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Nano-engineered microcapsules boost the treatment of persistent pain

Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and rele...

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Autores principales: Kopach, Olga, Zheng, Kayiu, Dong, Luo, Sapelkin, Andrei, Voitenko, Nana, Sukhorukov, Gleb B., Rusakov, Dmitri A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796488/
https://www.ncbi.nlm.nih.gov/pubmed/29383961
http://dx.doi.org/10.1080/10717544.2018.1431981
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author Kopach, Olga
Zheng, Kayiu
Dong, Luo
Sapelkin, Andrei
Voitenko, Nana
Sukhorukov, Gleb B.
Rusakov, Dmitri A.
author_facet Kopach, Olga
Zheng, Kayiu
Dong, Luo
Sapelkin, Andrei
Voitenko, Nana
Sukhorukov, Gleb B.
Rusakov, Dmitri A.
author_sort Kopach, Olga
collection PubMed
description Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments.
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spelling pubmed-57964882018-02-14 Nano-engineered microcapsules boost the treatment of persistent pain Kopach, Olga Zheng, Kayiu Dong, Luo Sapelkin, Andrei Voitenko, Nana Sukhorukov, Gleb B. Rusakov, Dmitri A. Drug Deliv Research Article Persistent pain remains a major health issue: common treatments relying on either repeated local injections or systemic drug administration are prone to concomitant side-effects. It is thought that an alternative could be a multifunctional cargo system to deliver medicine to the target site and release it over a prolonged time window. We nano-engineered microcapsules equipped with adjustable cargo release properties and encapsulated the sodium-channel blocker QX-314 using the layer-by-layer (LbL) technology. First, we employed single-cell electrophysiology to establish in vitro that microcapsule application can dampen neuronal excitability in a controlled fashion. Secondly, we used two-photon excitation imaging to monitor and adjust long-lasting release of encapsulated cargo in target tissue in situ. Finally, we explored an established peripheral inflammation model in rodents to find that a single local injection of QX-314-containing microcapsules could provide robust pain relief lasting for over a week. This was accompanied by a recovery of the locomotive deficit and the amelioration of anxiety in animals with persistent inflammation. Post hoc immunohistology confirmed biodegradation of microcapsules over a period of several weeks. The overall remedial effect lasted 10–20 times longer than that of a single focal drug injection. It depended on the QX-314 encapsulation levels, involved TRPV1-channel-dependent cell permeability of QX-314, and showed no detectable side-effects. Our data suggest that nano-engineered encapsulation provides local drug delivery suitable for prolonged pain relief, which could be highly advantageous compared to existing treatments. Taylor & Francis 2018-01-31 /pmc/articles/PMC5796488/ /pubmed/29383961 http://dx.doi.org/10.1080/10717544.2018.1431981 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kopach, Olga
Zheng, Kayiu
Dong, Luo
Sapelkin, Andrei
Voitenko, Nana
Sukhorukov, Gleb B.
Rusakov, Dmitri A.
Nano-engineered microcapsules boost the treatment of persistent pain
title Nano-engineered microcapsules boost the treatment of persistent pain
title_full Nano-engineered microcapsules boost the treatment of persistent pain
title_fullStr Nano-engineered microcapsules boost the treatment of persistent pain
title_full_unstemmed Nano-engineered microcapsules boost the treatment of persistent pain
title_short Nano-engineered microcapsules boost the treatment of persistent pain
title_sort nano-engineered microcapsules boost the treatment of persistent pain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5796488/
https://www.ncbi.nlm.nih.gov/pubmed/29383961
http://dx.doi.org/10.1080/10717544.2018.1431981
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