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

作者：Puras Ochoa Gustavo; Zarate Sesma Jon; Agirre Diez Mireia; Diaz Tahoces Ariadna; Aviles Trigeros Marcelino; Grijalvo Santiago; Eritja Ramon; Fernandez Eduardo; Luis Pedraz Jose

来源：Pharmaceutical Research, 2014, 31(7): 1665-1675.

DOI：10.1007/s11095-013-1271-5

• cationic lipids
• gene therapy
• lipoplexes
• non-viral vectors
• retina

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. %26lt;br%26gt;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. %26lt;br%26gt;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. %26lt;br%26gt;These results hold great expectations for other gene delivery formulations based on this cationic lipid for retinal gene therapy purposes.

• 出版日期2014-7