Catanionic vesicles and DNA complexes: a strategy towards novel gene delivery systems

Abstract

Catanionic vesicles are appealing vectors in non-viral gene transfection. They possess high kinetic stability and the preparation procedures are easy and cheap. In addition, their size and charge are easily modulated by varying the mole ratio between the components. For these reasons, we investigated the interactions between positively charged catanionic vesicles made of didecyldimethylammonium bromide (DiDAB) and 8-hexadecyl sulfate (8-SHS) with calf thymus DNA. Strongly associating complexes are obtained and their structure depends on DNA content. At low concentration, DNA/vesicles complexes are stable, with features very similar to bare vesicles. In the presence of DNA, multi-lamellar entities are formed; the process is promoted by the aggregation and rearrangement of DNA/vesicle complexes. Surface adsorption onto vesicles increases in proportion to DNA content. In such conditions, ζ-potential abruptly decreases, because of the formation of large clusters in which the vesicular identity is retained. Thereafter, precipitation occurs. The solid obtained accordingly is a lamellar phase with DNA sandwiched between the lamellae. The ¹D distance between DNA molecules in the lamellar phase and the precipitate composition depend on the biopolymer content. The double helix of DNA undergoes a reversible compaction process that favors penetration into cells and protects it from nucleases degradation. Finally, addition of the anionic surfactant to the complexes favors DNA release, allowing for a specific signal controlled release.