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Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes

Petkova, Asya I; Kubajewska, Ilona; Vaideanu, Alexandra; Schätzlein, Andreas G; Uchegbu, Ijeoma F; (2022) Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes. Pharmaceutics , 14 (6) , Article 1136. 10.3390/pharmaceutics14061136. Green open access

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Abstract

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.

Type: Article
Title: Gene Targeting to the Cerebral Cortex Following Intranasal Administration of Polyplexes
Open access status: An open access version is available from UCL Discovery
DOI: 10.3390/pharmaceutics14061136
Publisher version: https://doi.org/10.3390/pharmaceutics14061136
Language: English
Additional information: © 2022 MDPI. This is an open access article distributed under the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Keywords: nose to brain delivery; gene therapy; polyplexes; hyaluronidase; glycol chitosan
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharmaceutics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > Pharma and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10149770
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