Gelation of spontaneously formed catanionic vesicles by water soluble polymers

The gelation of two spontaneously formed charged catanionic vesicles by four water soluble polymers was systematically studied by tube inversion method and rheology. Eight phase maps were successfully documented for the catanionic vesicle–polymer mixtures. The experimental results, as represented by the relaxation time and the storage modulus at 1 Hz, revealed that the catanionic vesicle–polymer interactions at play were of electrostatic and hydrophobic origin. Firstly, no association between charged catanionic vesicles and the polymer without charge/hydrophobic modification was observed due to lack of both electrostatic and hydrophobic effects. Secondly, hydrophobic interactions accounted for the association between the hydrophobically modified polymer without charge and charged catanionic vesicles with hydrophobic grafts of the polymer inserting in the catanionic vesicle bilayer. Thirdly, the positively charged polymer without hydrophobic modification could interact with negatively charged catanionic vesicles through electrostatic force on one hand but could not interact with positively charged catanionic vesicles on the other hand. Finally, the positively charged polymer with hydrophobic modification could interact both electrostatically and hydrophobically with negatively charged catanionic vesicles, resulting in the formation of strong gels. The hydrophobic interaction might even overcome the unfavorable electrostatic interaction between the positively charged vesicles and the polymer with positive charge/hydrophobic modification.     

Highly efficient capture and long-term encapsulation of dye by catanionic surfactant vesicles

Vesicles formed from the cationic surfactant, cetyltrimethylammonium tosylate (CTAT) and the anionic surfactant, sodium dodecylbenzenesulfonate (SDBS), were used to sequester the anionic dye carboxyfluorescein. Carboxyfluorescein was efficiently sequestered in CTAT-rich vesicles via two mechanisms: encapsulation in the inner water pool and electrostatic adsorption to the charged bilayer. The apparent encapsulation efficiency (22%) includes both encapsulated and adsorbed fractions. Entrapment of carboxyfluorescein by SDBS-rich vesicles was not observed. Results show the permeability of the catanionic membrane is an order of magnitude lower than that of phosphatidylcholine vesicles and the loading capacity is more than 10 times greater.     

Silicone nanocapsules templated inside the membranes of catanionic vesicles

A simple and effective way to synthesize hollow silicone resin particles of controlled diameter is presented. The synthesis utilizes catanionic vesicles as templates for the polycondensation/polymerization processes of 1,3,5,7-tetramethylcyclotetrasiloxane (D4H) within their membranes. Two different surfactant systems were used to form the vesicular templates: mixtures of dodecyltrimethylammonium bromide (DTAB) and sodium dodecylbenzenesulfonate (SDBS) in the cationic (the DTAB/SDBS system) or anionic (the SDBS/DTAB system) rich region of the phase diagram. The templates obtained from these surfactant mixtures form spontaneously unilamellar vesicles in aqueous solution. The vesicular templates swell upon addition of D4H, thus increasing their size. The silicone resin was obtained in acid- or base-catalyzed polycondensation and ring-opening polymerization processes of D4H. In the case of the DTAB/SDBS system the formation of a densely cross-linked silicone material with SiO3/2 units allowed the nanocapsules to retain the vesicular shape after removal of the template, whereas in the SDBS/DTAB system, the polymer produces capsules which are too smooth to support surfactant lysis. The morphology of the silicone nanocapsules was analyzed using transmission electron microscopy (TEM) and, in some cases, atomic force microscopy (AFM). TEM and AFM reveal discrete hollow particles with a small amount of linked or aggregated hollow silica shells.     

