Enhanced Physical Stability of Mixed Ion Pair Amphiphile/Double-chained Cationic Surfactant Vesicles in the Presence of Cholesterol.

In this study, a pseudodouble-chained ion pair amphiphile (IPA), hexadecyltrimethylammoniumdodecylsulfate (HTMA-DS), and dialkyldimethylammonium bromide (DXDAB) with different chain lengths were used as the main materials to fabricate positively charged catanionic vesicles with various mole fractions of cholesterol. The effects of cholesterol and DXDAB alkyl chain length on physical stability of the catanionic vesicles were then investigated by size, zeta potential, and Fourier transform infrared analyses. With the presence of cholesterol in the mixed HTMA-DS/DXDAB vesicles or with increasing the DXDAB content in the presence of a proper amount of cholesterol, the physical stability of the catanionic vesicles could be enhanced. The spacing effect of cholesterol would reduce the counterion binding tendency at the charged vesicle surfaces, resulting in a more pronounced charge character of the catanionic vesicles. Furthermore, cholesterol-induced disordered structure contributed to the flexibility of the vesicular bilayers. Thus the physical stability of the vesicles was improved by adding cholesterol. With increasing the hydrocarbon chain length of DXDAB, cholesterol located toward the middle of the bilayers, enhancing the effects of cholesterol on charge and molecular packing characteristics of the vesicles. This led to a more pronounced stability enhancement effect on the vesicles with a longer alkyl chain length of DXDAB. The results suggested that the presence of cholesterol in the HTMA-DS/DXDAB catanionic vesicles could enhance vesicle stability through adjusting intra-vesicle and/or inter-vesicle interactions. In addition, the stability enhancement effect was more pronounced in the systems with a long DXDAB alkyl chain. The findings will be useful for developing new formulas of catanionic vesicles as drug delivery carriers.