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A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids
Drug delivery to the brain is highly hindered by the presence of the blood–brain barrier (BBB), which prevents the entry of many potential drugs/biomolecules into the brain. One of the current strategies to achieve gene therapy for neurodegenerative diseases involves direct injection of a viral vect...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407876/ https://www.ncbi.nlm.nih.gov/pubmed/32635142 http://dx.doi.org/10.3390/pharmaceutics12070619 |
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author | Srinageshwar, Bhairavi Florendo, Maria Clark, Brittany Johnson, Kayla Munro, Nikolas Peruzzaro, Sarah Antcliff, Aaron Andrews, Melissa Figacz, Alexander Swanson, Douglas Dunbar, Gary L. Sharma, Ajit Rossignol, Julien |
author_facet | Srinageshwar, Bhairavi Florendo, Maria Clark, Brittany Johnson, Kayla Munro, Nikolas Peruzzaro, Sarah Antcliff, Aaron Andrews, Melissa Figacz, Alexander Swanson, Douglas Dunbar, Gary L. Sharma, Ajit Rossignol, Julien |
author_sort | Srinageshwar, Bhairavi |
collection | PubMed |
description | Drug delivery to the brain is highly hindered by the presence of the blood–brain barrier (BBB), which prevents the entry of many potential drugs/biomolecules into the brain. One of the current strategies to achieve gene therapy for neurodegenerative diseases involves direct injection of a viral vector into the brain. There are various disadvantages of viral vectors, including limitations of cargo size and safety concerns. Nanomolecules, such as dendrimers, serve as an excellent alternative to viral delivery. In this study, as proof-of-concept, we used a surface-modified dendrimer complex and delivered large plasmids to cells in vitro and in vivo in healthy rats via intracranial injection. The dendrimers were biodegradable by chemicals found within cells and toxicity assays revealed that the modified dendrimers were much less toxic than unmodified amine-surface dendrimers. As mentioned in our previous publication, these dendrimers with appropriately modified surfaces are safe, can deliver large plasmids to the brain, and can overcome the cargo size limitations associated with viral vectors. The biocompatibility of this dendritic nanomolecule and the ability to finely tune its surface chemistry provides a gene delivery system that could facilitate future in vivo cellular reprograming and other gene therapies. |
format | Online Article Text |
id | pubmed-7407876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74078762020-08-12 A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids Srinageshwar, Bhairavi Florendo, Maria Clark, Brittany Johnson, Kayla Munro, Nikolas Peruzzaro, Sarah Antcliff, Aaron Andrews, Melissa Figacz, Alexander Swanson, Douglas Dunbar, Gary L. Sharma, Ajit Rossignol, Julien Pharmaceutics Article Drug delivery to the brain is highly hindered by the presence of the blood–brain barrier (BBB), which prevents the entry of many potential drugs/biomolecules into the brain. One of the current strategies to achieve gene therapy for neurodegenerative diseases involves direct injection of a viral vector into the brain. There are various disadvantages of viral vectors, including limitations of cargo size and safety concerns. Nanomolecules, such as dendrimers, serve as an excellent alternative to viral delivery. In this study, as proof-of-concept, we used a surface-modified dendrimer complex and delivered large plasmids to cells in vitro and in vivo in healthy rats via intracranial injection. The dendrimers were biodegradable by chemicals found within cells and toxicity assays revealed that the modified dendrimers were much less toxic than unmodified amine-surface dendrimers. As mentioned in our previous publication, these dendrimers with appropriately modified surfaces are safe, can deliver large plasmids to the brain, and can overcome the cargo size limitations associated with viral vectors. The biocompatibility of this dendritic nanomolecule and the ability to finely tune its surface chemistry provides a gene delivery system that could facilitate future in vivo cellular reprograming and other gene therapies. MDPI 2020-07-03 /pmc/articles/PMC7407876/ /pubmed/32635142 http://dx.doi.org/10.3390/pharmaceutics12070619 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Srinageshwar, Bhairavi Florendo, Maria Clark, Brittany Johnson, Kayla Munro, Nikolas Peruzzaro, Sarah Antcliff, Aaron Andrews, Melissa Figacz, Alexander Swanson, Douglas Dunbar, Gary L. Sharma, Ajit Rossignol, Julien A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids |
title | A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids |
title_full | A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids |
title_fullStr | A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids |
title_full_unstemmed | A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids |
title_short | A Mixed-Surface Polyamidoamine Dendrimer for In Vitro and In Vivo Delivery of Large Plasmids |
title_sort | mixed-surface polyamidoamine dendrimer for in vitro and in vivo delivery of large plasmids |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407876/ https://www.ncbi.nlm.nih.gov/pubmed/32635142 http://dx.doi.org/10.3390/pharmaceutics12070619 |
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