Study on size growth in the vesicle formation upon detergent removal from phospholipid/ detergent mixed micelles

When 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) was removed from the mixed CHAPS/EggPC micelles, large vesicles were prepared by dialysis or by slow step-by-step dilution, but small vesicles were prepared by fast one-step dilution. When sodium cholate was removed from the sodium cholate/EggPC micelles, small vesicles formed either by dialysis or by dilution; however, in the presence of 5 mM Ca²⁺ large vesicles were produced by dialysis, while small vesicles were prepared by dilution. The size growth was related to a detergent-induced fusion of the vesicles containing a large amount of detergent. Using spectrophotometry, quasielastic light scattering and freeze–fracture electron microscopy the fusion events were investigated both through the process of vesicle solubilization by adding detergent and through the process of vesicle formation by diluting a mixed micelle. The results suggest that a rapid CHAPS-induced fusion of the vesicles led to the large resultant vesicles and that no fusion of vesicles containing sodium cholate is responsible for the formation of small vesicles. Furthermore, the ultimate vesicle size related to rapid or slow detergent removal is dependent on the kinetic aspects of the fusion. Received: 19 August 1999 Accepted: 18 February 2000     

Phase Behavior of Bis(Quaternary Ammonium Bromide)/Sodium Cholate/H2O System

Interactions in an oppositely charged surfactant mixture composed of a gemini surfactant (bis(quaternary ammonium bromide)) and a bile salt (sodium cholate) in water were studied at 30°C. A combination of techniques was used including surface tension, conductometry, light scattering, light microscopy, and microelectrophoretic measurements. A strong dependence of the phase behavior on the molar ratio and actual concentration of surfactants was found. The interplay between electrostatic effects, geometry of molecules, and dissimilar separation of the hydrophobic and hydrophilic moieties in the surfactants dictate the interaction mode and the microstructures formed. Instead of precipitation, in the equivalent mixtures formation of complexes, mixed micelles, vesicles, coacervates, and solid crystalline phases have been observed. The extent of interacting forces in mixed micelles formed in equivalent mixtures was evaluated by regular solution theory. A relatively high negative value of interaction parameter indicated a strong attractive interaction between surfactants. The compositions of both mixed micelles and mixed monolayer are found to be almost equimolar.     

Adsorption, association and precipitation in hexadecyltrimethylammonium bromide/sodium dodecyl sulfate mixtures

The phase equilibria of surfactant aqueous mixtures, hexadecyltrimethylammonium bromide and sodium dodecyl sulfate, have been studied by polarizing microscopy, quasielastic light scattering, conductivity, potentiometric, electrophoretic, and surface tension measurements. Adsorption at the air/solution interface, association and precipitation in bulk solution strongly depended on the molar ratio and the concentration of surfactants. Catanionic vesicles coexisted with crystalline catanionic salts in a broad concentration range. The relative proportions of crystallites and vesicles varied according to the concentration and the molar ratio of the surfactants. The solid crystalline phase was progressively converted to catanionic vesicles with increasing surfactant molar ratio. At the highest excess of one of the surfactants transition from catanionic vesicles to mixed micelles occurred. The formation and stability of different phases are discussed in terms of surfactant molecular packing constraints and electrostatic interactions in the headgroup region. Surfactant tail-length asymmetry and the change of electrostatic interactions in the headgroup region from attractive to repulsive are governing factors for the transition from planar to curved bilayers. Received: 9 June 1998 Accepted: 18 August 1998     

Micelle-vesicle transition of oleyldimethylamine oxide in water

We studied the effects of the degree of ionization() and the surfactant concentration (C_d) on the micelle–vesicle transition in salt-free oleyldimethylamine oxide (OlDMAO) aqueous solutions by the dynamic light scattering (DLS), the hydrogen ion titration, the small angle neutron scattering (SANS), the electrophoretic light scattering (ELS) and viscoelastic measurements. From the study of ionization effects, the micelle–vesicle transition was recognized as a change of aggregate size by the DLS measurement; however, the micelle–vesicle transition was not detected both in the ELS measurement and the hydrogen ion titration, suggesting that the electric properties of the worm-like micelles and the vesicles are very similar despite a large difference of shapes between them. From the results of the SANS, the DLS and the viscosity measurements, it was suggested that a concentration-dependent micelle–vesicle transition took place around C_p = 10 mmol kg⁻¹ for the solutions at = 0.5. In the concentration-range 10 mmol kg⁻¹ < C_d < 150 mmol kg⁻¹, the micelles and the vesicles coexisted. In the concentration region (C_d = 10–50 mmol kg⁻¹), the vesicle size increased with the surfactant concentration.     

