Journal
PHARMACEUTICAL RESEARCH
Volume 31, Issue 7, Pages 1665-1675Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-013-1271-5
Keywords
cationic lipids; gene therapy; lipoplexes; non-viral vectors; retina
Funding
- University of the Basque Country UPV/EHU [UFI 11/32]
- Research Chair in Retinitis Pigmentosa Bidons Egara
- National Organization of Spanish Blind People (ONCE)
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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. 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. 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. These results hold great expectations for other gene delivery formulations based on this cationic lipid for retinal gene therapy purposes.
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