Sugar-derived tricatenar catanionic surfactant: synthesis, self-assembly properties, and hydrophilic probe encapsulation by vesicles

A new sugar-derived tricatenar catanionic surfactant (TriCat) was developed to obtain stable vesicles that could be exploited for drug encapsulation. The presence of the sugar moiety led to the formation of highly hydrophilic stoichiometric catanionic surfactant systems. The three hydrophobic chains permitted vesicles to form spontaneously. The self-assembly properties (morphology, size, and stability) of TriCat were examined in water and in buffer solution. Encapsulation studies of a hydrophilic probe, arbutin, commonly used in cosmetics for its whitening properties, were performed to check the impermeability of the vesicle bilayer. The enhancement of hydrophobic forces by the three chains of TriCat prevented surfactant equilibrium between the bilayer and the solution and enabled the probe to be retained in the aqueous cavity of the vesicles for at least 30 h. Thus, the present study suggests that this tricatenar catanionic surfactant could be a promising delivery system for hydrophilic drugs.     

Phase behavior and properties of reverse vesicles in salt-free catanionic surfactant mixtures

Salt-free 1:1 cationic/anionic (catanionic) surfactant mixture tetradecyltrimethylammonium laurate (TTAL) could be prepared by mixing equimolar tetradecyltrimethylammonium hydroxide (TTAOH) and lauric acid (LA) in water. Given the condition of suitable range of weight fraction of TTAL in total surfactant, rho=WTTAL/(WTTAL+WLA), and at existence of a small amount of water, it was found that the mixtures of so-obtained TTAL and LA could spontaneously form stable reverse vesicles in various organic solvents including toluene, tert-butylbenzene, and cyclohexane. The reverse vesicle phase shows a blue color against room light and exhibits strong birefringence under polarized microscope. The reverse vesicles are very sensitive to temperature change. Increasing temperature could make the rho values within which reverse vesicles were constructed move to higher values. In organic solvents of alkanes such as n-heptane, reverse vesicles could still form but become unstable upon time and centrifugation. Increasing temperature could accelerate phase separation, and finally a gel-like bottom phase was usually observed. Interestingly, the stable reverse vesicles formed by so-called salt-free catanionic surfactant mixtures still show some resistance against adding inorganic salts. They can trap inorganic ions such as Zn2+ and S2- into their hydrophilic layers. This opens the door for template applications of reverse vesicles to prepare inorganic nanoparticles.     

Cosolvent effects on the stability of catanionic vesicles formed from ion-pair amphiphiles

Four ion-pair amphiphiles (IPAs), derived from the pairing of alkyltrimethylammonium chlorides and sodium alkyl sulfates, were used to form catanionic vesicles in water upon the mechanical dispersion method. For the first time in the literature, short-chained alcohols (methanol, ethanol, 1-propanol, and 1-butanol) were added as cosolvents at a variety of concentrations and systematically studied for their effects on the stability of the ensuing vesicles. Dynamic light scattering measurements indicated that vesicles formed from one of the IPAs (i.e., dodecyltrimethylammonium dodecyl sulfate) could be efficiently and successfully stabilized by the addition of appropriate amounts of 1-propanol and 1-butanol. Maximum lifetimes of more than 1 year and 132 days for stable vesicles in 5% 1-butanol and 15% 1-propanol solutions, respectively, were observed, and this demonstrates that a novel method for the stabilization of catanionic vesicles formed from IPAs becomes available by means of cosolvent addition. Furthermore, the stability of catanionic vesicles was found to be strongly dependent on cosolvent concentration. In general, the vesicle stability increased with increasing the cosolvent concentration, reached a maximum at a specific concentration, and thereafter decreased with further increasing the concentration. The vesicles finally disintegrated into constituent molecules in solutions of high cosolvent concentrations. An explanation of cosolvent effects based on the medium dielectric constant was proposed.     

Investigations into the bending constant and edge energy of bilayers of salt-free catanionic vesicles

Using molecular dynamics simulation, we performed theoretical calculations on the curvature constant and edge energy of bilayers of salt-free, zero-charged, cationic and anionic (catanionic) surfactant vesicles composed of alkylammonium cations (C(m)(+)) and fatty acid anions (C(n)(-)). Both the minimum size and edge energy of vesicles were calculated to examine the relation between the length of the surfactant molecules and the mechanical properties of the catanionic bilayers. Our simulation results clearly demonstrate that, when the chain lengths of the cationic and anionic surfactants are equal, both the edge energy and the rigidity of the catanionic bilayers increase dramatically, changing from around 0.36 to 2.77 kBT·nm(-1) and around 0.86 to 6.51 kBT·nm(-1), respectively. For the smallest catanionic vesicles, the curvature is not uniform and the surfactant molecules adopt a multicurvature arrangement in the vesicle bilayers. We suspect that the multicurvature bending of bilayers of catanionic vesicles is a common phenomenon in rigid bilayer systems, which could aid understanding of ion transport through bilayer membranes.     

