Title:Adsorption of Antisense Oligonucleotides Targeting Malarial Topoisomerase II on Cationic Nanoemulsions Optimized by a Full Factorial Design
Volume: 14
Issue: 9
Author(s): Fernanda Bruxel, Amélie Bochot, Dirnete Diel, Luisa Wild, Edison L.S. Carvalho, Sandrine Cojean, Philippe M. Loiseau, Elias Fattal and Helder F. Teixeira
Affiliation:
Keywords:
Adsorption isotherms, antisense oligonucleotide, cationic nanoemulsions, factorial design, Plasmodium falciparum
topoisomerase II.
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 23 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.