Polyelectrolyte-surfactant complexes formed by poly[3,5-bis(trimethylammoniummethyl)4-hydroxystyrene iodide]-block-poly(ethylene oxide) and sodium dodecyl sulfate in aqueous solutions

Formation of polyelectrolyte-surfactant (PE-S) complexes of poly[3,5-bis(trimethylammoniummethyl)-4-hydroxystyrene iodide]-block-poly(ethylene oxide) (QNPHOS-PEO) and sodium dodecyl sulfate (SDS) in aqueous solution was studied by dynamic and electrophoretic light scattering, small-angle X-ray scattering (SAXS), atomic force microscopy, and fluorometry, using pyrene as a fluorescent probe. SAXS data from the QNPHOS-PEO/SDS solutions were fitted assuming contributions from free copolymer, PE-S aggregates described by a mass fractal model, and densely packed surfactant micelles inside the aggregates. It was found that, unlike other systems of a double hydrophilic block polyelectrolyte and an oppositely charged surfactant, PE-S aggregates of the QNPHOS-PEO/SDS system do not form core-shell particles and the PE-S complex precipitates before reaching the charge equivalence between dodecyl sulfate anions and QNPHOS polycationic blocks, most likely because of conformational rigidity of the QNPHOS blocks, which prevents the system from the corresponding rearrangement.     

Solubilization of negatively charged DPPC/DPPG liposomes by bile salts

The interactions of the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC) in 0.1 M NaCl (pH 7.4) with membranes composed of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) and mixtures of DPPC and DPPG at molar ratios of 3:1 and 1:1 were studied by means of high-sensitivity isothermal titration calorimetry (ITC), dynamic light scattering (DLS), and differential scanning calorimetry (DSC). The partition coefficients and the transfer enthalpies for the incorporation of bile salt molecules into the phospholipid membranes were determined by ITC. The vesicle-to-micelle transition was investigated by ITC, DLS, and DSC. The phase boundaries for the saturation of the vesicles and their complete solubilization established by ITC were in general agreement with DLS data, but systematic differences could be seen due to the difference in detected physical quantities. Electrostatic repulsion effects between the negatively charged bile salt molecules and the negatively charged membrane surfaces are not limiting factors for the vesicle-to-micelle transition. The membrane packing constraints of the phospholipid molecules and the associated spontaneous curvature of the vesicles play the dominant role. DPPG vesicles are transformed by the bile salts into mixed micelles more easily or similarly compared to DPPC vesicles. The saturation of mixed DPPC/DPPG vesicles requires less bile salt, but to induce the solubilization of the liposomes, significantly higher amounts of bile salt are needed compared to the concentrations required for the solubilization of the pure phospholipid systems. The different solubilization behavior of DPPC/DPPG liposomes compared to the pure liposomes could be due to a specific "extraction" of DPPG into the mixed micelles in the coexistence region.     

Small angle neutron scattering study of sodium dodecyl sulfate micellar growth driven by addition of a hydrotropic salt

The structures of aggregates formed in aqueous solutions of an anionic surfactant, sodium dodecyl sulfate (SDS), with the addition of a cationic hydrotropic salt, p-toluidine hydrochloride (PTHC), have been investigated by small angle neutron scattering (SANS). The SANS spectra exhibit a pronounced peak at low salt concentration, indicating the presence of repulsive intermicellar interactions. Model-independent real space information about the structure is obtained from a generalized indirect Fourier transformation (GIFT) technique in combination with a suitable model for the interparticle structure factor. The interparticle interaction is captured using the rescaled mean spherical approximation (RMSA) closure relation and a Yukawa form of the interaction potential. Further quantification of the geometrical parameters of the micelles was achieved by a complete fit of the SANS data using a prolate ellipsoidal form factor and the RMSA structure factor. The present study shows that PTHC induces a decrease in the fractional charge of the micelles due to adsorption at the micellar surface and consequent growth of the SDS micelles from nearly globular to rodlike as the concentration of PTHC increases.     

