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Solid lipid nanoparticles as potential tools for gene therapy: In vivo protein expression after intravenous administration

Naked plasmid DNA is a powerful tool for gene therapy, but it is rapidly eliminated from the circulation after intravenous administration. Therefore, the development of optimized DNA delivery systems is necessary for its successful clinical use. Solid lipid nanoparticles (SLNs) have demonstrated tra...

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Bibliographic Details
Published in:International journal of pharmaceutics 2010-01, Vol.385 (1), p.157-162
Main Authors: del Pozo-Rodríguez, Ana, Delgado, Diego, Solinís, Maria Ángeles, Pedraz, Jose Luis, Echevarría, Enrique, Rodríguez, Juan Manuel, Gascón, Alicia R.
Format: Article
Language:English
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Summary:Naked plasmid DNA is a powerful tool for gene therapy, but it is rapidly eliminated from the circulation after intravenous administration. Therefore, the development of optimized DNA delivery systems is necessary for its successful clinical use. Solid lipid nanoparticles (SLNs) have demonstrated transfection capacity in vitro, but their application for gene delivery has not been conveniently investigated in vivo. We aimed to evaluate the capacity of SLN–DNA vectors to transfect in vivo after intravenous administration to mice. The SLNs, composed of Precirol ® ATO 5, DOTAP and Tween 80 were complexed with the plasmid pCMS-EGFP which encodes the enhanced green fluorescent protein (EGFP). The resulting systems were characterized in vitro showing a mean particle size of 276 nm, superficial charge of +28 mV, the ability to protect the plasmid and transfection capacity in culture cells. The intravenous administration in mice led to transfection in hepatic tissue and spleen. Protein expression was detected from the third day after administration, and it was maintained for at least 1 week. This work shows for the first time the capacity of SLN–DNA vectors to induce the expression of a foreign protein after intravenous administration, supporting the potential of SLNs for gene therapy.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2009.10.020