Polycationic amphiphilic cyclodextrin-based nanoparticles for therapeutic gene delivery. (December 2011)

• Record Type: Journal Article
• Authors: Méndez-Ardoy, Alejandro; Urbiola, Koldo; Aranda, Cristina; Ortiz-Mellet, Carmen; García-Fernández, José Manuel; Tros de Ilarduya, Conchita
• Is Part Of: Nanomedicine. Volume 6:Number 10(2011)
• Page Start: 1697
• Page End: 1707
• Publication Date: 2011-12
• Subjects: gene delivery -- gene therapy -- nanotechnology -- pharmaceutical technology -- polycationic amphiphilic cyclodextrins; Nanotechnology -- Periodicals; Medical technology -- Periodicals; Nanotechnology -- Therapeutic use -- Periodicals; 610.28
• DOI: 10.2217/nnm.11.59
• Languages: English
• ISSNs: 1743-5889

Abstract

Aim: In this study, a set of polycationic amphiphilic cyclodextrins featuring self-assembling capabilities in the presence of nucleic acids have been evaluated as therapeutic gene vectors for in vivo purposes.Materials & Methods: A tetradecacationic structure incorporating 14 primary amino groups and 7 thioureido groups in the primary face of the cyclooligosaccharide core and 14 hexanoyl chains in the secondary face was judged to be optimal for therapeutic gene delivery.Results & Conclusion: This compound efficiently mediated serum-resistant transfection in HeLa and HepG2 cells, comparing favorably with branched poly(ethyleneimine), with a low associated toxicity. Further transfection experiments using an encoding therapeutic gene plasmid (pCMVIL-12) were effected to report expression levels of IL-12. Finally, in vivo gene delivery experiments by systemic injection in mice indicated relatively high transfection levels in the liver, overcoming trapping of the nanoparticles in lung cells, with low toxicity.