Temperature dependence of the interaction of cholate and deoxycholate with fluid model membranes and their solubilization into mixed micelles

The interaction of bile salts with model membranes composed of soybean phosphatidylcholine (SPC) and synthetic 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) was investigated using high sensitivity isothermal titration calorimetry (ITC). The partitioning and incorporation of the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC) from an aqueous phase (pure water or 0.1 M NaCl) into fluid bilayer vesicles was studied as a function of temperature and ionic strength. The thermodynamic parameters of partitioning were determined with a model taking electrostatic interactions into account. In addition, the solubilization of SPC and POPC vesicles with NaC and NaDC as a function of temperature was also studied by ITC and the phase diagrams for the vesicle to micelle transition at two different temperatures were established. Unsaturated phospholipids require higher amounts of detergent to be transformed into micelles compared to saturated phospholipids. In addition, the width of the coexistence region of mixed micelles and mixed vesicles is larger for phosphatidylcholines with unsaturated chains. A comparison of NaDC with NaC shows the higher solubilization effectiveness of NaDC in agreement with its lower cmc. Furthermore, increasing the ionic strength decreases the amount of bile salt necessary for the formation of mixed micelles, which is also expected from the decrease of the cmc with ionic strength due to the shielding of the charges of the bile salts.     

Characteristics of complexes composed of sodium hyaluronate and bovine serum albumin

Complexes composed of sodium hyaluronate (NaHA) and bovine serum albumin (BSA) were studied to elucidate the exact composition of the complex, the phase separation, the electrophoretic mobility and the size using dynamic light scattering (DLS) and electrophoretic light scattering (ELS), etc. The phase diagram of the mixed solutions was determined. The complexes were soluble in neutral or weakly acidic pH regions and showed phase separation in the more acidic pH region. From the concentration of Na+ released from NaHA when it binds to BSA, the ratios of BSA to NaHA of the complexes were determined. In the region of soluble complexes, one BSA molecule was determined to bind with 15 carboxylic groups of NaHA and in the region of insoluble complexes to bind with 6 carboxylic groups. At the phase separation point, 117 BSA molecules bound with one NaHA molecule and 17% of the carboxylic groups of NaHA did not contribute to the binding of BSA. The sizes of the complexes decreased from several microm to several hundred nm as the binding ratio of BSA increases. Decreases in the viscosities of the mixed solutions were consistent with the decreases of the sizes. From these results, a model of complex formation is proposed.     

Interactions in Aqueous Mixtures of Alkylammonium Chlorides and Sodium Cholate

The interactions of alkylammonium chlorides (the number of carbon atom per chain was either 12, 14, or 16) with sodium cholate have been investigated by a combination of techniques including light and electron microscopy, surface tension, conductivity, light scattering, and microelectrophoretic measurements. The phase behavior has strongly depended on the molar ratio and actual concentration of oppositely charged surfactants. The change in the composition of the aggregates leads to a shape transformation from globular to elongated micelles to open and/or closed bilayers (vesicles) and precipitation. The length of micelles has been found to decrease dramatically with the concentration shift to the micellar regions of either surfactant. Upon a moderate excess of one surfactant, the mean hydrodynamic diameter of aggregates increases and wormlike micelles and/or open and closed bilayers are formed. Microscopic observations of alkylammonium cholates (novel catanionic surfactants precipitated in and/or close to equimolar region) have shown the presence of a variety of morphologies including twisted ribbons, tubules and bundles of tubules.     

Structure and size of spontaneously formed aggregates in Aerosol OT/PEG mixtures: effects of polymer size and composition

Dynamic light scattering and Cryo-TEM measurements have allowed us to obtain the size and structure of spontaneous aggregates formed by mixtures of Aerosol OT, AOT, and ethylene glycol polymers of different molecular mass. The results presented in this work show that small unilamellar vesicles predominate in pure Aerosol OT solutions and in dilute polymer solutions mixed with AOT. In the latter case, elongated micelles coexist with unilamellar vesicles. When polymer concentration increases above a certain concentration, the small vesicles disappear and the size of the elongated micelles decreases to a radius compatible with spherical micelles. For PEG concentrations above the overlapping ones, spherical micelles coexist with very large aggregates probably formed by large rod like micelles or by superstructures of elongated micelles embedded in a polymer network. This behavior is consistent with theoretical models based in molecular mean-field theory [M. Rovira-Bru, D.H. Thompson, I. Szleifer, Biophys. J. 83 (2002) 2419]. The properties of the different types of aggregates are obtained by fluorescence spectroscopy and electrophoretic mobility measurements.     

