中文摘要
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。通过前期实验我们筛选获得了能跨越血-脑脊液屏障的十二肽(T12,TPSYDTYAAELR),本项目拟将T12肽修饰于聚乙二醇-聚乳酸羟基乙酸共聚物(PEG-PLGA)纳米粒表面,以石杉碱甲为模型药物,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。此外,本申请拟对T12肽跨血-脑脊液屏障的机理进行初探。本申请的递药系统的构建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。
英文摘要
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. A dodecapeptide (named as T12,TPSYDTYAAELR) was screened from our previous study. T12 is a promising motif which can cross the BCSFB from system circulation. In this present study, T12, together with PEG-PLGA copolymer nanoparticles as the drug carrier, and huperzine-A as the model drug, is used to construct a new brain-targeted drug delivery system mediated by the phage-displayed peptide, and the brain drug delivery efficacy will be evaluated. Furthermore, primary exploration of the mechanism of T12 crossing BCSFB will be conducted. This new drug delivery system and its related research have not been reported at home or abroad. It has high research significance and social benefits.
