The interaction between the outer layer of a mixed ion pair amphiphile/double-chained cationic surfactant vesicle and DNA: A Langmuir monolayer study

The charge density of vesicular bilayers plays an important role in the structure characteristic of the vesicle-DNA complex for gene delivery. In this work, the charge density effect of catanionic vesicle surfaces on the association behavior of the vesicle with DNA was explored with the model Langmuir monolayer approach. The interaction of negatively charged DNA with positively charged Langmuir monolayers composed of catanionic vesicle-forming materials, hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dihexadecyldimethylammonium bromide (DHDAB), was investigated with surface pressure-area isotherms, area-time relaxation curves and Brewster angle microscope images. The results showed that the adsorption of DNA molecules onto the monolayers was enhanced with an increased DHDAB molar fraction (X _DHDAB), which was apparently related to the increased charge density of the monolayers. With X_DHDAB being increased up to 0.5, the mixed monolayers with a higher X_DHDAB, or higher charge density, possessed a more stable characteristic at high surface pressures, at which the molecular status was close to that in a corresponding vesicular bilayer, due to the DHDAB-improved molecular packing/interaction. It was found that the composition of the mixed HTMA-DS-DHDAB monolayers at high surface pressures would be affected by the adsorbed DNA with the extent depending on X_DHDAB. For the formation of stable HTMA-DS-DHDAB monolayer-DNA complexes, a strong electrostatic interaction of DNA with a monolayer of high charge density and a high monolayer stability characteristic resulting from DHDAB-improved molecular packing/interaction were thus required. The finding has an implication for the formulation of catanionic vesicles composed of an ion pair amphiphile, HTMA-DS, with DHDAB in gene delivery applications.