光散射法研究氧化胺胶束与聚苯乙烯磺酸钠的相互作用

采用光散射法研究了十二烷基二甲基氧化胺(DDAO)胶束与聚苯乙烯磺酸钠(NaPSS)的相互作用,浊度滴定和激光光散射结果表明,DDAO胶束与NaPSS的相互作用受介质离子强度影响,但与胶束浓度无关,浊度滴定曲线出现一个转折点(β_c),而平均流体力学半径R_h对胶束离解度β的关系曲线出现2个转折点,在第一个转折点(β₁)时,胶束与NaPSS开始缔合,在第二个转折点(β₂)时,胶束与NaPSS的缔合达到饱和,β₂相当于浊度滴定曲线的转折β_c,β₂,和β₁不随离子强度而变化,采用β₁和β_c分别计算胶束与NaPSS发生缔合时的临界表面电荷密度,两者差距约为15％,电泳光散射也证实了β₁的存在.     

Investigation of the chiral surfactant N-dodecoxycarbonylvaline in electrokinetic chromatography: improvements in elution range and pH stability via mixed micelles and vesicles, and the hydrophobicity determination of basic pharmaceutical drugs

The chiral surfactant dodecoxycarbonylvaline (DDCV) has proven to be an effective pseudostationary phase for the separation of many enantiomeric pharmaceutical compounds. In this study the elution range and the prediction of octanol-water partitioning for the DDCV micellar system was examined. Through incorporation of DDCV in mixed micelles and unilamellar vesicles, enhancement of the elution range was observed. The mixed micelles contained a second anionic surfactant, sodium dodecyl sulfate (SDS), while the vesicles were composed of DDCV and the cationic surfactant cetyltrimethylammonium bromide (CTAB). Enantioselectivity, as well as other chromatographic and electrophoretic parameters, were compared between the mixed micelles, vesicles, and DDCV micelles. The hydrophobicity of the DDCV system was also evaluated as a predictor of n-octanol-water partition coefficients for 15 beta amino alcohols. The correlation between the logarithm of the retention factor (log k) and log P(ow) for seven hydrophobic beta-blockers and eight beta-agonists were r2 = 0.964 and r2 = 0.814, respectively.     

二价金属离子对磷脂聚集体的影响

通过浊度分析和激光光散射光谱研究了二价金属离子（Ca2＋、Cu2＋和Mn2＋）对蛋黄卵磷脂(EYPC)聚集态的影响.结果表明，自由的二价金属离子对EYPC囊泡有破坏作用,并使EYPC囊泡发生相转变,形成胶束;而与牛磺胆酸钠(TC)结合的二价金属离子使EYPC囊泡半径减小,但不破坏EYPC囊泡.     

BULK AND INTERFACIAL BEHAVIORS OF MIXED SYSTEM OF HEXADECYLPYRIDINIUM CHLORIDE AND Na+ 2-HYDROXY BENZOATE−

The micellization behavior of hexadecylpyridinium chloride usually called cetylpyridinium chloride (CPC) in presence of sodium salicylate ( NaSal) has been investigated. The surface tension, conductance and microcalorimetric methods have been employed to determine the critical micellar concentration (CMC) of CPC and NaSal mixed in different molar proportions. The interfacial area occupied by CPC in presence of NaSal, the free energy of adsorption and the energetics of micellizatton have been evaluated. The enthalpy of interaction of NaSal with CPC micelle has also been estimated from microcalorimetric measurements. The shear viscosity of the CPC-NaSal combination at equimolar proportion at different surfactant concentration and temperature, and also the shear viscosity of CPC-NaSal combination at different molarity ratios with a fixed surfactant concentration have been determined. The static and dynamic light scattering measurements of the CPC-NaSal system at different composition and in presence of NaCl have been reported. Worm-like micelles of concentration dependent dimension and intermicellar repulsive interaction have been envisaged.     

Transitions of organized assemblies in mixed systems of cationic bolaamphiphile and anionic conventional surfactants

The transition from vesicles to tubelike structures has been studied in mixed systems of cationic bolaamphiphile BPHTAB [biphenyl-4,4'-bis(oxyhexamethylenetrimethylammonium bromide)] and its oppositely charged conventional surfactants with transmission electron microscopy (TEM) and dynamic light scattering (DLS). This transition can be attributed to the fact that tube-like structures are more stable aggregates than vesicles because of the special molecular packing in the aggregates of the mixed systems. The effects of temperature and salt addition on this transition have also been investigated, and the rate of the transition was found to be strongly dependent on temperature. Addition of the appropriate amount of NaBr will accelerate the transition from vesicles to tube-like structures, but the vesicles will transform into micelles at higher salt concentration. Moreover, the micelle-vesicle transition can be realized by addition of n-octanol in the mixed system of BPHTAB/sodium caprate (SC) at higher salt concentrations.     

