Salt Effect on the Aggregation Behaviors of an Anionic Carboxylate Gemini and a Cationic Surfactant

The synthesis method and conditions for the carboxylate Gemini surfactant O,O′‐bis(sodium 2‐lauricate)‐p‐benzenediol (C₁₁pPHCNa) were explored. Surface tension data of the single and mixed systems of catanionic (cationic with anionic) surfactants with different salt concentrations were used to determine the CMC values and to obtain the information of self‐assembly behaviors of the surfactants. Aggregates' morphologies were observed by transmission electron microscopy (TEM) and speculation was made according to the viscosity measurement results. The results show that large spherical aggregates formed in the mixed solution, which tend to transfer into branched and wormlike mixed micelles with the increases of the salt concentration. The viscosity of the mixed solution was found to increase gradually corresponding to the change of the catanionic surfactant mixtures' morphology.     

Versatility of cyclodextrins in self-assembly systems of amphiphiles

Recently, cyclodextrins (CDs) were found to play important yet complicated (or even apparently opposite sometimes) roles in self-assembly systems of amphiphiles or surfactants. Herein, we try to review and clarify the versatility of CDs in surfactant assembly systems by 1) classifying the roles played by CDs into two groups (modulator and building unit) and four subgroups (destructive and constructive modulators, amphiphilic and unamphiphilic building units), 2) comparing these subgroups, and 3) analyzing mechanisms. As a modulator, although CDs by themselves do not participate into the final surfactant aggregates, they can greatly affect the aggregates in two ways. In most cases CDs will destroy the aggregates by depleting surfactant molecules from the aggregates (destructive), or in certain cases CDs can promote the aggregates to grow by selectively removing the less-aggregatable surfactant molecules from the aggregates (constructive). As an amphiphilic building unit, CDs can be chemically (by chemical bonds) or physically (by host–guest interaction) attached to a hydrophobic moiety, and the resultant compounds act as classic amphiphiles. As an unamphiphilic building unit, CD/surfactant complexes or even CDs on their own can assemble into aggregates in an unconventional, unamphiphilic manner driven by CD–CD H-bonds. Moreover, special emphasis is put on two recently appeared aspects: the constructive modulator and unamphiphilic building unit.     

Hydrogenated/fluorinated catanionic surfactants as potential templates for nanostructure design

The structure and physicochemical properties of the nanoparticles spontaneously formed within aqueous mixtures of the hydrogenated/fluorinated catanionic surfactant cetyltrimetylammonium perfluorooctanoate in the absence of counterions as a function of its concentration are investigated by a combined experimental/computational study at room temperature. Apparent molar volumes, isentropic apparent molar compressibilities, and dynamic light scattering measurements together with transmission and cryo-scanning electron as well as confocal laser microscopy images, and computational molecular dynamics simulations indicate that a variety of structures of different sizes coexist in solution with vesicles of ～160 nm diameter. Interestingly, the obtained nanostructures were observed to self-assemble from a random distribution of monomers in a time scale easily accessible by atomistic classical molecular dynamics simulations, allowing to provide a comprehensive structural and dynamic characterization of the surfactant molecules at atomic level within the different aggregates. Overall, it is demonstrated that the use of mixed fluorinated hydrogenated surfactant systems represents an easy strategy for the design of specific nanoscale structures. The detailed structural analysis provided in the present work is expected to be useful as a reference to guide the design of new nanoparticles based on different hydrogenated/fluorinated catanionic surfactants.     

Unusual vesicle-micelle transitions in a salt-free catanionic surfactant: temperature and concentration effects

The spontaneous formation of vesicles by the salt-free surfactant hexadecyltrimethylammonium octylsulfonate (TASo) and the features of an unusual vesicle-micelle transition are investigated in this work. In a previous work, we have shown that this highly asymmetric catanionic surfactant displays a rare lamellar miscibility gap in the concentrated regime. Here, we analyze in detail the aggregation behavior in the dilute regime (less than 3 wt % surfactant) as a function of both concentration and temperature. The phase diagram is dominated by a two-phase region consisting of a dispersion of a swollen lamellar phase (Lalpha') in the excess solvent phase (L1). Stable vesicles form in this two-phase region, and upon temperature increase, a transition to a single solution phase containing only elongated micelles occurs. The structural characterization of the aggregates and the investigation of their equilibrium properties have been carried out by light microscopy, cryo-TEM, water self-diffusion NMR, and SANS. Similarly to the lamellar-lamellar coexistence, the changes in microstructure at high dilution and high temperature can be understood from solubility differences, electrostatic interactions, and preferred aggregate curvature. Surface charge in the aggregates stems from the higher solubility of the octylsulfonate (So-) ion as compared to that of the hexadecyltrimethylammonium ion (TA+). Upon temperature increase, the ratio of free So(-) relative to the neutral TASo increases. Consequently, the surface charge density of the aggregates increases, and this ultimately induces a transition to a higher-curvature morphology (elongated micelles). Vesicles can also be spontaneously formed by cooling solutions from the micellar region, and the mean size obtained is practically independent of cooling rate, suggesting that dissociation/charge effects also control this process.     

