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Title

Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes

AuthorsMashal, Mohamed; Attia, Noha; Martínez-Navarrete, Gema; Soto-Sánchez, Cristina; Fernández, Eduardo; Grijalvo, Santiago CSIC ORCID; Eritja Casadellà, Ramón CSIC ORCID ; Puras, Gustavo; Pedraz, Jose Luis
KeywordsChloroquine
Non-viral vectors
Proteins
DNA
Lipids
Issue Date28-Jun-2019
PublisherElsevier
CitationJournal of Controlled Release 304: 181-190 (2019)
AbstractThe incorporation of chloroquine within nano formulations, rather than as a co-treatment of the cells, could open a new avenue for in vivo retinal gene delivery. In this manuscript, we evaluated the incorporation of chloroquine diphosphate into the cationic niosome formulation composed of poloxamer 188, polysorbate 80 non-ionic surfactants, and 2,3-di (tetradecyloxy) propan-1-amine (hydrochloride salt) cationic lipid, to transfect rat retina. Niosome formulations without and with chloroquine diphosphate (DPP80, and DPP80-CQ, respectively) were prepared by the reverse phase evaporation technique and characterized in terms of size, PDI, zeta potential, and morphology. After the incorporation of the pCMS-EGFP plasmid, the resultant nioplexes -at different cationic lipid/DNA mass ratios- were further evaluated to compact, liberate, and secure the DNA against enzymatic digestion. In vitro procedures were achieved in ARPE-19 cells to assess transfection efficacy and intracellular transportation. Both nioplexes formulations transfected efficiently ARPE-19 cells, although the cell viability was clearly better in the case of DPP80-CQ nioplexes. After subretinal and intravitreal injections, DPP80 nioplexes were not able to transfect the rat retina. However, chloroquine containing vector showed protein expression in many retinal cells, depending on the administration route. These data provide new insights for retinal gene delivery based on chloroquine-containing niosome non-viral vectors.
Publisher version (URL)https://doi.org/10.1016/j.jconrel.2019.05.010
URIhttp://hdl.handle.net/10261/181712
DOIhttp://dx.doi.org/10.1016/j.jconrel.2019.05.010
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