Aggregation behavior in mixed system of double-chained anionic surfactant with single-chained nonionic surfactant in aqueous solution

The aggregation behavior of mixed systems of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) or sodium bis(4-phenylbutyl) sulfosuccinate (SBPBS) with nonionic surfactant pentaethylene glycol mono-n-dodecyl ether (C12E5) have been studied by means of steady-state fluorescence, electrical conductivity, dynamic light scattering, transmission electron microscopy, electrophoretic light scattering and pyrene solubilization measurements. The critical concentrations for aggregation, micropolarity, mobility, solubilization capacity and morphology of aggregates are characterized. Two critical concentrations for aggregation are observed in the mixed surfactants, which may correspond to the formation of different kinds of aggregates. Moreover, it is more favorable for AOT-C12E5 to form mixed vesicles compared to SBPBS-C12E5 at higher mole fraction of C12E5. In addition, it is revealed that SBPBS-C12E5 mixture has larger solubilization capacity for pyrene than AOT-C12E5 system.     

(羟基喜树碱@胆酸钠)-层状双金属氢氧化物纳米杂化物的组装及表征

采用“药物修饰-共组装”法制备了(羟基喜树碱@胆酸钠)-层状双金属氢氧化物纳米杂化物. 先用胆酸钠(SCL)包裹羟基喜树碱(HCPT)形成胶束, 再与微反应器制备的层状双氢氧化物(LDH)纳米片共组装形成纳米杂化物, 其载药量可达12.9%, 杂化物中HCPT以高生物活性的内酯形式存在. 采用聚乙二醇(PEG)和羧甲基纤维素(CMC)分别对所制备的(HCPT@SCL)-LDH纳米杂化物进行了表面修饰, 结果表明, 纳米杂化物的分散性得到明显改善; PEG的修饰效果优于CMC, 所获得的PEG-(HCPT@SCL)-LDH杂化物的平均粒径可小至约70 nm, 具有良好的分散性和药物缓释效果. 其药物释放过程可用准二级动力学方程描述, 颗粒内部扩散是药物释放过程的控制步骤.     

Conformation and Aggregation Behavior of Polyelectrolyte with Primary Amino Pendant Groups in Water or THF/Water Binary Solvent Mixture and Their Effect on the Morphology of AOT Vesicles in Aqueous Media

Cationic polyelectrolyte with primary amine pendant groups, poly (4-vinyl benzyl amine hydrochloride salt) (poly (4-VBAHS)), was characterized by static light scattering. Using light scattering measurement, the conformation transition of poly (4-VBAHS) chains in pure water, and THF/H₂O (v/v: 1/3) binary solvent mixture was discussed. Concentration-dependent multiple morphologies including interpenetrating networks, tubular micelles, branched micelles, hexagonal phases, vesicles, and needle crystals were observed by TEM. In addition, effect of poly (4-VBAHS) on the morphology, stability, and critical vesicle/micelle concentration of anionic surfactant sodium bis (2-ethylhexyl) sulfosucciante vesicles were detected using dynamic light scattering, zeta potential, surface tension, and transmission measurements.     

Temperature effect on formation of sodium cholate micelles

The micellization of sodium cholate (NaC) at 293.2, 298.2, 303.2, 308.2, and 313.2 K by cholate anion concentration was studied over the pH range from 6.0 to 7.2. Using a stepwise association model of cholate anions without bound sodium counterions, the aggregation number (nmacr;) of the cholate micelles was evaluated and found to increase with the total concentration, indicating that the stepwise association model is applicable. The nmacr; values go up and down with increasing temperature; 17 at 298.2 and 12 at 313.2 K and at 60 mM of the sodium cholate. The fluorescence of pyrene was measured in sodium cholate solution to determine the critical micelle concentration (CMC), indicating a narrow concentration range for CMC. A sodium-ion-specific electrode was used to determine a relatively low degree of counterion binding to micelles, supporting the validity of the present association model of cholate anions. The aggregation numbers evaluated at a constant ionic strength of 0.15 and at lower but variable ionic strengths were similar except for higher cholate concentrations.