Thermotropic behavior of asymmetric chain length catanionic surfactants: the influence of the polar head group

Catanionic surfactants formed by the pairing of two ionic amphiphilic chains of opposite charge are now recognized as an important class of amphiphiles. Many aspects of their phase behavior have yet to be explored. In this work, two homologous series of catanionic surfactants were synthesized, based on the cationic headgroups trimethylammonium and pyridinium. Within each series, the headgroup and chain length of the cationic counterpart remains constant while for the anionic counterpart the headgroup is varied, while its alkyl chain length is also kept constant. Thus, one can directly monitor the influence of headgroup chemistry on the thermal behavior of these compounds. Differential scanning calorimetry (DSC) and polarizing light microscopy show that these compounds bear a rich and often complex thermotropic behavior, with the headgroup chemistry in some instances having a rather dramatic influence on phase behavior. Several liquid crystalline phases appear between the solid crystalline phase and the isotropic liquid phase. A qualitative correlation between the observed thermotropic behavior and the chemical nature of headgroup is presented.     

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.     

Flow cytometric characterization of interactions between U-937 human macrophages and positively charged catanionic vesicles

Catanionic vesicles are considered a potential alternative to liposomes for drug delivery systems because of their greater stability and lower cost. Before using catanionic vesicles in vivo, their interactions with macrophages must be fully understood because they are primarily removed from circulation by the macrophages of the mononuclear phagocyte system. Using flow cytometry, we examined the intracellular responses-reactive oxygen species (ROS) content, mitochondrial membrane potential, cell size and complexity, and cell cycle profiles-in U-937 human macrophages treated with positively charged catanionic vesicles. Kinetic hydrogen peroxide production initially increased at lower concentrations (4-10nM) but declined at higher concentrations (40 nM and 80 nM) over the entire incubation period. Superoxide content generation, however, increased over the entire concentration range and incubation period. Catanionic vesicles decreased mitochondrial membrane potential for every concentration after 4h of incubation but caused a significant fluctuation in mitochondrial membrane potential at 6h. After 6h of incubation, catanionic vesicles produced more changes in cell size and complexity than after 4h. The increase in the subG1 population of cells treated with catanionic vesicles at higher doses indicated that apoptosis progressed. Positively charged catanionic vesicles induced different activated patterns of ROS generation and changes in mitochondrial membrane potential than did cationic liposomes. The nature of the interactions between macrophages and catanionic vesicles is of great importance for the design of safer and more effective delivery systems for macrophages. Our findings contribute to a better understanding of the molecular action of catanionic vesicles in the cellular system.     

Densely stacked multilamellar and oligovesicular vesicles, bilayer cylinders, and tubes joining with vesicles of a salt-free catanionic extractant and surfactant system

In the phase diagram of an excellent extractant of rare earth metal ions, di(2-ethylhexyl) phosphate (HDEHP, commercial name P204), mixing with a cationic trimethyltetradecylammonium hydroxide (TTAOH) in water, a birefringent Lalpha phase was found, which consists of densely stacked multilamellar vesicles. The densely stacked multilamellar vesicles are remarkably deformed, as observed by means of cryotransmission electron microscopy (cryo-TEM). Further, self-assembled structures-oligovesicular vesicles, bilayer cylinders, and tubes joining with vesicles-were also observed. The self-assembled phase is transparent, anisotropic, and highly viscous, possessing elastic properties determined by rheological measurements. This is the first time that birefringent Lalpha phase with remarkably deformed amphiphilic bilayer membranes has been constructed through combining a hydrophobic organic extractant having double chains with a water-soluble surfactant having a single chain, which may direct primarily toward acquiring an understanding of the mechanism of salt-free catanionic vesicles and secondarily to determine if vesicle-extraction technology utilizing extractants is possible.     

