血-脑屏障的存在使得具有治疗作用的绝大多数药物难以入脑，严重影响了脑部疾病的治疗效果。与血-脑屏障相比，血-脑脊液屏障具有一定的通透性，这为药物入脑发挥疗效提供了可能性。目前已有通过瞬时开放血-脑脊液屏障来增加药物入脑的策略，但该方法不具备选择性，并且该侵入性的方法有可能导致大量潜在的神经毒素和其他化学物质进入脑内，这将对中枢神经系统的稳态产生不利影响。本项目拟采用噬菌体展示技术（phage display）筛选可跨越血-脑脊液屏障的靶向肽，以聚乙二醇-聚乳酸羟基乙酸共聚物（PEG-PLGA）纳米粒为载药系统，NAP为模型药物，构建一种新型的噬菌体展示肽介导的脑靶向递药系统并对其脑内递药特性进行评价。该系统的构建模式及相关研究目前国内外未见报道，具有较高的研究意义和社会效益。

Protein and peptide drugs can hardly enter the brain due to the presence of Blood-brain barrier (BBB), seriously affecting the treatment of brain diseases. Blood-cerebrospinal-fluid barrier (BCSFB) is a barrier more likely to overcome compared with BBB and probably provides higher chance to getting access to the brain. Quite a few strategies have been employed to circumvent the BCSFB, including opening the BCSFB, which is invasive and nonselective and may also lead to unwanted entry of a wide range of potential neurotoxins and other agents, which will adversely affect central nervous system (CNS) homeostasis and produce unwanted side effects. This study is to identify peptide ligands that can cross the BCSFB from the system circulation using phage display technology, which may help make drugs more selective, thus providing higher therapeutic efficiency while simultaneously decreasing systemic toxicity. The screened peptide, together with PEG-PLGA copolymer nanoparticles as the drug carrier, and NAP as the model drug, are used to construct a new brain-targeted drug delivery system mediated by the phage-displayed peptide, and he brain drug delivery efficacy will be evaluated. This system and its related research have not been reported at home or abroad. It has high research significance and social benefits.

血-脑屏障的存在使得具有治疗作用的绝大多数药物难以入脑，严重影响了脑部疾病的治疗效果。与血-脑屏障相比，血-脑脊液屏障具有一定的通透性，这为药物入脑发挥疗效提供了可能性。目前已有通过瞬时开放血-脑脊液屏障来增加药物入脑的策略，但该方法不具备选择性，并且该侵入性的方法有可能导致大量潜在的神经毒素和其他化学物质进入脑内，这将对中枢神经系统的稳态产生不利影响。本项目拟采用噬菌体展示技术（phage display）筛选可跨越血-脑脊液屏障的靶向肽，并对其脑内递药特性进行评价。在本研究中，我们使用的是C7C噬菌体展示随机肽库来筛选能跨越血-脑脊液屏障的肽序列。我们首先对M13噬菌体的宿主菌ER2738的生长曲线进行绘制，并对噬菌体体内展示的多个步骤进行了优化。噬菌体展示肽库通过静脉注射给予大鼠，随后从脑脊液中回收噬菌体，扩增后再次通过静脉注射给入大鼠，这样一个循环作为一轮。在多轮体内筛选后，对最后一轮的多个噬菌体进行测序，获得了一条共有序列，该序列将有望协助药物入脑更好地发挥疗效。