Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain
Somani, Sukrut and Blatchford, David R. and Millington, Owain and Stevenson, M. Lynn and Dufès, Christine (2014) Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain. Journal of Controlled Release, 188. pp. 78-86. ISSN 0168-3659 (https://doi.org/10.1016/j.jconrel.2014.06.006)
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Abstract
The possibility of using genes as medicines to treat brain diseases is currently limited by the lack of safe and efficacious delivery systems able to cross the blood-brain barrier, thus resulting in a failure to reach the brain after intravenous administration. On the basis that iron can effectively reach the brain by using transferrin receptors for crossing the blood-brain barrier, we propose to investigate if a transferrin-bearing generation 3-polypropylenimine dendrimer would allow the transport of plasmid DNA to the brain after intravenous administration. In vitro, the conjugation of transferrin to the polypropylenimine dendrimer increased the DNA uptake by bEnd.3 murine brain endothelioma cells overexpressing transferrin receptors, by about 1.4-fold and 2.3-fold compared to that observed with the non-targeted dendriplex and naked DNA. This DNA uptake appeared to be optimal following 2h incubation with the treatment. In vivo, the intravenous injection of transferrin-bearing dendriplex more than doubled the gene expression in the brain compared to the unmodified dendriplex, while decreasing the non-specific gene expression in the lung. Gene expression was at least 3-fold higher in the brain than in any tested peripheral organs and was at its highest 24h following the injection of the treatments. These results suggest that transferrin-bearing polypropylenimine dendrimer is a highly promising gene delivery system to the brain.
ORCID iDs
Somani, Sukrut ORCID: https://orcid.org/0000-0002-0697-1110, Blatchford, David R., Millington, Owain ORCID: https://orcid.org/0000-0002-3026-6550, Stevenson, M. Lynn and Dufès, Christine ORCID: https://orcid.org/0000-0002-7963-6364;-
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Item type: Article ID code: 48517 Dates: DateEvent28 August 2014Published14 June 2014Published Online5 June 2014AcceptedSubjects: Medicine > Pharmacy and materia medica
Medicine > Therapeutics. PharmacologyDepartment: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Technology and Innovation Centre > BionanotechnologyDepositing user: Pure Administrator Date deposited: 13 Jun 2014 09:32 Last modified: 20 Dec 2024 01:21 URI: https://strathprints.strath.ac.uk/id/eprint/48517