Effect of alkyl chain asymmetry on catanionic mixtures of hydrogenated and fluorinated surfactants

In this work we studied and compared the physicochemical properties of the catanionic mixtures cetyltrimethyl-ammonium bromide–sodium dodecanoate, cetyltrimethyl-ammonium bromide–sodium perfluorodacanoate, octyltrimethylammonium bromide–sodium perfluorodacanoate and cetyltrimethyl-ammonium bromide–sodium octanoate by a combination of rheological, transmission electron microscopy (TEM) and polarized optical microscopy measurements. The binary mixtures of the surfactants have been analyzed at different mixed ratios and total concentration of the mixture. Mixtures containing a perfluorinated surfactant are able to form lamellar liquid crystals and stable spontaneous vesicles. Meanwhile, system containing just hydrogenated surfactants form hexagonal phases or they are arranged in elongated aggregates.     

Synergism and polymorphism in mixed surfactant systems

Mixed surfactant systems have been, for a long time, one of the favorite areas for experimental studies on interfacial and bulk properties of surfactants. Beyond the well-known synergistic properties, with relevance to technical applications, recent studies increasingly focus on the bulk aggregation behavior. As more systematic and detailed experimental data is collected (for example, by use of scattering and direct imaging techniques), increasingly refined theoretical models are developed. Most references reviewed here clearly show both the trends. Topics such as micellar growth, micelle-to-vesicle transition and equilibrium vesicle formation in dilute systems (in particular in catanionic systems) continue to expand and sometimes pose challenges to conventional notions of surfactant self-organization. As the rich polymorphism of mixed aggregates is unraveled, the possibilities of using them for broader goals also increase (e.g. mesoporous materials and polymer-aggregate gels).     

An Assessment of the Aggregation and Adsorption Behavior of the Sodium Dodecylsulfate–Cetyltrimethylammonium Bromide Mixed Surfactant System in Aqueous Medium

Sodium dodecylsulfate and cetyltrimethylammonium bromide mixtures are important catanionic systems, as they have an inherent tendency to form vesicle structures. Despite extensive studies on the phase behavior and microstructures, there is dearth of basic information on the aggregation and adsorption behavior of this mixed system. In this work the critical micelle concentration, surface tension reduction effectiveness, surface excess, mixed micelle and monolayer compositions, activity coefficients, interaction parameters, counterion binding and Gibbs energy terms of this mixed system are determined by measuring its surface tension and conductance as a function of composition. The dependence of mixed micelle composition on surfactant concentration has been successfully demonstrated.     

The effect of double-chain surfactants on armored bubbles: a surfactant-controlled route to colloidosomes

We find that the gas phases of air bubbles covered with anionic or cationic polystyrene latex particles dissolve on exposure to cationic and catanionic surfactants. The particles on the bubble interface are released as singlets or aggregates when the surfactant has a single hydrophobic chain, while porous colloidal capsules (colloidosomes) with the same aqueous phase inside as out are obtained when the surfactant has two hydrophobic chains. The formation of colloidosomes from the particle-covered bubbles does not appear to depend significantly on the charge of the particles, which makes it unlikely that bilayers of surfactant are stabilizing the colloidosome. While the exact mechanism of formation remains an open question, our method is a simple one-step process for obtaining colloidosomes from particle-covered bubbles.     

Phase behavior in mixtures of cationic and anionic surfactants in aqueous solutions

Phase behavior of cationic/anionic surfactant mixtures of the same chain length (n=10, 12 or 14) strongly depends on the molar ratio and actual concentration of the surfactants. Precipitation of catanionic surfactant and mixed micelles formation are observed over the concentration range investigated. Coacervate and liquid crystals are found to coexist in the transition region from crystalline catanionic surfactant to mixed micelles.The addition of oppositely charged surfactant diminishes the surface charge density at the mixed micelle/solution interface and enhances the apparent degree of counterion dissociation from mixed micelles. Cationic surfactants have a greater tendency to be incorporated in mixed micelles than anionic ones.     

