Cargando…

Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents

Severe traumatic brain injury (TBI), such as that suffered by patients with cerebral contusion, is a major cause of death and disability in young persons. Effective therapeutics to treat or mitigate the effects of severe TBI are lacking, in part because drug delivery to the injured brain remains a c...

Descripción completa

Detalles Bibliográficos
Autores principales: Whitener, Ricky, Henchir, Jeremy J., Miller, Thomas A., Levy, Emily, Krysiewicz-Bell, Aubrienne, Abrams, Eliza S. LaRovere, Carlson, Shaun W., Menon, Naresh, Dixon, C. Edward, Whalen, Michael J., Rogers, Claude J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Mary Ann Liebert, Inc., publishers 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985535/
https://www.ncbi.nlm.nih.gov/pubmed/35403102
http://dx.doi.org/10.1089/neur.2021.0049
_version_ 1784682381719896064
author Whitener, Ricky
Henchir, Jeremy J.
Miller, Thomas A.
Levy, Emily
Krysiewicz-Bell, Aubrienne
Abrams, Eliza S. LaRovere
Carlson, Shaun W.
Menon, Naresh
Dixon, C. Edward
Whalen, Michael J.
Rogers, Claude J.
author_facet Whitener, Ricky
Henchir, Jeremy J.
Miller, Thomas A.
Levy, Emily
Krysiewicz-Bell, Aubrienne
Abrams, Eliza S. LaRovere
Carlson, Shaun W.
Menon, Naresh
Dixon, C. Edward
Whalen, Michael J.
Rogers, Claude J.
author_sort Whitener, Ricky
collection PubMed
description Severe traumatic brain injury (TBI), such as that suffered by patients with cerebral contusion, is a major cause of death and disability in young persons. Effective therapeutics to treat or mitigate the effects of severe TBI are lacking, in part because drug delivery to the injured brain remains a challenge. Promising therapeutics targeting secondary injury mechanisms may have poor pharmacokinetics/pharmacodynamics, unwanted side effects, or high hydrophobicity. To address these challenges, we have developed a multi-lamellar vesicle nanoparticle (MLV-NP) formulation with a narrow size distribution (243 nm in diameter, 0.09 polydispersity index) and the capability of encapsulating hydrophobic small molecule drugs for delivery to the injured brain. To demonstrate the utility of these particles, we produced dual-fluorescent labeled nanoparticles containing the organic dyes, coumarin 153 and rhodamine B, that were delivered intravenously to Sprague-Dawley rats and C57Bl6/J mice at 1, 1 and 4, 24, or 48 h after controlled cortical impact injury. Distribution of particles was measured at 5, 25, 48, or 49 h post-injury by fluorescence microscopy of coronal brain sections. In all cases of MLV administration, a 1.2- to 1.9-fold enhancement of ipsilateral fluorescence signal was observed compared to the contralateral cortex. Enhanced fluorescence was also observed in the injured hippocampal tissue in these animals. MLV-NPs administered at 1 h were observed intracellularly in the injured hemisphere at 48 h, suggesting the possibility of concentrated drug delivery to injured cells. These results suggest that MLV-NP delivery of therapeutic agents may be a viable strategy for treating cerebral contusion TBI.
format Online
Article
Text
id pubmed-8985535
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Mary Ann Liebert, Inc., publishers
record_format MEDLINE/PubMed
spelling pubmed-89855352022-04-07 Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents Whitener, Ricky Henchir, Jeremy J. Miller, Thomas A. Levy, Emily Krysiewicz-Bell, Aubrienne Abrams, Eliza S. LaRovere Carlson, Shaun W. Menon, Naresh Dixon, C. Edward Whalen, Michael J. Rogers, Claude J. Neurotrauma Rep Original Article Severe traumatic brain injury (TBI), such as that suffered by patients with cerebral contusion, is a major cause of death and disability in young persons. Effective therapeutics to treat or mitigate the effects of severe TBI are lacking, in part because drug delivery to the injured brain remains a challenge. Promising therapeutics targeting secondary injury mechanisms may have poor pharmacokinetics/pharmacodynamics, unwanted side effects, or high hydrophobicity. To address these challenges, we have developed a multi-lamellar vesicle nanoparticle (MLV-NP) formulation with a narrow size distribution (243 nm in diameter, 0.09 polydispersity index) and the capability of encapsulating hydrophobic small molecule drugs for delivery to the injured brain. To demonstrate the utility of these particles, we produced dual-fluorescent labeled nanoparticles containing the organic dyes, coumarin 153 and rhodamine B, that were delivered intravenously to Sprague-Dawley rats and C57Bl6/J mice at 1, 1 and 4, 24, or 48 h after controlled cortical impact injury. Distribution of particles was measured at 5, 25, 48, or 49 h post-injury by fluorescence microscopy of coronal brain sections. In all cases of MLV administration, a 1.2- to 1.9-fold enhancement of ipsilateral fluorescence signal was observed compared to the contralateral cortex. Enhanced fluorescence was also observed in the injured hippocampal tissue in these animals. MLV-NPs administered at 1 h were observed intracellularly in the injured hemisphere at 48 h, suggesting the possibility of concentrated drug delivery to injured cells. These results suggest that MLV-NP delivery of therapeutic agents may be a viable strategy for treating cerebral contusion TBI. Mary Ann Liebert, Inc., publishers 2022-04-05 /pmc/articles/PMC8985535/ /pubmed/35403102 http://dx.doi.org/10.1089/neur.2021.0049 Text en © Ricky Whitener et al., 2022; Published by Mary Ann Liebert, Inc. https://creativecommons.org/licenses/by/4.0/This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Whitener, Ricky
Henchir, Jeremy J.
Miller, Thomas A.
Levy, Emily
Krysiewicz-Bell, Aubrienne
Abrams, Eliza S. LaRovere
Carlson, Shaun W.
Menon, Naresh
Dixon, C. Edward
Whalen, Michael J.
Rogers, Claude J.
Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents
title Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents
title_full Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents
title_fullStr Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents
title_full_unstemmed Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents
title_short Localization of Multi-Lamellar Vesicle Nanoparticles to Injured Brain Tissue in a Controlled Cortical Impact Injury Model of Traumatic Brain Injury in Rodents
title_sort localization of multi-lamellar vesicle nanoparticles to injured brain tissue in a controlled cortical impact injury model of traumatic brain injury in rodents
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985535/
https://www.ncbi.nlm.nih.gov/pubmed/35403102
http://dx.doi.org/10.1089/neur.2021.0049
work_keys_str_mv AT whitenerricky localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT henchirjeremyj localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT millerthomasa localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT levyemily localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT krysiewiczbellaubrienne localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT abramselizaslarovere localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT carlsonshaunw localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT menonnaresh localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT dixoncedward localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT whalenmichaelj localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents
AT rogersclaudej localizationofmultilamellarvesiclenanoparticlestoinjuredbraintissueinacontrolledcorticalimpactinjurymodeloftraumaticbraininjuryinrodents