Sphingolipid extracts enhance gene delivery of cationic lipid vesicles into retina and brain
| Autor: | José Luis Pedraz, Eduardo Fernández, Gema Martínez-Navarrete, Myriam Sainz-Ramos, Gustavo Puras, Nuseibah Al Qtaish, Patricia Gálvez Martín, Tania Belen Lopez-Mendez, Cristina Soto-Sánchez, Ilia Villate-Beitia, Idoia Gallego |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
retina
Cell Survival brain Genetic Vectors Pharmaceutical Science Retinal Pigment Epithelium Complex Mixtures Gene delivery Endocytosis Mice Caveolae medicine Animals Humans Viability assay Niosome Retina sphingolipids Chemistry Gene Transfer Techniques niosomes Genetic Therapy General Medicine Transfection niosphingosomes Sphingolipid gene therapy Cell biology medicine.anatomical_structure Liposomes Emulsions Plasmids Biotechnology |
| Zdroj: | Addi. Archivo Digital para la Docencia y la Investigación instname |
| Popis: | [EN]The aim was to evaluate relevant biophysic processes related to the physicochemical features and gene transfection mechanism when sphingolipids are incorporated into a cationic niosome formulation for non-viral gene delivery to central nervous system. For that, two formulations named niosphingosomes and niosomes devoid of sphingolipid extracts, as control, were developed by the oil-in water emulsion technique. Both formulations and the corresponding complexes, obtained upon the addition of the reporter EGFP plasmid, were physicochemically and biologically characterized and evaluated. Compared to niosomes, niosphingosomes, and the corresponding complexes decreased particle size and increased superficial charge. Although there were not significant differences in the cellular uptake, cell viability and transfection efficiency increased when human retinal pigment epithelial (ARPE-19) cells were exposed to niosphingoplexes. Endocytosis via caveolae decreased in the case of niosphingoplexes, which showed higher co-localization with lysosomal compartment, and endosomal escape properties. Moreover, niosphingoplexes transfected not only primary central nervous system cells, but also different cells in mouse retina, depending on the administration route, and brain cortex. These preliminary results suggest that niosphingosomes represent a promising non-viral vector formulation purposed for the treatment of both retinal and brain diseases by gene therapy approach. This work was supported by the Basque Country Government (Department of Education, University and Research, Consolidated Groups IT907-16) . Additional funding was provided by the CIBER of Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) , an initiative of the Carlos III Health Institute (ISCIII) . I.V.B. and M.S.R. thank the University of the Basque Country (UPV/EHU) for the granted postdoctoral fellowship (ESPDOC19/47) and the granted pre-doctoral fellowship (PIF17/79) , respectively. Authors wish to thank the intel-lectual and technical assistance from the ICTS "NANBIOSIS," more specifically by the Drug Formulation Unit (U10) of the CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the University of Basque Country (UPV/EHU) . Technical and human sup-port provided by SGIKER (UPV/EHU) is also gratefully acknowledged. |
| Databáze: | OpenAIRE |
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