Nanofiber-based delivery of therapeutic peptides to the brain.

TitleNanofiber-based delivery of therapeutic peptides to the brain.
Publication TypeJournal Article
Year of Publication2013
AuthorsMazza M, Notman R, Anwar J, Rodger A, Hicks M, Parkinson G, McCarthy D, Daviter T, Moger J, Garrett N, Mead T, Briggs M, Schätzlein AG, Uchegbu IF
JournalACS Nano
Volume7
Issue2
Pagination1016-26
Date Published2013 Feb 26
ISSN1936-086X
KeywordsBlood-Brain Barrier, Brain, Drug Carriers, Enkephalin, Leucine-2-Alanine, Models, Molecular, Nanofibers, Nanomedicine, Peptides, Protein Conformation
Abstract

The delivery of therapeutic peptides and proteins to the central nervous system is the biggest challenge when developing effective neuropharmaceuticals. The central issue is that the blood-brain barrier is impermeable to most molecules. Here we demonstrate the concept of employing an amphiphilic derivative of a peptide to deliver the peptide into the brain. The key to success is that the amphiphilic peptide should by design self-assemble into nanofibers wherein the active peptide epitope is tightly wrapped around the nanofiber core. The nanofiber form appears to protect the amphiphilic peptide from degradation while in the plasma, and the amphiphilic nature of the peptide promotes its transport across the blood-brain barrier. Therapeutic brain levels of the amphiphilic peptide are achieved with this strategy, compared with the absence of detectable peptide in the brain and the consequent lack of a therapeutic response when the underivatized peptide is administered.

DOI10.1021/nn305193d
Alternate JournalACS Nano
PubMed ID23289352
Grant ListBB/F011199/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom