Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.

Traumatic brain injury (TBI) is an enormous public health problem, with 1.7 million new cases of TBI recorded annually by the Centers for Disease Control. However, TBI has proven to be an extremely challenging condition to treat. Here, we apply a nanoprodrug strategy in a mouse model of TBI. The nov...

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Autores principales:	Morgan A Clond, Bong-Seop Lee, Jeffrey J Yu, Matthew B Singer, Takayuki Amano, Alexander W Lamb, Doniel Drazin, Babak Kateb, Eric J Ley, John S Yu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5d9daee2bbb5491b98b4c71871410dbe
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spelling	oai:doaj.org-article:5d9daee2bbb5491b98b4c71871410dbe2021-11-18T07:48:02ZReactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.1932-620310.1371/journal.pone.0061819https://doaj.org/article/5d9daee2bbb5491b98b4c71871410dbe2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23637912/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Traumatic brain injury (TBI) is an enormous public health problem, with 1.7 million new cases of TBI recorded annually by the Centers for Disease Control. However, TBI has proven to be an extremely challenging condition to treat. Here, we apply a nanoprodrug strategy in a mouse model of TBI. The novel nanoprodrug contains a derivative of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen in an emulsion with the antioxidant α-tocopherol. The ibuprofen derivative, Ibu2TEG, contains a tetra ethylene glycol (TEG) spacer consisting of biodegradable ester bonds. The biodegradable ester bonds ensure that the prodrug molecules break down hydrolytically or enzymatically. The drug is labeled with the fluorescent reporter Cy5.5 using nonbiodegradable bonds to 1-octadecanethiol, allowing us to reliably track its accumulation in the brain after TBI. We delivered a moderate injury using a highly reproducible mouse model of closed-skull controlled cortical impact to the parietal region of the cortex, followed by an injection of the nanoprodrug at a dose of 0.2 mg per mouse. The blood brain barrier is known to exhibit increased permeability at the site of injury. We tested for accumulation of the fluorescent drug particles at the site of injury using confocal and bioluminescence imaging of whole brains and brain slices 36 hours after administration. We demonstrated that the drug does accumulate preferentially in the region of injured tissue, likely due to an enhanced permeability and retention (EPR) phenomenon. The use of a nanoprodrug approach to deliver therapeutics in TBI represents a promising potential therapeutic modality.Morgan A ClondBong-Seop LeeJeffrey J YuMatthew B SingerTakayuki AmanoAlexander W LambDoniel DrazinBabak KatebEric J LeyJohn S YuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61819 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Morgan A Clond Bong-Seop Lee Jeffrey J Yu Matthew B Singer Takayuki Amano Alexander W Lamb Doniel Drazin Babak Kateb Eric J Ley John S Yu Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.
description	Traumatic brain injury (TBI) is an enormous public health problem, with 1.7 million new cases of TBI recorded annually by the Centers for Disease Control. However, TBI has proven to be an extremely challenging condition to treat. Here, we apply a nanoprodrug strategy in a mouse model of TBI. The novel nanoprodrug contains a derivative of the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen in an emulsion with the antioxidant α-tocopherol. The ibuprofen derivative, Ibu2TEG, contains a tetra ethylene glycol (TEG) spacer consisting of biodegradable ester bonds. The biodegradable ester bonds ensure that the prodrug molecules break down hydrolytically or enzymatically. The drug is labeled with the fluorescent reporter Cy5.5 using nonbiodegradable bonds to 1-octadecanethiol, allowing us to reliably track its accumulation in the brain after TBI. We delivered a moderate injury using a highly reproducible mouse model of closed-skull controlled cortical impact to the parietal region of the cortex, followed by an injection of the nanoprodrug at a dose of 0.2 mg per mouse. The blood brain barrier is known to exhibit increased permeability at the site of injury. We tested for accumulation of the fluorescent drug particles at the site of injury using confocal and bioluminescence imaging of whole brains and brain slices 36 hours after administration. We demonstrated that the drug does accumulate preferentially in the region of injured tissue, likely due to an enhanced permeability and retention (EPR) phenomenon. The use of a nanoprodrug approach to deliver therapeutics in TBI represents a promising potential therapeutic modality.
format	article
author	Morgan A Clond Bong-Seop Lee Jeffrey J Yu Matthew B Singer Takayuki Amano Alexander W Lamb Doniel Drazin Babak Kateb Eric J Ley John S Yu
author_facet	Morgan A Clond Bong-Seop Lee Jeffrey J Yu Matthew B Singer Takayuki Amano Alexander W Lamb Doniel Drazin Babak Kateb Eric J Ley John S Yu
author_sort	Morgan A Clond
title	Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.
title_short	Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.
title_full	Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.
title_fullStr	Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.
title_full_unstemmed	Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.
title_sort	reactive oxygen species-activated nanoprodrug of ibuprofen for targeting traumatic brain injury in mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5d9daee2bbb5491b98b4c71871410dbe
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Reactive oxygen species-activated nanoprodrug of Ibuprofen for targeting traumatic brain injury in mice.

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