Peptide drug delivery into the central nervous system.
Peptide drug delivery into the central nervous system.
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DOI：
10.1007/978-3-0348-8845-5_3
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
Laszlo Prokai
中科院分区：
文献类型：
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作者：
Laszlo Prokai
中枢神经系统（CNS）的微血管的特点是内皮细胞之间的紧密连接，因此，作为一个连续的脂质双分子层，阻止极性和脂质不溶性物质（如肽）的通过。在微循环的形态成分中表达的高活性酶也代表了有助于中枢神经系统稳态平衡的代谢成分。多肽通常不能从循环血液进入大脑和脊髓，因为它们是高度极性的，脂质不溶性的，代谢不稳定，并且在将体循环与中枢神经系统间质液分开的膜性屏障中，只有极少数多肽存在主动运输系统。因此，这种血脑屏障是基于肽的药物的主要障碍，这些药物可能对对抗影响大脑和脊髓的疾病有用。这篇综述讨论并批判性地评估了侵入性、化学-酶（前药和化学递送/靶向系统）和基于生物载体的方法，以克服这些高活性和多功能分子的血脑屏障，这些分子作为未来一代神经药物非常有吸引力。
The microvasculature of the central nervous system (CNS) is characterized by tight junctions between the endothelial cells and, thus, behaves as a continuous lipid bilayer that prevents the passage of polar and lipid-insoluble substances such as peptides. Highly active enzymes expressed in the morphological compontents of the microcirculation also represent a metabolic component that contributes to the homeostatic balance of the CNS. Peptides generally cannot enter the brain and spinal cord from the circulating blood because they are highly polar and lipid insoluble, metabolically unstable, and active transport systems only exist for very few of them in this membraneous barrier separating the systemic circulation from the interstitital fluid of the CNS. This blood-brain barrier is, therefore, the major obstacle to peptide-based drugs that are potentially useful for combating diseases affecting the brain and spinal cord. This review discusses and critically evaluates invasive, chemical-enzymatic (prodrug and chemical delivery/targeting system) and biological carrier-based approaches to overcome the blood-brain barrier for these highly active and versatile molecules that are very attractive as a future generation of neuropharmaceuticals.