Nose-to-brain delivery of macromolecules mediated by cell-penetrating peptides

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 delive...

Full description

Saved in:
Bibliographic Details
Published in:Acta pharmaceutica Sinica. B 2016-07, Vol.6 (4), p.352-358
Main Authors: Lin, Tingting, Liu, Ergang, He, Huining, Shin, Meong Cheol, Moon, Cheol, Yang, Victor C, Huang, Yongzhuo
Format: Article
Language:English
Subjects:
barrier
Blood–brain barrier
Brain targeting
Cell-penetrating peptide
delivery
Brain
Intranasal
Intranasal protein delivery
Low molecular weight  protamine
molecular
peptide
Low
protamine
Blood–brain
protein
Short Communication
targeting
Cell-penetrating
weight
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2211-3835
2211-3843
DOI:10.1016/j.apsb.2016.04.001