Gel formation in systems composed of drug containing catanionic vesicles and oppositely charged hydrophobically modified polymer

The aim of this study was to explore if mixtures of drug containing catanionic vesicles and polymers give rise to gel formation, and if so, if drug release from these gels could be prolonged. Catanionic vesicles formed from the drug substances alprenolol or tetracaine, and the oppositely charged surfactant sodium dodecyl sulphate were mixed with polymers. Three polymers with different properties were employed: one bearing hydrophobic modifications, one positively charged and one positively charged polymer bearing hydrophobic modifications. The structure of the vesicles before and after addition of polymer was investigated by using cryo-TEM. Gel formation was confirmed by using rheological measurements. Drug release was studied using a modified USP paddle method. Gels were observed to form only in the case when catanionic vesicles, most likely with a net negative charge, were mixed with positively charged polymer bearing lipophilic modifications. The release of drug substance from these systems, where the vesicles are not trapped within the gel but constitute a founding part of it, could be significantly prolonged. The drug release rate was found to depend on vesicle concentration to a higher extent than on polymer concentration.     

Spontaneous formation of vesicles and dispersed cubic and hexagonal particles in amino acid-based catanionic surfactant systems

Mixed catanionic surfactant systems based on amino acids were investigated with respect to the formation of liquid crystal dispersions and the stability of the dispersions. The surfactants used were arginine-N-lauroyl amide dihydrochloride (ALA) and N(alpha)-lauroyl-arginine-methyl ester hydrochloride (LAM), which are arginine-based cationic surfactants; sodium hydrogenated tallow glutamate (HS), a glutamic-based anionic surfactant; and the anionic surfactants sodium octyl sulfate (SOS) and sodium cetyl sulfate (SCS). It is demonstrated that in certain ranges of composition there is a spontaneous formation of vesicular, cubic, and hexagonal structures. The solutions were characterized with respect to internal structure and size by cryogenic transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and turbidity measurements. Vesicles formed spontaneously and were found for all systems studied; their size distribution is presented for the systems ALA/SCS/W and ALA/SOS/W; they are all markedly polydisperse. The aging process for the system ALA/SOS/W was monitored both by turbidity and by cryo-TEM imaging; the size distribution profile for the system becomes narrower and the number average radius decreases with time. The presence of dispersed particles with internal cubic structure (cubosomes) and internal hexagonal structure (hexosomes) was documented for the systems containing ALA and HS. The particles formed spontaneously and remained stably dispersed in solution; no stabilizer was required. (Cubosome and hexosome are USPTO registered trademarks of Camurus AB, Sweden.) The spontaneous formation of particles and their stability, together with favorable biological responses, suggests a number of applications.     

Spontaneous vesicle formation in catanionic mixtures of amino acid-based surfactants: chain length symmetry effects

The use of amino acids for the synthesis of novel surfactants with vesicle-forming properties potentially enhances the biocompatibility levels needed for a viable alternative to conventional lipid vesicles. In this work, the formation and characterization of catanionic vesicles by newly synthesized lysine- and serine-derived surfactants have been investigated by means of phase behavior mapping and PFG-NMR diffusometry and cryo-TEM methods. The lysine-derived surfactants are double-chained anionic molecules bearing a pseudogemini configuration, whereas the serine-derived amphiphile is cationic and single-chained. Vesicles form in the cationic-rich side for narrow mixing ratios of the two amphiphiles. Two pairs of systems were studied: one symmetric with equal chain lengths, 2C12/C12, and the other highly asymmetric with 2C8/C16 chains, where the serine-based surfactant has the longest chain. Different mechanisms of the vesicle-to-micelle transition were found, depending on symmetry: the 2C12/C12 system entails limited micellar growth and intermediate phase separation, whereas the 2C8/C16 system shows a continuous transition involving large wormlike micelles. The results are interpreted on the basis of currently available models for the micelle-vesicle transitions and the stabilization of catanionic vesicles (energy of curvature vs mixing entropy).     

