title: The influence of the polar head-group of synthetic cationic lipids on the transfection efficiency mediated by niosomes in rat retina and brain.
abstract: The development of novel non-viral delivery vehicles is essential in the search of more efficient strategies for retina and brain diseases. Herein, optimized niosome formulations prepared by oil-in water (o/w) and film-hydration techniques were characterized in terms of size, PDI, zeta potential, morphology and stability. Three ionizable glycerol-based cationic lipids containing a primary amine group (lipid 1), a triglycine group (lipid 2) and a dimethylamino ethyl pendent group (lipid 3) as polar head-groups were part of such niosomes. Upon the addition of pCMS-EGFP plasmid, nioplexes were obtained at different cationic lipid/DNA ratios (w/w). The resultant nioplexes were further physicochemically characterized and evaluated to condense, release and protect the DNA against enzymatic digestion. In vitro experiments were performed to evaluate transfection efficiency and cell viability in HEK-293, ARPE-19 and PECC cells. Interestingly, niosome formulations based on lipid 3 showed better transfection efficiencies in ARPE-19 and PECC cells than the rest of cationic lipids showed in this study. In vivo experiments in rat retina after intravitreal and subretinal injections together with in rat brain after cerebral cortex administration showed promising transfection efficiencies when niosome formulations based on lipid 3 were used. These results provide new insights for the development of non-viral vectors based on cationic lipids and their applications for efficient delivery of genetic material to the retina and brain.
authors.affiliation: NanoBioCel Group, University of Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Ojeda
authors.affiliation: NanoBioCel Group, University of Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Puras
authors.affiliation: NanoBioCel Group, University of Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Agirre
authors.affiliation: NanoBioCel Group, University of Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Zarate
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Grijalvo
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; Institute of Advanced Chemistry of Catalonia, IQAC-CSIC, Barcelona, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Eritja
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; Neuroprothesis and Neuroengineering Research Group, Miguel Hernández University, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Martinez-Navarrete
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; Neuroprothesis and Neuroengineering Research Group, Miguel Hernández University, Spain.
authors.forename: C
authors.initials: C
authors.lastname: Soto-Sánchez
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; Neuroprothesis and Neuroengineering Research Group, Miguel Hernández University, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Diaz-Tahoces
authors.affiliation: Laboratory of Experimental Ophthalmology, Faculty of Medicine, University of Murcia, Regional Campus of International Excellence "Campus Mare Nostrum", Murcia, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Aviles-Trigueros
authors.affiliation: Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain; Neuroprothesis and Neuroengineering Research Group, Miguel Hernández University, Spain.
authors.forename: E
authors.initials: E
authors.lastname: Fernández
authors.affiliation: NanoBioCel Group, University of Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain. Electronic address: joseluis.pedraz@ehu.es.
authors.forename: J L
authors.initials: JL
authors.lastname: Pedraz
mesh_terms: D000818:Animals; D002412:Cations; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism*; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D004355:Drug Stability; D017930:Genes, Reporter; D005822:Genetic Vectors / Q000008:administration & dosage / Q000737:chemistry*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D056965:Injections, Intraocular; D058449:Intravitreal Injections; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D009474:Neurons / Q000166:cytology; D011412:Propanolamines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology; D014162:Transfection / Q000379:methods*; D014508:Urea / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C000611579:1-(2-dimethylaminoethyl)-3-(2,3-di(tetradecoxy)propyl)urea; D002412:Cations; D008081:Liposomes; D011412:Propanolamines; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D014508:Urea; D004247:DNA
keywords: Brain; Cationic lipid; Gene delivery; Niosomes; Non-viral vector; Retina