Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

Abstract Extensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal...

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Autores principales:	Paige Smith, Natalia Ogrodnik, Janani Satkunarajah, Meaghan A. O’Reilly
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2e895380f8794339bed8f7db51fecfac
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spelling	oai:doaj.org-article:2e895380f8794339bed8f7db51fecfac2021-12-02T13:19:22ZCharacterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue10.1038/s41598-021-83874-x2045-2322https://doaj.org/article/2e895380f8794339bed8f7db51fecfac2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-83874-xhttps://doaj.org/toc/2045-2322Abstract Extensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.Paige SmithNatalia OgrodnikJanani SatkunarajahMeaghan A. O’ReillyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paige Smith Natalia Ogrodnik Janani Satkunarajah Meaghan A. O’Reilly Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue
description	Abstract Extensive studies on focused ultrasound (FUS)-mediated drug delivery through the blood–brain barrier have been published, yet little work has been published on FUS-mediated drug delivery through the blood-spinal cord barrier (BSCB). This work aims to quantify the delivery of the monoclonal antibody trastuzumab to rat spinal cord tissue and characterize its distribution within a model of leptomeningeal metastases. 10 healthy Sprague–Dawley rats were treated with FUS + trastuzumab and sacrificed at 2-h or 24-h post-FUS. A human IgG ELISA (Abcam) was used to measure trastuzumab concentration and a 12 ± fivefold increase was seen in treated tissue over control tissue at 2 h versus no increase at 24 h. Three athymic nude rats were inoculated with MDA-MB-231-H2N HER2 + breast cancer cells between the meninges in the thoracic region of the spinal cord and treated with FUS + trastuzumab. Immunohistochemistry was performed to visualize trastuzumab delivery, and semi-quantitative analysis revealed similar or more intense staining in tumor tissue compared to healthy tissue suggesting a comparable or greater concentration of trastuzumab was achieved. FUS can increase the permeability of the BSCB, improving drug delivery to specifically targeted regions of healthy and pathologic tissue in the spinal cord. The achieved concentrations within the healthy tissue are comparable to those reported in the brain.
format	article
author	Paige Smith Natalia Ogrodnik Janani Satkunarajah Meaghan A. O’Reilly
author_facet	Paige Smith Natalia Ogrodnik Janani Satkunarajah Meaghan A. O’Reilly
author_sort	Paige Smith
title	Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue
title_short	Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue
title_full	Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue
title_fullStr	Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue
title_full_unstemmed	Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue
title_sort	characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2e895380f8794339bed8f7db51fecfac
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Characterization of ultrasound-mediated delivery of trastuzumab to normal and pathologic spinal cord tissue

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