title: Adsorption of antisense oligonucleotides targeting malarial topoisomerase II on cationic nanoemulsions optimized by a full factorial design.
abstract: Cationic nanoemulsions have been recently considered as potential delivery systems for oligonucleotides (ON) targeting Plasmodium falciparum topoisomerase II gene. This study is aiming to select the best composition of nanoemulsions intended to ON adsorption by means of a 2(3) full factorial design. Based on their physicochemical properties, two formulations were selected for further studies, both composed by medium chain triglycerides, egg-lecithin, and either oleylamine (OA) or 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP). Adsorption isotherms of phosphodiester or phosphorothioate ON on the optimized nanoemulsions were obtained (ultrafiltration/centrifugation procedure). They showed a significant higher amount of ON adsorbed on DOTAP nanoemulsion when compared to the OA ones. The Langmuir adsorption model provides the most satisfactory representation of the adsorption data. Evidence of ON adsorption could be detected by the inversion of the ζ-potential and the morphology of the oil droplets examined by transmission electron microscopy. Preliminary results regarding hemolytic effect and P. falciparum survival after exposure to optimized formulations were related to their physicochemical properties and in vitro effects. The overall results showed the potential of the optimized nanoemulsions as non-viral carriers for antisense ON against malaria parasites.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Bruxel
authors.forename: Amélie
authors.initials: A
authors.lastname: Bochot
authors.forename: Dirnete
authors.initials: D
authors.lastname: Diel
authors.forename: Luisa
authors.initials: L
authors.lastname: Wild
authors.forename: Edison L S
authors.initials: EL
authors.lastname: Carvalho
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cojean
authors.forename: Philippe M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: Elias
authors.initials: E
authors.lastname: Fattal
authors.affiliation: Faculdade de Farmácia/ UFRGS, Av. Ipiranga, 2752, 90610-000 Porto Alegre, RS, Brazil. helder.teixeira@ufrgs.br.
authors.forename: Helder F
authors.initials: HF
authors.lastname: Teixeira
mesh_terms: D000327:Adsorption; D002412:Cations / Q000737:chemistry / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D015195:Drug Design; D004655:Emulsions; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D013499:Surface Properties
chemical_list: D002412:Cations; D004655:Emulsions; D016376:Oligonucleotides, Antisense; D004250:DNA Topoisomerases, Type II