Novel cyclic peptides facilitating transcellular blood-brain barrier transport of macromolecules in vitro and in vivo.

Animals Biological Transport Blood-Brain Barrier Brain Mice Peptides, Cyclic / pharmacokinetics Rats Transcytosis
Brain delivery Cyclic peptide Macromolecule Phage display technology

Journal

Journal of controlled release : official journal of the Controlled Release Society
ISSN: 1873-4995
Titre abrégé: J Control Release
Pays: Netherlands
ID NLM: 8607908

Informations de publication

Date de publication:
10 05 2020
Historique:
received: 04 12 2019
revised: 26 02 2020
accepted: 02 03 2020
pubmed: 7 3 2020
medline: 18 5 2021
entrez: 6 3 2020
Statut: ppublish

Résumé

Brain delivery of nanoparticles and macromolecular drugs depends on blood-brain barrier (BBB)-permeable carriers. In this study, we searched for cyclic heptapeptides facilitating BBB permeation of M13 phages by phage library screening using a transcellular permeability assay with hCMEC/D3 cell monolayers, a human BBB model. The M13 phage, which is larger than macromolecular drugs and nanoparticles, served as a model macromolecule. The screen identified cyclic heptapeptide SLSHSPQ (SLS) as a human BBB-permeable peptide. The SLS-displaying phage (SLS-phage) exhibited improved permeation across the cell monolayer of monkey and rat BBB co-culture models. The SLS-phage internalized into hCMEC/D3 cells via macropinocytosis and externalized via the exosome excretion pathway. SLS-phage distribution into brain parenchyma was observed in mice after intravenous administration. Moreover, liposome permeated across the BBB as cyclic SLS peptide conjugates. In conclusion, the cyclic SLS heptapeptide is a novel carrier candidate for brain delivery of macromolecular drugs and nanoparticles.

Identifiants

DOI: 10.1016/j.jconrel.2020.03.001 PMID: 32135226
pubmed: 32135226
pii: S0168-3659(20)30140-1
doi: 10.1016/j.jconrel.2020.03.001
pii:
doi:

Substances chimiques

Peptides, Cyclic 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

744-755

Informations de copyright

Copyright © 2020 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest The authors declare no conflict of interest.

Auteurs

Shunsuke Yamaguchi (S)

Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Japan Society for the Promotion of Science, Research Fellowship for Young Scientists, Chiyoda-ku, Tokyo, Japan.

Shingo Ito (S)

Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.

Takeshi Masuda (T)

Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan.

Pierre-Olivier Couraud (PO)

Institut Cochin, INSERM U1016, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.

Sumio Ohtsuki (S)

Department of Pharmaceutical Microbiology, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan; Department of Pharmaceutical Microbiology, Faculty of Life Sciences, Kumamoto University, 5-1 Oe-honmachi, Chuo-ku, Kumamoto 862-0973, Japan. Electronic address: sohtsuki@kumamoto-u.ac.jp.

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Classifications MeSH

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questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Novel cyclic peptides facilitating...
questionsmedicales.fr › Acides aminés, peptides et protéines › Peptides › Peptides cycliques › Novel cyclic peptides facilitating...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Rats › Novel cyclic peptides facilitating...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Exocytose › Transcytose › Novel cyclic peptides facilitating...