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Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes
Gene delivery to the cerebral cortex is challenging due to the blood brain barrier and the labile and macromolecular nature of DNA. Here we report gene delivery to the cortex using a glycol chitosan—DNA polyplex (GCP). In vitro, GCPs carrying a reporter plasmid DNA showed approximately 60% of the tr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231247/ https://www.ncbi.nlm.nih.gov/pubmed/35745709 http://dx.doi.org/10.3390/pharmaceutics14061136 |
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author | Petkova, Asya I. Kubajewska, Ilona Vaideanu, Alexandra Schätzlein, Andreas G. Uchegbu, Ijeoma F. |
author_facet | Petkova, Asya I. Kubajewska, Ilona Vaideanu, Alexandra Schätzlein, Andreas G. Uchegbu, Ijeoma F. |
author_sort | Petkova, Asya I. |
collection | PubMed |
description | Gene delivery to the cerebral cortex is challenging due to the blood brain barrier and the labile and macromolecular nature of DNA. Here we report gene delivery to the cortex using a glycol chitosan—DNA polyplex (GCP). In vitro, GCPs carrying a reporter plasmid DNA showed approximately 60% of the transfection efficiency shown by Lipofectamine lipoplexes (LX) in the U87 glioma cell line. Aiming to maximise penetration through the brain extracellular space, GCPs were coated with hyaluronidase (HYD) to form hyaluronidase-coated polyplexes (GCPH). The GCPH formulation retained approximately 50% of the in vitro hyaluronic acid (HA) digestion potential but lost its transfection potential in two-dimensional U87 cell lines. However, intranasally administered GCPH (0.067 mg kg(−1) DNA) showed high levels of gene expression (IVIS imaging of protein expression) in the brain regions. In a separate experiment, involving GCP, LX and naked DNA, the intranasal administration of the GCP formulation (0.2 mg kg(−1) DNA) resulted in protein expression predominantly in the cerebral cortex, while a similar dose of intranasal naked DNA led to protein expression in the cerebellum. Intranasal LX formulations did not show any evidence of protein expression. GCPs may provide a means to target protein expression to the cerebral cortex via the intranasal route. |
format | Online Article Text |
id | pubmed-9231247 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-92312472022-06-25 Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes Petkova, Asya I. Kubajewska, Ilona Vaideanu, Alexandra Schätzlein, Andreas G. Uchegbu, Ijeoma F. Pharmaceutics Article Gene delivery to the cerebral cortex is challenging due to the blood brain barrier and the labile and macromolecular nature of DNA. Here we report gene delivery to the cortex using a glycol chitosan—DNA polyplex (GCP). In vitro, GCPs carrying a reporter plasmid DNA showed approximately 60% of the transfection efficiency shown by Lipofectamine lipoplexes (LX) in the U87 glioma cell line. Aiming to maximise penetration through the brain extracellular space, GCPs were coated with hyaluronidase (HYD) to form hyaluronidase-coated polyplexes (GCPH). The GCPH formulation retained approximately 50% of the in vitro hyaluronic acid (HA) digestion potential but lost its transfection potential in two-dimensional U87 cell lines. However, intranasally administered GCPH (0.067 mg kg(−1) DNA) showed high levels of gene expression (IVIS imaging of protein expression) in the brain regions. In a separate experiment, involving GCP, LX and naked DNA, the intranasal administration of the GCP formulation (0.2 mg kg(−1) DNA) resulted in protein expression predominantly in the cerebral cortex, while a similar dose of intranasal naked DNA led to protein expression in the cerebellum. Intranasal LX formulations did not show any evidence of protein expression. GCPs may provide a means to target protein expression to the cerebral cortex via the intranasal route. MDPI 2022-05-26 /pmc/articles/PMC9231247/ /pubmed/35745709 http://dx.doi.org/10.3390/pharmaceutics14061136 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Petkova, Asya I. Kubajewska, Ilona Vaideanu, Alexandra Schätzlein, Andreas G. Uchegbu, Ijeoma F. Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes |
title | Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes |
title_full | Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes |
title_fullStr | Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes |
title_full_unstemmed | Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes |
title_short | Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes |
title_sort | gene targeting to the cerebral cortex following intranasal administration of polyplexes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231247/ https://www.ncbi.nlm.nih.gov/pubmed/35745709 http://dx.doi.org/10.3390/pharmaceutics14061136 |
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