Polysorbate 20 non-ionic surfactant enhances retinal gene delivery efficiency of cationic niosomes after intravitreal and subretinal administration

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Graphical abstractThe success of non-viral vectors based on cationic niosomes for retinal gene delivery applications depends on the ability to achieve persistent and high levels of transgene expression, ideally from a single administration. In this work, we studied the effect of the non-ionic surfactant component of niosomes in their transfection efficiency in rat retina. For that purpose, three niosome formulations that only differed in the non-ionic tensioactives were elaborated. Niosomes contained: cationic lipid 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), helper lipid squalene and polysorbate 20, polysorbate 80 or polysorbate 85. Niosomes and corresponding nioplexes were fully characterized in terms of size, polydispersity index, zeta potential, morphology and ability to protect and release DNA. In vitro experiments were carried out to evaluate transfection efficiency, cell viability and intracellular trafficking pathways of the formulations. Nioplexes based on polysorbate 20 niosomes were the most efficient transfecting retinal cells in vitro. Moreover, subretinal and intravitreal administration of those nioplexes in vivo showed also high levels of transgene expression in rat retinas. Our results demonstrate that the incorporation of polysorbate 20 in cationic niosomes enhances retinal gene delivery. Thus, this formulation emerges as a potential non-viral candidate to efficiently transfer specific therapeutic genes into the eye for biomedical purposes.

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