Nanovesicles Based on Mixtures of a Biantennary Glycolipid with Ionic Co‐Surfactants

A biantennary surfactant based on a synthetic C₁₆‐maltoside was chosen to prepare vesicles for a potential vesicular drug delivery system. The synthesis comprised of three stages: Initial synthesis of β‐d ‐maltose octaacetate was followed by glycosidation of 2‐hexyl‐decanol and final glycolipid deacetylation. Both α‐ and β‐anomers were prepared and their anomeric purity was evaluated by ¹H NMR. Owing to the low water solubility of the glycolipid, addition of ionic co‐surfactants was believed to promote the surfactant distribution, thus leading to smaller and more uniform vesicles. The assembly behavior of the surfactant systems was studied by contact penetration under an optical polarizing microscope, while interfacial properties were determined by surface tension measurements. Vesicles were prepared by injection of an ethanolic solution into bulk water and investigated by dynamic light scattering and field emission scanning electron microscopy. Contact of the surfactant mixtures with water indicated a high tendency to exhibit the lamellar phase and confirmed the expected low molecular solubility. These findings suggest a potential of the surfactant to form stable vesicles. Injection of an ethanolic surfactant solution into bulk water gave sub‐micrometer sized vesicles with a narrow size distribution. Application of ionic co‐surfactants reduced the vesicle size. In particular ～20 % of anionic SDS proved highly effective, lowering the vesicle size by nearly one decade, thus accessing nano‐sized vesicles. Encapsulation of a water‐soluble drug was achieved in a 76 ± 10 % efficiency.     

辅酶Ⅰ诱导阳离子囊泡的聚集和酶分散的研究

分别在500nm和340nm考察了由表面活性剂溴化N,N-二-十六烷基-Nα-6-三甲胺基己酰基-L-丙氨酰胺形成的阳离子囊泡,在氧化型辅酶Ⅰ(NAD+)或还原型辅酶Ⅰ(NADH)作用下,以及在乳酸脱氢酶和底物丙酮酸的存在下,吸光值随时间的变化。结果表明,由0.50mmol/L的表面活性剂形成的阳离子囊泡悬浮液中,NAD+浓度从0增加到2.40mmol/L,囊泡悬液外观没有明显变化,囊泡不形成聚集;而NADH浓度从0.25mmol/L增加到0.80mmol/L,囊泡悬浮液的吸光值明显增加,囊泡产生了聚集;在乳酸脱氢酶存在下,囊泡的聚集体随着NADH在酶反应过程中不断转化为NAD+,重新分散,借助电子显微镜观察到了囊泡的聚集和用酶进行分散后的状态。最后,用超滤方法考察了囊泡结合的NADH与初始NADH浓度的关系,囊泡结合的NADH最大量为0.33mmol/L。     

偶联阳离子表面活性剂和常用阴离子表面活性剂混合溶液的相分离和微观结构

The properties of aqueous two-phase system (ATPS) of mixed solution containing gemini cationic surfactant trimethylene-l,3-bis(dodecyldimethyl ammonium) bromide (12-3-12, 2Br-) and traditional anionic surfactant sodium dodecyl sulfate (SDS) with or without added salt have been studied. An ATPS is formed in a narrow region of the ternary phase diagram different from that of traditional aqueous cationic-anionic surfactant systems. In ATPS region, the lowest total concentration of surfactants varies with the mixing ratio of geminis to SDS. Photographs obtained from freeze-etching, negative-staining and transmission electron microscopy show that the microstructures of two phases are different from each other. Micelles and vesicles can coexist in a single phase. The addition of salts can change the phase diagram of ATPS. Furthermore, the added salts promote the aggregation of rod-like micelles to form coarse network structure that increase the viscosity of solutions. The negative ions of the added salts are the determining factor.     

Effect of the addition of the surfactant Tetronic 1307 on poly(ether sulfone) porous hollow-fiber membrane formation

