Illum Lisbeth
Identity, 19 Cavendish Crescent North, the Park, Nottingham NG7 1BA, UK.
J Pharm Pharmacol. 2004 Jan;56(1):3-17. doi: 10.1211/0022357022539.
The blood-brain barrier that segregates the brain interstitial fluid from the circulating blood provides an efficient barrier for the diffusion of most, especially polar, drugs from the blood to receptors in the central nervous system (CNS). Hence limitations are evident in the treatment of CNS diseases, such as Parkinson's and Alzheimer's diseases, especially exploiting neuropeptides and similar polar and large molecular weight drugs. In recent years interest has been expressed in the use of the nasal route for delivery of drugs to the brain, exploiting the olfactory pathway. A wealth of studies has reported proof of nose-to-brain delivery of a range of different drugs in animal models, such as the rat. Studies in man have mostly compared the pharmacological effects (e.g. brain functions) of nasally applied drugs with parenterally applied drugs and have shown a distinct indication of direct nose-to-brain transport. Recent studies in volunteers involving cerebrospinal fluid sampling, blood sampling and pharmacokinetic analysis after nasal, and in some instances parenteral administration of different drugs, have in my opinion confirmed the likely existence of a direct pathway from nose to brain.
血脑屏障将脑间质液与循环血液分隔开来，为大多数药物，尤其是极性药物从血液扩散到中枢神经系统（CNS）中的受体提供了有效的屏障。因此，在治疗中枢神经系统疾病，如帕金森病和阿尔茨海默病时，尤其是在利用神经肽和类似的极性及大分子药物方面存在明显的局限性。近年来，人们对利用嗅觉途径通过鼻腔给药将药物输送到大脑产生了兴趣。大量研究报告了在动物模型（如大鼠）中一系列不同药物鼻脑给药的证据。人体研究大多比较了鼻腔给药和胃肠外给药药物的药理作用（如脑功能），并显示出直接鼻脑转运的明显迹象。在我看来，最近在志愿者中进行的研究，包括在鼻腔给药以及在某些情况下胃肠外给药不同药物后进行脑脊液采样、血液采样和药代动力学分析，证实了从鼻子到大脑可能存在直接途径。