Optical spectroscopic and TEM studies of catanionic micelles of CTAB/SDS and their interaction with a NSAID

If a vesicle is a better model of a membrane in the context of the hydrophobic effect, then from the charge distribution point of view, a catanionic micelle is a closer model to a biomembrane. We have prepared and characterized two different types of catanionic micelles of sodium dodecyl sulfate (SDS) and cetyl N,N,N-trimethylammonium bromide (CTAB) having different surface charge ratios using optical spectroscopy and transmission electron microscopy. The average size of both types of mixed micelles was found to be much larger than that of micelles containing uniformly charged headgroups. Catanionic micelles containing higher concentrations of positively charged headgroups (CTAB) are larger in size, less compact, and more polar compared to the micelles containing higher concentrations of negatively charged headgroups (SDS). We have used these catanionic micelles as membrane mimetic systems to understand the interaction of piroxicam, a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam group, with biomembranes. In continuation of our work on membrane mimetic systems, we have used spectral properties of the drug itself to understand the effect of the presence of mixed charges on the micellar surface in guiding the interaction of catanionic micelles with piroxicam. Our earlier studies of the interaction of piroxicam with micelles having uniform surface charges have shown that the charge on the micellar surface not only dictates which prototropic form of the drug will be incorporated in the micelles but also induces a switch-over between different prototropic forms of piroxicam. The equilibrium of this switch-over is extremely sensitive to the environment. In this study, we demonstrate how even small changes in the electrostatic forces obtained by doping the uniformly charged surface of the micelles with oppositely charged headgroups (as in catanionic micelles) are capable of fine-tuning this equilibrium. This implies that the surface charge of biomembranes, which are quite diverse in vivo, might play a significant role in selecting a particular form of the drug to be presented to its targets.     

Cytotoxicity characterization of catanionic vesicles in RAW 264.7 murine macrophage-like cells

In comparison with cationic liposomes, catanionic vesicles possess more attractive properties such as stability and lower cost, and these characteristics may make them suitable as a non-viral vehicle and for other biomedical applications such as vaccine adjuvants. However, very little is known about their possible cytotoxic mechanisms in cellular system. Also, this information is vital for the future development of safe biomedical systems. In the current study, the cytotoxic effect of catanionic vesicles, consisting of anionic surfactant (SDS), cationic surfactant (HTMAB), and cholesterol, in cultured RAW 264.7 murine macrophage-like cells was determined. The treatment of catanionic vesicles produced a dose-dependent effect on macrophage cells. RAW 264.7 cells exposed to catanionic vesicles exhibited morphological features of apoptosis such as chromatin condensation. Typical apoptotic ladders were observed in DNA extracted from RAW 264.7 cells treated by catanionic vesicles. Analysis from flow cytometry demonstrated an increase of hypodiploid DNA population (sub-G1) and a simultaneous decrease of diploid DNA content, indicating that DNA cleavage occurred after exposure of the cells with catanionic vesicles. In addition, it was shown that pretreatment of RAW 264.7 cells with the general caspase inhibitor (zVAD-fmk) did not prevent apoptosis induced by catanionic vesicles, suggesting that apoptosis in macrophage cells followed a caspase-independent pathway induced by catanionic vesicles. These data provide novel insight into the effect of catanionic vesicles on the mechanisms of cell death induced by catanionic vesicles.     

Properties of the amphiphilic films in mixed cationic/anionic vesicles: a comprehensive view from a literature analysis

The so-called 'catanionic' vesicles are made from mixtures of cationic and anionic surfactants. They are attracting much interest because they form spontaneously and they can be obtained from a variety of surfactants, either commercially available or issued from original synthesis. A distinction can be made between the properties of simple surfactant mixtures and of ion pair amphiphiles (IPA), in which the counterions have been removed. We have drawn up in this paper, an inventory of the different vesicular systems which have been described in the literature, insisting on the specific features associated with these two categories of systems. We have collected here especially, information concerning the phase behaviors, the microscopic composition of the vesicular particles, their structural and size determinations, the dynamic aspects (including the micelle-vesicle transition), the theoretical predictions from thermodynamic models and the entrapment of probe molecules. We discuss the potential of catanionic vesicles as delivery systems and we show that a full understanding of their entrapment/release properties will call for much more experimental work with well defined protocols. We also point out some unsolved questions concerning the role of the excess surfactant in the stabilization of the particles and the conditions required to obtain a favourable curvature of the surfactant film.     