The review on properties of solid catanionic surfactants: Main applications and perspectives of new catanionic surfactants and compounds with catanionic assisted synthesis

Mixtures of anionic and cationic surfactants display varied aggregate structures. Solid catanionic systems and metaloamphiphilic complexes, amphiphilic host–guest systems, as well as amphiphilic hydrogen bond pairs are a kind of hybrid amphiphiles, all of which self-organize into supramolecular membranes. Amphiphilicity of the supermolecules drives their hierarchical self-assembly. This review mainly discusses the current applications of well-ordered catanionic materials that show a variety of functionalities in material and life science. Widely studied rational molecular design can create self-assembled structures through various noncovalent interactions combined with numerous modification strategies. Possible applications are at early stage to access the entire potential, but may provide new and interesting interdisciplinary directions for further studies.     

Network formation of catanionic vesicles and oppositely charged polyelectrolytes. Effect of polymer charge density and hydrophobic modification

In nonequimolar solutions of a cationic and an anionic surfactant, vesicles bearing a net charge can be spontaneously formed and apparently exist as thermodynamically stable aggregates. These vesicles can associate strongly with polymers in solution by means of hydrophobic and/or electrostatic interactions. In the current work, we have investigated the rheological and microstructural properties of mixtures of cationic polyelectrolytes and net anionic sodium dodecyl sulfate/didodecyldimethylammonium bromide vesicles. The polyelectrolytes consist of two cationic cellulose derivatives with different charge densities; the lowest charge density polymer contains also hydrophobic grafts, with the number of charges equal to the number of grafts. For both systems, polymer-vesicle association leads to a major increase in viscosity and to gel-like behavior, but the viscosity effects are more pronounced for the less charged, hydrophobically modified polymer. Evaluation of the frequency dependence of the storage and loss moduli for the two systems shows further differences in behavior: while the more long-lived cross-links occur for the more highly charged hydrophilic polymer, the number of cross-links is higher for the hydrophobically modified polymer. Microstructure studies by cryogenic transmission electron microscopy indicate that the two polymers affect the vesicle stability in different ways. With the hydrophobically modified polymer, the aggregates remain largely in the form of globular vesicles and faceted vesicles (polygon-shaped vesicles with largely planar regions). For the hydrophilic polycation, on the other hand, the surfactant aggregate structure is more extensively modified: first, the vesicles change from a globular to a faceted shape; second, there is opening of the bilayers leading to holey vesicles and ultimately to considerable vesicle disruption leading to planar bilayer, disklike aggregates. The faceted shape is tentatively attributed to a crystallization of the surfactant film in the vesicles. It is inferred that a hydrophobically modified polyion with relatively low charge density can better stabilize vesicles due to formation of molecularly mixed aggregates, while a hydrophilic polyion with relatively high charge density associates so strongly to the surfactant films, due to strong electrostatic interactions, that the vesicles are more perturbed and even disrupted.     

Kemp elimination in membrane mimetic reaction media: probing catalytic properties of catanionic vesicles formed from double-tailed amphiphiles

The rate-determining deprotonation of 5-nitrobenzisoxazole (Kemp elimination) by hydroxide is efficiently catalyzed by vesicles formed from dimethyldioctadecylammonium chloride (C(18)()C(18)()(+)()). Gradual addition of sodium didecyl phosphate (C(10)()C(10)()(-)()) leads to the formation of catanionic vesicles, which were characterized by cryo-electron microscopy, and their main phase transition temperatures (DSC) and zeta-potentials. Increasing percentages of C(10)()C(10)()(-)() in the vesicular bilayers decrease the catalysis of the Kemp elimination. A detailed kinetic analysis, supported by consideration of substrate binding site polarities and counterion binding percentages, suggest that the catalytic effects of C(18)()C(18)()(+)()/C(10)()C(10)()(-)() catanionic vesicles are primarily determined by the binding of catalytically active hydroxide ions to the vesicular surface area. The formation of neutral microdomains between 10 and 30 mol % of C(10)()C(10)()(-)() in the bilayer, as revealed by DSC, is not apparent from the catalytic effects found for these vesicles. Interestingly, the catalytic effects observed for 50 mol % C(10)()C(10)()(-)() in the catanionic vesicles indicate an asymmetric distribution of C(18)()C(18)()(+)() and C(10)()C(10)()(-)() over the bilayer leaflets. The overall kinetic results illustrate the highly complex mix of factors which determines catalytic effects on reactions occurring in biological cell membranes.     

