鼻腔给药
细胞穿透肽
血脑屏障
化学
脑细胞
鱼精蛋白
细胞
高分子
细胞生物学
生物物理学
神经科学
药理学
生物化学
中枢神经系统
医学
生物
肝素
作者
Tingting Lin,Ergang Liu,Huining He,Meong Cheol Shin,Cheol Moon,Victor C. Yang,Yongzhuo Huang
标识
DOI:10.1016/j.apsb.2016.04.001
摘要
Brain delivery of macromolecular therapeutics (e.g., proteins) remains an unsolved problem because of the formidable blood-brain barrier (BBB). Although a direct pathway of nose-to-brain transfer provides an answer to circumventing the BBB and has already been intensively investigated for brain delivery of small drugs, new challenges arise for intranasal delivery of proteins because of their larger size and hydrophilicity. In order to overcome the barriers and take advantage of available pathways (e.g., epithelial tight junctions, uptake by olfactory neurons, transport into brain tissues, and intra-brain diffusion), a low molecular weight protamine (LMWP) cell-penetrating peptide was utilized to facilitate nose-to-brain transport. Cell-penetrating peptides (CPP) have been widely used to mediate macromolecular delivery through many kinds of biobarriers. Our results show that conjugates of LMWP-proteins are able to effectively penetrate into the brain after intranasal administration. The CPP-based intranasal method highlights a promising solution for protein therapy of brain diseases.
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