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A Novel Formulation Based on 2,3-Di(tetradecyloxy)propan-1-amine Cationic Lipid Combined with Polysorbate 80 for Efficient Gene Delivery to the Retina

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ABSTRACT

Purpose

The aim of the present study was to evaluate the potential application of a novel formulation based on a synthesized cationic lipid 2,3-di(tetradecyloxy)propan-1-amine, combined with polysorbate 80 to deliver the pCMS-EGFP plasmid into the rat retina.

Methods

We elaborated lipoplexes by mixing the formulation containing the cationic lipid and the polysorbate 80 with the plasmid at different cationic lipid/DNA ratios (w/w). Resulted lipoplexes were characterized in terms of size, charge, and capacity to condense, protect and release the DNA. In vitro transfection studies were performed in HEK-293 and ARPE-19 cells. Formulations were also tested in vivo by monitoring the expression of the EGFP after intravitreal and subretinal injections in rat eyes.

Results

At 2/1 cationic lipid/DNA mass ratio, the resulted lipoplexes had 200 nm of hydrodynamic diameter; were positive charged, spherical, protected DNA against enzymatic digestion and transfected efficiently HEK-293 and ARPE-19 cultured cells exhibiting lower cytotoxicity than LipofectamineTM 2000. Subretinal administrations transfected mainly photoreceptors and retinal pigment epithelial cells; whereas intravitreal injections produced a more uniform distribution of transfection through the inner part of the retina.

Conclusions

These results hold great expectations for other gene delivery formulations based on this cationic lipid for retinal gene therapy purposes.

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ACKNOWLEDGMENTS AND DISCLOSURES

This project was partially supported by the University of the Basque Country UPV/EHU (UFI 11/32), by the Research Chair in Retinitis Pigmentosa ¨Bidons Egara¨, and by the National Organization of Spanish Blind People (ONCE). Technical and human support provided by SGIker (UPV/EHU) is gratefully acknowledged.

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Authors and Affiliations

  1. University of the Basque Country, Vitoria, Spain

    Gustavo Puras Ochoa, Jon Zárate Sesma, Mireia Agirre Díez, Ariadna Díaz-Tahoces, Marcelino Avilés-Trigeros, Santiago Grijalvo, Ramón Eritja, Eduardo Fernández & Jose Luis Pedraz

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  1. Gustavo Puras Ochoa
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  2. Jon Zárate Sesma
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Correspondence to Jose Luis Pedraz.

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Ochoa, G.P., Sesma, J.Z., Díez, M.A. et al. A Novel Formulation Based on 2,3-Di(tetradecyloxy)propan-1-amine Cationic Lipid Combined with Polysorbate 80 for Efficient Gene Delivery to the Retina. Pharm Res 31, 1665–1675 (2014). https://doi.org/10.1007/s11095-013-1271-5

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  • DOI: https://doi.org/10.1007/s11095-013-1271-5

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