Phase behavior and rheological properties of salt-free catanionic TTAOH/DA/H2O system in the presence of hydrophilic and hydrophobic salts

In the cationic and anionic (catanionic) surfactant mixed system, tetradecyltrimethylammonium hydroxide (TTAOH)/decanoic acid (DA)/H(2)O, abundant phase behaviors were obtained in the presence of hydrophilic and hydrophobic salts. The microstructures of typical L(α) phases with the different compositions were characterized by the transmission electron microscope (TEM) images. Aqueous double-phase transition induced by addition of hydrophilic salts was observed when the cationic surfactant was in excess. Salt-induced reversible vesicle phases could be obtained when the anionic surfactant was excess, whereas the vesicle phase at lower salinity behaves highly viscoelastic but is much less viscoelastic with high salinity which was demonstrated by measuring their rheological properties. The L(α) phase with the positive membrane charges can be finally transferred into an L(1) phase with added salts. The ion specificity of hydrophilic and hydrophobic salts is discussed, and the order of cations is summarized, which is significant for the further study of the Hofmeister effects on catanionic surfactant mixed systems.     

Determining the cytotoxicity of catanionic surfactant mixtures on HeLa cells

The cytotoxicity of commonly used synthetic surfactants and catanionic mixtures of those was evaluated using MTT on HeLa cells. The 50% inhibition concentration (IC₅₀) for MTT reduction was calculated. The effect on chain length increase and inclusion of polyoxyethylene groups on the toxicity was tested on single surfactant systems. A general trend of increasing toxicity with increasing chain length and the presence of polyoxyethylene groups was observed. The measured IC₅₀ values of catanionic systems lie between those of participating surfactants. The increase in toxicity as the cationic surfactant is added to the anionic one is however not linear. A steep decrease of the IC₅₀ values (and therefore increase in the toxic properties) is observed immediately already at low concentrations of the cationic surfactants. This behavior is analogous to the enzyme activity in catanionic microemulsions.     

Temperature-induced vesicle aggregation in catanionic surfactant systems: the effects of the headgroup and counterion

The peculiar nature of temperature-induced vesicle aggregation (TIVA) in some catanionic surfactant systems is systematically investigated. On the basis of a general analysis of the intervesicular interactions, the main driving force for this phenomenon is considered to be the intervesicular hydrophobic interaction among the exposed hydrophobic part of the surfactant headgroups. The addition of an oppositely charged hydrophobic salt to the catanionic vesicle systems is also found to promote the occurrence of TIVA. In fact, TIVA can be induced in ordinary catanionic vesicle systems by the addition of an oppositely charged hydrophobic counterion.     

Electrolyte effect on adsorption and the phase transition from microstructures to nanostructures in ionic/ionic surfactants mixture

The effect of salt concentration on intermicellar interactions and aggregate structures of anionic and cationic-rich mixtures of CTAB (cetyltrimethylammonium bromide) and SDS (sodium dodecyl sulfate) were investigated with conductometry, surface tension, zeta potential, cyclic voltammetry measurements and by determining the surfactant NMR self-diffusion coefficients. The critical aggregate concentration (CAC), surface excess (Γ(max)), and mean molecular surface area (A(min)) were determined from plots of the surface tension (γ) as a function of the log of total surfactant concentration. The electrochemical behavior of cationic-anionic (catanionic) mixed surfactant and self-assembled surfactant monomers at Pt wire electrode were studied by cyclic voltammetry (CV). A variation in the peak current versus the total concentration of surfactant allow us to evaluate the CAC and related parameters from regular solution theory along with the diffusion coefficient of the electroactive species. It was observed that, for both the planar air/aqueous interface and micellar systems, the nonideality decreased as the amount of electrolyte in the aqueous medium was increased. Finally, we investigated the variations of electrostatic, transfer and steric free energy in phase transition between mixed micelle and vesicle in the presence of electrolyte using the presented model by our groups.     

