。转运系统使配体的摄取增加约10倍，并通过生理事件和疾病状态进行修饰。迄今为止，临床使用的大多数药物是通过跨膜扩散穿过BBB的小的脂溶性分子。然而，近年来已经描述了许多开发中的药物递送策略的靶向肽、调节蛋白、寡核苷酸、糖蛋白和转运体的酶。我们讨论了两个新发现的转运药物的例子：硫代磷酸寡核苷酸和酶。
Substances cross the blood-brain barrier (BBB) by a variety of mechanisms. These include transmembrane diffusion, saturable transporters, adsorptive endocytosis, and the extracellular pathways. Here, we focus on the chief characteristics of two mechanisms especially important in drug delivery: transmembrane diffusion and transporters. Transmembrane diffusion is non-saturable and depends, on first analysis, on the physicochemical characteristics of the substance. However, brain-to-blood efflux systems, enzymatic activity, plasma protein binding, and cerebral blood flow can greatly alter the amount of the substance crossing the BBB. Transport systems increase uptake of ligands by roughly 10-fold and are modified by physiological events and disease states. Most drugs in clinical use to date are small, lipid soluble molecules that cross the BBB by transmembrane diffusion. However, many drug delivery strategies in development target peptides, regulatory proteins, oligonucleotides, glycoproteins, and enzymes for which transporters have been described in recent years. We discuss two examples of drug delivery for newly discovered transporters: that for phosphorothioate oligonucleotides and for enzymes.