Nose-to-brain (N-to-B) delivery offers to protein and peptide drugs the possibility to reach the brain in a non-invasive way. This article is a comprehensive review of the state-of-the-art of this emerging peptide delivery route, as well as of the challenges associated to it. Emphasis is given on the potential of nanosized drug delivery carriers to enhance the direct N-to-B transport of protein or peptide drugs. In particular, polymer- and lipid- based nanocarriers are comparatively analyzed in terms of the influence of their physicochemical characteristics and composition on their in vivo fate and efficacy. The use of biorecognitive ligands and permeation enhancers in order to enhance their brain targeting efficiency is also discussed. The article concludes highlighting the early stage of this research field and its still unveiled potential. The final message is that more explicatory PK/PD studies are required in order to achieve the translation from preclinical to the clinical development phase.

鼻子到大脑（N到B）的输送为蛋白质和肽类药物提供了以非侵入性方式到达大脑的可能性。本文是对这种新兴肽递送途径的最新技术以及与之相关的挑战的全面综述。重点介绍了纳米级药物递送载体增强蛋白质或肽类药物从N到B的直接N-B转运的潜力。特别是，基于聚合物和脂质的纳米载体在其理化特性和组成对其体内的影响方面进行了比较分析。命运与功效。还讨论了使用生物识别配体和渗透促进剂以增强其脑靶向效率。文章的结尾部分着重介绍了该研究领域的早期阶段及其仍具有的潜力。最后的信息是，需要进行更多的探索性PK / PD研究，以实现从临床前到临床开发阶段的翻译。