Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain

Somani, S., Blatchford, D. R., Millington, O., Stevenson, M. L. and Dufès, C. (2014) Transferrin-bearing polypropylenimine dendrimer for targeted gene delivery to the brain. Journal of Controlled Release, 188, pp. 78-86. (doi: 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.<p></p> 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.<p></p> 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 2 h incubation with the treatment.<p></p> 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 24 h following the injection of the treatments.<p></p> These results suggest that transferrin-bearing polypropylenimine dendrimer is a highly promising gene delivery system to the brain.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Millington, Dr Owain and Stevenson, Mrs Lynn
Authors: Somani, S., Blatchford, D. R., Millington, O., Stevenson, M. L., and Dufès, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
Journal Name:Journal of Controlled Release
Publisher:Elsevier B.V.
ISSN:0168-3659
ISSN (Online):1873-4995
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