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

Abstract

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.

Interactions between Cationic Ion Pair Amphiphile Vesicles and Hyaluronan—A Physicochemical Study

“…The preparation of IPA vesicles is described in detail elsewhere. ,,, Briefly, pseudo-double-chained HTMA-DS (IPA) was prepared by mixing 20 mM aqueous solution of two oppositely charged surfactants, HTMAB and SDS, in an equimolar ratio. This mixture was allowed to stand for 1 day for complete precipitation, and the precipitate (IPA) was obtained by filtration (Munktell Filter Paper, Grade 391, 84 g·m –2 , Ahlstrom-Munksjö) and washed with pure water to remove the counterions.…”

“…Ion pair amphiphiles (IPAs) are versatile, easy-to-prepare, and interesting vesicular precursors − prepared by a combination of oppositely charged surfactants. ,, Different combinations of surfactants can result in various vesicles with different properties, such as size, ζ-potential, and polydispersity. Catanionic vesicles have a spherical structure with hydrophilic and hydrophobic domains, and due to this structure, some hydrophilic as well as hydrophobic substances can be encapsulated into these domains.…”

“…A suitable vesicular system was a system based on hexadecyltrimethylammonium-dodecyl sulfate (IPA). Catanionic vesicles prepared only from IPAs usually have very poor physical stability and can easily fuse or aggregate together. ,,− For this reason, the mixture of IPA containing 43 mol % cholesterol was prepared. This amount appears to be the most suitable as the vesicles show high stability .…”

Cholesterol Effect on Membrane Properties of Cationic Ion Pair Amphiphile Vesicles at Different Temperatures

“…Thanks to that, the vesicles gain the same charge and repulsive interactions prevails between them, which results in inhibition of vesicle aggregation. 2,10,13 It is also possible to add cholesterol to the membrane to improve vesicle stability. Cholesterol is an important component of animal cell membranes; its typical concentration is around 20−30 mol % 14,15 and it is widely used as a stabilizing agent in the preparation of vesicles.…”

“…Cholesterol is an important component of animal cell membranes; its typical concentration is around 20−30 mol % 14,15 and it is widely used as a stabilizing agent in the preparation of vesicles. 2,9,14,16 The addition of cholesterol increases the distance between the polar head group of the surfactants forming IPA. This resulted in a shift of the polar group of negatively charged surfactant into the membrane, and the positively charged polar group protruded out of the membrane.…”