title: Nanofiber-based delivery of therapeutic peptides to the brain.
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.
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
authors.forename: Mariarosa
authors.initials: M
authors.lastname: Mazza
authors.forename: Rebecca
authors.initials: R
authors.lastname: Notman
authors.forename: Jamshed
authors.initials: J
authors.lastname: Anwar
authors.forename: Alison
authors.initials: A
authors.lastname: Rodger
authors.forename: Matthew
authors.initials: M
authors.lastname: Hicks
authors.forename: Gary
authors.initials: G
authors.lastname: Parkinson
authors.forename: Dave
authors.initials: D
authors.lastname: McCarthy
authors.forename: Tina
authors.initials: T
authors.lastname: Daviter
authors.forename: Julian
authors.initials: J
authors.lastname: Moger
authors.forename: Natalie
authors.initials: N
authors.lastname: Garrett
authors.forename: Tania
authors.initials: T
authors.lastname: Mead
authors.forename: Michael
authors.initials: M
authors.lastname: Briggs
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Schätzlein
authors.forename: Ijeoma F
authors.initials: IF
authors.lastname: Uchegbu
mesh_terms: D001812:Blood-Brain Barrier / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use; D008958:Models, Molecular; D057139:Nanofibers / Q000737:chemistry*; D050997:Nanomedicine; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D004337:Drug Carriers; D010455:Peptides; D016308:Enkephalin, Leucine-2-Alanine; C040996:enkephalin-Leu, Ala(2)-Arg(6)-