CONICET | Buscador de Institutos y Recursos Humanos

Self-assembled Lecithin-Biliary Acids based Mixed Micelles for pDNA and siRNA delivery Yamila Gándola1, Sebastián Pérez2, Adriana Carlucci2, Carlos Bregni2, Daniel Turyn1, Lorena González1. 1Departamento de Química Biológica y 2Departamento de Tecnología Farmacéutica; FFyB, UBA, Argentina. The physiological compatibility and the solubilizing capacity that have been recently demonstrated for phosphatidylcholine-bile salts Mixed Micelles (MM), drive to consider them as promising drug delivery systems. Our aim was to study the use of MM for cellular pDNA/siRNA delivery. Designed MM were composed of soy lecithin and Sodium Cholate in different proportions (1:1, 1:2 and 1:4) diluted in water and using pH 5 and pH 7,4 buffers. The MM were characterized in terms of their capability to bind oligonucleotides at different lipid:oligonucleotide (N/P) ratios, their cytotoxicity and delivery efficiency. Binding capability was analyzed by agarose gel EMSA. MTT cell viability assay was used to determined cytotoxicity. Delivery efficiency was assayed by fluorescence microscopy using the pEYFPN1 vector and AlexaFluorRed®-tagged dsRNA in MCF-7 cells. Our results indicated that the MM 1:1 (lecithin: sodium cholate) bind pDNA at N/P ratios 500 and 1000, while the MM 1:2 and 1:4 loaded siRNA at N/P ratios 500 and 1000. Viability assays revealed that the MM prepared in pH 7,4 buffer were cytotoxic, while those pH 5 MM were not cytotoxic for N/P 500 but slightly toxic for N/P 1000. Cytotoxicity of the water MM depends on the proportion lecithin: sodium cholate. The experimental conditions for the MM to deliver the oligonucleotides into the cells were determined by fluorescence microscopy.