Can nasal drug delivery bypass the blood-brain barrier?: questioning the direct transport theory.
Can nasal drug delivery bypass the blood-brain barrier?: questioning the direct transport theory.
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DOI：
10.2165/00126839-200708030-00001
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发表时间：
2007-01-01
期刊：
影响因子：
3
通讯作者：
van den Berg, Mascha P
中科院分区：
文献类型：
--
作者：
Merkus, Frans W H M;van den Berg, Mascha P
在过去的几十年中，已经广泛研究了鼻腔和CNS之间通过嗅觉神经元的连接，关于其作为直接药物转运途径至CSF和脑的可行性。这种药物转运途径已经获得了很大的兴趣，因为它可以绕过血脑屏障（BBB），阻止一些药物进入大脑。对主要报告动物实验的约100篇已发表论文进行了综述，以评价所使用的实验设计和产生的结果是否提供了足够的药代动力学信息，以评估所研究的药物是否直接从嗅觉区转运至CNS。在分析中，动物和人类的嗅觉区域之间的巨大解剖差异以及所使用的实验条件进行了评估。本文的目的是建立这种直接运输途径在人类中的可行性的实际证据。12篇论文提出了一个合理的实验设计，研究直接鼻中枢神经系统的药物运输的基础上，作者的标准。其中，只有两项大鼠研究能够提供可视为从鼻直接转运至CNS的指示的结果。未发现药代动力学证据支持以下声明：与相似剂量条件下相同药物的静脉给药相比，人体经鼻给药将导致药物向大脑靶部位的递送增强。
The connection between the nasal cavity and the CNS by the olfactory neurones has been investigated extensively during the last decades with regard to its feasibility to serve as a direct drug transport route to the CSF and brain. This drug transport route has gained much interest as it may circumvent the blood-brain barrier (BBB), which prevents some drugs from entering the brain. Approximately 100 published papers mainly reporting animal experiments were reviewed to evaluate whether the experimental design used and the results generated provided adequate pharmacokinetic information to assess whether the investigated drug was transported directly from the olfactory area to the CNS. In the analysis the large anatomical differences between the olfactory areas of animals and humans and the experimental conditions used were evaluated. The aim of this paper was to establish the actual evidence for the feasibility of this direct transport route in humans. Twelve papers presented a sound experimental design to study direct nose to CNS transport of drugs based on the authors' criteria. Of these, only two studies in rats were able to provide results that can be seen as an indication for direct transport from the nose to the CNS. No pharmacokinetic evidence could be found to support a claim that nasal administration of drugs in humans will result in an enhanced delivery to their target sites in the brain compared with intravenous administration of the same drug under similar dosage conditions.