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A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine
The clinical use of endogenous neuropeptides has historically been limited due to pharmacokinetic issues, including plasma stability and blood-brain barrier permeability. In this study, we show that the rapidly metabolized Leu-enkephalin (LENK) neuropeptide may become pharmacologically efficient owi...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374102/ https://www.ncbi.nlm.nih.gov/pubmed/30788432 http://dx.doi.org/10.1126/sciadv.aau5148 |
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author | Feng, Jiao Lepetre-Mouelhi, Sinda Gautier, Anne Mura, Simona Cailleau, Catherine Coudore, François Hamon, Michel Couvreur, Patrick |
author_facet | Feng, Jiao Lepetre-Mouelhi, Sinda Gautier, Anne Mura, Simona Cailleau, Catherine Coudore, François Hamon, Michel Couvreur, Patrick |
author_sort | Feng, Jiao |
collection | PubMed |
description | The clinical use of endogenous neuropeptides has historically been limited due to pharmacokinetic issues, including plasma stability and blood-brain barrier permeability. In this study, we show that the rapidly metabolized Leu-enkephalin (LENK) neuropeptide may become pharmacologically efficient owing to a simple conjugation with the lipid squalene (SQ). The corresponding LENK-SQ bioconjugates were synthesized using different chemical linkers in order to modulate the LENK release after their formulation into nanoparticles. This new SQ-based nanoformulation prevented rapid plasma degradation of LENK and conferred on the released neuropeptide a notable antihyperalgesic effect that lasted longer than after treatment with morphine in a rat model of inflammation (Hargreaves test). The biodistribution study as well as the use of brain-permeant and -impermeant opioid receptor antagonists indicated that LENK-SQ NPs act through peripherally located opioid receptors. This study represents a novel nanomedicine approach, allowing the specific delivery of LENK neuropeptide into inflamed tissues for pain control. |
format | Online Article Text |
id | pubmed-6374102 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-63741022019-02-20 A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine Feng, Jiao Lepetre-Mouelhi, Sinda Gautier, Anne Mura, Simona Cailleau, Catherine Coudore, François Hamon, Michel Couvreur, Patrick Sci Adv Research Articles The clinical use of endogenous neuropeptides has historically been limited due to pharmacokinetic issues, including plasma stability and blood-brain barrier permeability. In this study, we show that the rapidly metabolized Leu-enkephalin (LENK) neuropeptide may become pharmacologically efficient owing to a simple conjugation with the lipid squalene (SQ). The corresponding LENK-SQ bioconjugates were synthesized using different chemical linkers in order to modulate the LENK release after their formulation into nanoparticles. This new SQ-based nanoformulation prevented rapid plasma degradation of LENK and conferred on the released neuropeptide a notable antihyperalgesic effect that lasted longer than after treatment with morphine in a rat model of inflammation (Hargreaves test). The biodistribution study as well as the use of brain-permeant and -impermeant opioid receptor antagonists indicated that LENK-SQ NPs act through peripherally located opioid receptors. This study represents a novel nanomedicine approach, allowing the specific delivery of LENK neuropeptide into inflamed tissues for pain control. American Association for the Advancement of Science 2019-02-13 /pmc/articles/PMC6374102/ /pubmed/30788432 http://dx.doi.org/10.1126/sciadv.aau5148 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Feng, Jiao Lepetre-Mouelhi, Sinda Gautier, Anne Mura, Simona Cailleau, Catherine Coudore, François Hamon, Michel Couvreur, Patrick A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine |
title | A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine |
title_full | A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine |
title_fullStr | A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine |
title_full_unstemmed | A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine |
title_short | A new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine |
title_sort | new painkiller nanomedicine to bypass the blood-brain barrier and the use of morphine |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6374102/ https://www.ncbi.nlm.nih.gov/pubmed/30788432 http://dx.doi.org/10.1126/sciadv.aau5148 |
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