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

Journal of Controlled Release : Official Journal of the Controlled Release Society
Shunsuke YamaguchiSumio Ohtsuki

Abstract

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.

References

Jul 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·L J ArnoldN O Kaplan
Jan 16, 2002·Drug Discovery Today·William M Pardridge
Oct 29, 2002·Annals of Neurology·Ertugrul KilicMathias Bähr
Apr 5, 2003·Stroke; a Journal of Cerebral Circulation·Ulkan KilicMathias Bähr
Aug 13, 1965·Science·R W ATCHISONW M HAMMON
Feb 18, 2005·NeuroRx : the Journal of the American Society for Experimental NeuroTherapeutics·William M Pardridge
Jun 7, 2005·British Journal of Pharmacology·Simon W JonesMark A Lindsay
Sep 6, 2005·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·B B WekslerP O Couraud
Feb 7, 2006·International Journal of Pharmaceutics·Yasuyuki SadzukaTakashi Sonobe
Jul 14, 2007·Biochimica Et Biophysica Acta·Alessandra K CardozoFabienne Maurer
Sep 13, 2008·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Caroline Palm-ApergiMattias Hällbrink
Dec 23, 2008·Nature Biotechnology·Kevin D FoustBrian K Kaspar
Jun 6, 2009·Cellular and Molecular Life Sciences : CMLS·Hervé Hillaireau, Patrick Couvreur
Feb 16, 2010·Biochimica Et Biophysica Acta·Isabel D AlvesSandrine Sagan
Aug 26, 2010·Annals of Biomedical Engineering·Melissa J SimonBarclay Morrison
Nov 4, 2010·Molecular Therapy : the Journal of the American Society of Gene Therapy·Julia V GeorgievaInge S Zuhorn
Dec 21, 2010·Trends in Pharmacological Sciences·Wouter P R Verdurmen, Roland Brock
Mar 23, 2011·Immunology and Cell Biology·Jet Phey Lim, Paul A Gleeson
Oct 5, 2011·Proceedings of the National Academy of Sciences of the United States of America·Abhijit MishraGerard C L Wong
Mar 28, 2012·The Journal of Cell Biology·Masamichi NagaeJunichi Takagi
Jul 25, 2012·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yan MaYu-Hui Zhang
Jul 6, 2013·Nature Communications·Marcel GrappRobert Steinfeld
Jul 9, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Luba Kozlovskaya, David Stepensky
Oct 22, 2013·International Journal of Nanomedicine·Jong-Wook LeeKwan Hyi Lee
Nov 12, 2013·Archives of Pharmacal Research·Karen C Liu, Yoon Yeo
Dec 3, 2013·Journal of Controlled Release : Official Journal of the Controlled Release Society·Feihu WangFang Jin
Jan 22, 2014·Human Gene Therapy·Ronald G Crystal
Feb 4, 2014·Biochemical and Biophysical Research Communications·Tomohiro AsaiNaoto Oku
Dec 6, 2014·Proceedings of the National Academy of Sciences of the United States of America·Wei Xia, Timothy A Springer
Oct 24, 2015·Angewandte Chemie·Benjamí Oller-SalviaMeritxell Teixidó
Jan 20, 2016·International Journal of Pharmaceutics·Yining XuYuan Huang

❮ Previous
Next ❯

Citations

Aug 9, 2020·Frontiers in Molecular Neuroscience·Travis C Jackson, Patrick M Kochanek
Nov 3, 2020·PloS One·Koichi EguchiYasuyuki Igarashi
Jan 21, 2021·Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology·Xue ZhouXinli Liu
Jun 5, 2021·Cellular and Molecular Neurobiology·Oandy NaranjoMichal Toborek

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Related Papers

Nihon yakurigaku zasshi. Folia pharmacologica Japonica
Shinsuke Nakagawa, Masami Niwa
Hepatology : Official Journal of the American Association for the Study of Liver Diseases
K D MullenA J McCullough
© 2021 Meta ULC. All rights reserved