Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor
The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration eit...
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| Format: | Online |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921840/ |
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pubmed-49218402016-06-28 Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor Chen, Hong Yang, Georgiana Zong Xin Getachew, Hoheteberhan Acosta, Camilo Sierra Sánchez, Carlos Konofagou, Elisa E. Article The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain. Nature Publishing Group 2016-06-27 /pmc/articles/PMC4921840/ /pubmed/27345430 http://dx.doi.org/10.1038/srep28599 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Chen, Hong Yang, Georgiana Zong Xin Getachew, Hoheteberhan Acosta, Camilo Sierra Sánchez, Carlos Konofagou, Elisa E. |
| spellingShingle |
Chen, Hong Yang, Georgiana Zong Xin Getachew, Hoheteberhan Acosta, Camilo Sierra Sánchez, Carlos Konofagou, Elisa E. Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor |
| author_facet |
Chen, Hong Yang, Georgiana Zong Xin Getachew, Hoheteberhan Acosta, Camilo Sierra Sánchez, Carlos Konofagou, Elisa E. |
| author_sort |
Chen, Hong |
| title |
Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor |
| title_short |
Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor |
| title_full |
Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor |
| title_fullStr |
Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor |
| title_full_unstemmed |
Focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor |
| title_sort |
focused ultrasound-enhanced intranasal brain delivery of brain-derived neurotrophic factor |
| description |
The objective of this study was to unveil the potential mechanism of focused ultrasound (FUS)-enhanced intranasal (IN) brain drug delivery and assess its feasibility in the delivery of therapeutic molecules. Delivery outcomes of fluorescently-labeled dextrans to mouse brains by IN administration either before or after FUS sonication were compared to evaluate whether FUS enhances IN delivery by active pumping or passive diffusion. Fluorescence imaging of brain slices found that IN administration followed by FUS sonication achieved significantly higher delivery than IN administration only, while pre-treatment by FUS sonication followed by IN administration was not significantly different from IN administration only. Brain-derived neurotrophic factor (BDNF), a promising neurotrophic factor for the treatment of many central nervous system diseases, was delivered by IN followed by FUS to demonstrate the feasibility of this technique and compared with the established FUS technique where drugs are injected intravenously. Immunohistochemistry staining of BDNF revealed that FUS-enhanced IN delivery achieved similar locally enhanced delivery as the established FUS technique. This study suggested that FUS enhances IN brain drug delivery by FUS-induced active pumping of the drug and demonstrated that FUS-enhanced IN delivery is a promising technique for noninvasive and localized delivery of therapeutic molecules to the brain. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921840/ |
| _version_ |
1613599911257833472 |