Tsuji A
Department of Pharmacobio-Dynamics, Faculty of Pharmacertical sciences, Kanazawa University.
Nihon Rinsho. 1998 Mar;56(3):613-8.
Designing drugs (including peptides) with greater lipophilicity are still effective strategy for the enhancement of the permeability across the blood-brain barrier (BBB), which is considered to be lipoidal membrane barrier of endothelial cells which have tight junctions without fenestrations. However, for the development of brain-specific drug delivery for neuroactive drugs, it may be greater promising strategy to utilize the specific influx transporters existing at the BBB for hexoses, amino acids, monocarboxylic acids, amines or to inhibit the functions of the efflux transporters such as P-glycoprotein which pumps out cytotoxic and/or lipophilic drugs. Attractive approach to the delivery of peptides is to design the peptide to be transported across the BBB via ologopeptide specific transporters, via insulin or transferrin receptor-mediated transcytosis, or via adsorptive-mediated transcytosis specific for positively charged peptides.
设计具有更高亲脂性的药物（包括肽类）仍然是增强药物透过血脑屏障（BBB）通透性的有效策略，血脑屏障被认为是由紧密连接且无窗孔的内皮细胞构成的类脂膜屏障。然而，对于开发针对神经活性药物的脑特异性给药系统而言，利用血脑屏障中存在的针对己糖、氨基酸、单羧酸、胺类的特异性摄取转运体，或者抑制诸如P-糖蛋白这类排出细胞毒性和/或亲脂性药物的外排转运体的功能，可能是更具前景的策略。肽类给药的一种有吸引力的方法是设计肽，使其通过寡肽特异性转运体、胰岛素或转铁蛋白受体介导的转胞吞作用，或者通过对带正电荷肽特异性的吸附介导的转胞吞作用穿过血脑屏障。
