DNA Interaction with Catanionic Vesicles

Abstract

DNA−cationic liposome complexes as possible vehicles for gene delivery is currently an important issue. In this work, the interaction between DNA and thermodynamically stable, spontaneously formed, catanionic vesicles with a net positive charge is studied. A phase map was drawn for the aqueous system of DNA and positively charged vesicles, composed of CTAB (cetyltrimethylammonium bromide) and SOS (sodium octyl sulfate), and showed, as expected, a strong associative phase behavior with the formation of a precipitate. A two-phase region was observed over all the studied concentrations. For DNA−surfactant mixing ratios, [DNA]/[S+] below 1.3 by charge, we found, by optical and electron microscopy, a coexistence between undisturbed vesicles and DNA−surfactant complexes. In samples with a higher excess of DNA, only DNA−vesicle complexes were observed in solution. The structure of these complexes was studied by both small-angle X-ray diffraction (SAXS) and cryogenic transmission electron microscopy (cryo-TEM), and a short-range lamellar structure composed of amphiphile bilayers with DNA molecules ordered and packed between these stacks was found. This type of structure has already been mentioned in the literature as being the most frequently found structure for DNA−liposome mixtures and shows that the vesicles we used, having major advantages with respect to preparation and stability, have similar behavior and can thus be successfully used as model systems. We observed, however, an interesting difference in comparison with previously studied systems. Thus, the addition of DNA in excess to the samples leads not to the coexistence of DNA−vesicle complexes and DNA, as observed before, but to a probable inclusion of DNA in excess in the complexes and therefore to a coexistence of complexes and anionic surfactant micelles expelled from the bilayers.