title: Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides.
abstract: 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.
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Lin
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Ergang
authors.initials: E
authors.lastname: Liu
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Huining
authors.initials: H
authors.lastname: He
authors.affiliation: College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109-1065, USA; College of Pharmacy and Research Institute of Pharmaceutical Sciences, Gyeongsang National University, Jinju, Gyeongnam 660-701, Republic of Korea.
authors.forename: Meong Cheol
authors.initials: MC
authors.lastname: Shin
authors.affiliation: College of Pharmacy, Sunchon National University, Suncheon, Jeonnam 540-950, Republic of Korea.
authors.forename: Cheol
authors.initials: C
authors.lastname: Moon
authors.affiliation: Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnosis, School of Pharmacy, Tianjin Medical University, Tianjin 300070, China; College of Pharmacy, The University of Michigan, Ann Arbor, MI 48109-1065, USA.
authors.forename: Victor C
authors.initials: VC
authors.lastname: Yang
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yongzhuo
authors.initials: Y
authors.lastname: Huang
keywords: Blood–brain barrier; Brain targeting; Cell-penetrating peptide; Intranasal protein delivery; Low molecular weight  protamine