Aggregation behavior of p-n-alkylbenzamidinium chloride surfactants

The aggregation behavior of a novel class of surfactants, p-n-alkylbenzamidinium chlorides, has been investigated. The thermodynamics of aggregation of p-n-decylbenzamidinium chloride mixed with cationic and anionic cosurfactants has been studied using isothermal titration calorimetry. For mixtures of p-n-decylbenzamidinium chloride with n-alkyltrimethylammonium chlorides, the aggregation process is enthalpically more favorable than for the pure n-alkyltrimethylammonium chlorides, probably caused by diminished headgroup repulsion due to charge delocalization in the amidinium headgroup. A critical aggregation concentration between 3 and 4 mM has been extrapolated for p-n-decylbenzamidinium chloride at 40 degrees C, around two times lower than that of similar surfactants without charge delocalization in the headgroup and well comparable to that of similar surfactants with charge delocalization in the headgroup. In mixtures of p-n-decylbenzamidinium chloride with either sodium n-alkylsulfates or sodium dodecylbenzenesulfonate, evidence is found for the formation of bilayer aggregates by the pseudo-double-tailed catanionic surfactants composed of p-n-decylbenzamidinium and the anionic surfactant. These aggregates are solubilized to mixed micelles by excess free anionic surfactant at the measured critical aggregation concentration.     

DNA encapsulation by biocompatible catanionic vesicles

The encapsulation of DNA by catanionic vesicles has been investigated; the vesicles are composed of one cationic surfactant, in excess, and one anionic. Since cationic systems are often toxic, we introduced a novel divalent cationic amino-acid-based amphiphile, which may enhance transfection and appears to be nontoxic, in our catanionic vesicle mixtures. The cationic amphiphile is arginine-N-lauroyl amide dihydrochloride (ALA), while the anionic one is sodium cetylsulfate (SCS). Vesicles formed spontaneously in aqueous mixtures of the two surfactants and were characterized with respect to internal structure and size by cryogenic transmission electron microscopy (cryo-TEM); the vesicles are markedly polydisperse. The results are compared with a study of an analogous system based on a short-chained anionic surfactant, sodium octylsulfate (SOS). Addition of DNA to catanionic vesicles resulted in associative phase separation at very low DNA concentrations; there is a separation into a precipitate and a supernatant solution; the latter is first bluish but becomes clearer as more DNA is added. From studies using cryo-TEM and small angle X-ray scattering (SAXS) it is demonstrated that there is a lamellar structure with DNA arranged between the amphiphile bilayers. Comparing the SOS containing DNA-vesicle complexes with the SCS ones, an increase in the repeat distance is perceived for SCS. Regarding the phase-separating DNA-amphiphile particles, cryo-TEM demonstrates a large and nonmonotonic variation of particle size as the DNA-amphiphile ratio is varied, with the largest particles obtained in the vicinity of overall charge neutrality. No major differences in phase behavior were noticed for the systems here presented as compared with those based on classical cationic surfactants. However, the prospect of using these systems in real biological applications offers a great advantage.     

Catanionic aggregates formed from drugs and lauric or capric acids enable prolonged release from gels

The aim of this study was to add to the range of charged surfactants that can be used to form catanionic aggregates with oppositely charged surface active drug substances; and to apply these aggregates to prolong drug release from gels. The surfactants used in this study, lauric and capric acids are of natural origin-unlike traditionally used, synthetic, surfactants. The mixtures of drug substances and oppositely charged surfactants were studied visually and with cryogenic transmission electron microscopy. Drug release from gels was studied with a modified USP paddle method. This study shows that lauric and capric acids are as, or even more, active in forming catanionic aggregates than traditionally used surfactants such as sodium dodecyl sulfate. It is shown that the length of the hydrophobic part of the surfactant plays an important role in the formation of pharmaceutically interesting catanionic aggregates. As seen in previous studies, using catanionic vesicles prolongs the drug release from gels and decreases the apparent diffusion coefficient by a factor of 10-50, compared to a gel containing only drug substance.     

Sugar-derived tricatenar catanionic surfactant: self-assembly and aggregation behavior in the cationic-rich side of the system

The aggregation behavior of the cationic-rich side of a sugar-based tricatenar catanionic mixture was investigated in water, and it was shown that the excess of cationic sugar-based surfactant enhanced vesicle stability as well as encapsulation properties. Moreover, when the system was diluted, the vesicular solution collapsed into a lamellar phase, whereas, when it was concentrated, no major impact on the shape and stability of the aggregates was observed. We also showed that both an increase in temperature and the addition of salt induced reversible vesicle aggregation, which appeared to be salt-specific, following the direct order of the Hofmeister series. A proper adjustment of these parameters should then enable better control of the shape, stability, and even encapsulation ability of the aggregates formed by these tricatenar cationic/anionic mixtures.