Exploring physical stability characteristics of positively charged catanionic vesicle/DNA complexes

Abstract

Cationic vesicles fabricated from various novel materials have been recently developed for DNA delivery applications, and the physical stability of the vesicle/DNA complexes played an important role in the transfection efficiency. In this study, positively charged catanionic vesicles composed of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS), ditetradecyldimethylammonium bromide (DTDAB), and cholesterol were prepared in buffer solution by a forced formation approach, and the association behavior of the catanionic vesicles with two types of DNA molecules with the consideration of the vesicle/DNA complex stability was explored by dynamic light scattering, fluorescence polarization, and DNA electrophoresis techniques. In a buffer solution of pH 7.4, HTMA-DS/DTDAB/cholesterol catanionic vesicles with high physical stability and positive charge character were successfully fabricated. A toxicity examination then implied that the catanionic vesicles have the potential of being applied in transfection applications. It is noted that the catanionic vesicle dispersions became unstable as prepared from a concentrated one by dilution due to the less charged vesicle surfaces and the more rigid vesicular bilayers, which could be explained by the enhanced dissolution of HTMA+ from the vesicles. The physical stability and charge character of the catanionic vesicle/DNA complexes were found strongly dependent on the mixing ratio of the vesicle to DNA. The formation of the catanionic vesicle/DNA complexes was also confirmed by an electrophoresis analysis. Moreover, not only the electrostatic repulsion between the vesicle/DNA complexes but also the molecular packing of the vesicular bilayers played roles in governing the physical stability of the vesicle/DNA complexes.