Surface and interfacial segregation of polyethersulfone deuterated chain ends determined by neutron reflectivity

The surface localization of polymer chain ends has been shown to be an effective method for surface composition control in amorphous polymer films. This work determines chain end distribution in thin polyethersulfone (PESU) films end‐capped with deuterated compounds of varying size and composition. Neutron reflectivity revealed the preferential localization of chain ends to the PESU‐air interface, independent of chain end identity. The length scale of the chain end concentration gradient was determined to differ from that predicted for flexible chain polymers. Atomic force microscopy and contact angle analysis demonstrated that chain end localization allows for improved control of nanoscale and macroscale surface properties of PESU films. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017 , 55, 293–301     

Enhancing physical stability of positively charged catanionic vesicles in the presence of calcium chloride via cholesterol-induced fluidic bilayer characteristic

An ion pair amphiphile (IPA), hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS), and a double-chained cationic surfactant, dimethyldimyristylammonium bromide (DTDAB), could form positively charged catanionic vesicles with a potential application in gene delivery. To improve the gene delivery efficiency, the addition of CaCl₂ into cationic liposomal systems has been proposed in the literature. In this study, detrimental effect of calcium chloride on the physical stability of the positively charged HTMA-DS/DTDAB catanionic vesicles was demonstrated by the size and zeta potential analyses of the vesicles. It was noted that the reduced electrostatic interaction between the catanionic vesicles could not fully explain the lowered physical stability of the vesicles in the presence of CaCl₂. Apparently, the molecular packing/interaction in the vesicular bilayers played an important role in the vesicle physical stability. To modify the molecular packing/interaction in the vesicular bilayers, cholesterol was adopted as an additive to form catanionic vesicles with HTMA-DS/DTDAB. It was found that the physical stability of the catanionic vesicles was significantly improved with the presence of cholesterol in the vesicular bilayers even in the presence of 50 mM CaCl₂. An infrared analysis suggested that with the incorporation of cholesterol into HTMA-DS/DTDAB vesicular bilayers, the alkyl chain motion was enhanced, and the molecular packing became less ordered. The cholesterol-induced fluidic bilayer characteristic allowed the vesicular bilayers to be adjusted to a stable status, resulting in improved physical stability of the catanionic vesicles even in the presence of CaCl₂ with a high concentration.     

Investigation on the aggregation behaviors of DDAB/NaDEHP catanionic vesicles in the absence and presence of a negatively charged polyelectrolyte

The aggregation behaviors of the cationic and anionic (catanionic) surfactant vesicles formed by didodecyldimethylammonium bromide (DDAB)/sodium bis(2-ethylhexyl) phosphate (NaDEHP) in the absence and presence of a negatively charged polyelectrolyte are investigated. The amount of the charge on the vesicle can be tuned by controlling the DDAB/NaDEHP surfactant molar ratio. The charged vesicular dispersions made of DDAB/NaDEHP are mixed with a negatively charged polyelectrolyte, poly(4-styrenesulfonic acid-co-maleic acid) sodium (PSSAMA), to form complexes. Depending on the polyelectrolyte/vesicle charge ratio, complex flocculation or precipitation occurs. Characterization of the catanionic vesicles and the complexes are performed by transmission electron microscope (TEM), Cryo-TEM, dynamic light scattering (DLS), conductivity, turbidity, zeta potential, isothermal titration calorimetry (ITC) and small-angle X-ray scattering (SAXS) measurements.