Poly(ether sulfone) (PES) hollow-fiber membrane was prepared via a nonsolvent-induced phase-separation method, and the effect of the addition of the surfactant Tetronic 1307 on the membrane performance and characteristics was investigated. The phase diagram of the PES/N-methyl-2-pyrrolidone (NMP)/water system was clarified. When the polymer solution involved Tetronic 1307, the amount of water required to induce the phase separation decreased, which indicated that Tetronic 1307 was one kind of nonsolvent. The kinetics of phase separation for the PES/NMP/Tetronic 1307 system were studied by light-scattering measurements. With the addition of Tetronic 1307, delayed phase separation was observed, and the structure growth rate decreased. Scanning electron microscopy images for all of the membranes showed the formation of fingerlike macrovoids through the cross section. Membrane surface morphologies were measured by atomic force microscopy. The obtained results indicated that membrane with 7 wt % Tetronic 1307 had higher roughness parameters than original membrane without the addition of surfactant. Ultrafiltration experiment results showed that the addition of Tetronic 1307 brought about an increase in water permeability and decreased the rejection of dextran with a molecular weight of about 10,000. The contact angles of water on the membrane outer surface decreased with the addition of Tetronic 1307. This mean the membrane surface became more hydrophilic. Thus, the addition of Tetronic 1307 was useful for improving the water permeability and for obtaining a hydrophilic membrane surface. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

Vesicles from sucrose fatty acid esters

It has been confirmed, from observations with an electron microscope after staining negatively with aqueous uranyl acetate solutions and using a flourescent microscope, that sucrose fatty acid esters form closed vesicles. The range of particle size of the vesicle, consisting of chromatographically fractionated sucrose dilaurate, was apparently 70–700 nm in the longer diameter of individual vesicles based on the transmission electron microscopic (TEM) observation. The weight-average particle size was 424 nm as shown by means of the photon-correlation method. The amounts of 6-carboxyfluorescein trapped in the vesicles of sucrose fatty acid esters were determined, and it was ascertained that the volumes of the central water phase depended upon the acyl chain lengths of fatty acid residues. Further, the effect of the additives [cholesterol and dicetyl phosphate (DCP) was examined. As an example, the vesicle of sucrose stearate had a central water phase of 1.7 one water/mol ester, and showed a slow release of 6-carboxyfluorescein from the central water phase after preparation of the vesicle.     

Mixed Cationic Surfactant Vesicles in (Dioctadecyldimethylammonium Bromide)/NaCl and (Dioctadecyldimethylammonium Chloride)/NaBr Aqueous Dispersions

One of the most challenging characteristics not fully understood yet of the cationic surfactant salt dioctadecyldimethylammonium (DODA⁺) halide is concerned with the effects of the counterion (usually Br⁻ and Cl⁻) on the surfactant assembly into vesicle structures in aqueous solution. These counterions play a key role in the self-organization of DODA⁺ into bilayer structures. Differential scanning calorimetry (DSC) and dynamic light scattering (DLS) techniques were used here to investigate systematically the effects of the single salts NaCl and NaBr, respectively, on the thermal behavior and structural organization of the cationic dioctadecyldimethylammonium bromide and chloride (DODAB and DODAC) in water. The results undoubtedly indicate that the added Br⁻ or Cl⁻, respectively, into DODAC and DODAB aqueous dispersions, replaces partially the bound counterions (Cl⁻ and Br⁻) from the vesicles, yielding formation of DODAB/DODAC mixed vesicles. As a conclusion, single salts may be used to tune the thermal and structural characteristics of cationic vesicles.     

Spontaneous vesicle formation from trisiloxane-tailed gemini surfactant

The spontaneous vesicle formation from a novel trisiloxane-tailed gemini surfactant were reported. The surface tension measurements revealed that aggregates are formed, and dynamic light scattering (DLS) measurements suggested the aggregates are vesicles. The size and morphology were observed by transmission electron microscopy (TEM). The vesicle formation was further confirmed by dye entrapment studies.     

气溶胶微滴的蒸发及界面现象

用电动平衡仪和光散射技术研究气溶胶微滴蒸发及其伴随的界面现象.研究的系统有缓慢蒸发的有机物微滴、快速蒸发的水滴和含表面活性剂的水滴.实验结果表明:蒸发速率影响着微滴的温度;表面活性剂显著地降低了水滴的蒸发速率;表面电荷密度的增加会导致微滴的分裂.这些研究结论对控制工业装置中液滴的蒸发和燃烧过程有着重要意义.     

Preparation and Physicochemical Properties of Lauroyl-Glutamyl-Lysil-Lauroyl-Glutamate Vesicles

We investigate the compositions of vesicle formulation by assembling phase diagrams of the ternary components of lauroyl‐glutamyl‐lysil‐lauroyl‐glutamate (C₁₂‐GLG‐C₁₂) peptide‐based gemini‐type amphiphile/citric acid/water using visual and microscopic observations. To clarify interactions between C₁₂‐GLG‐C₁₂ and citric acid, turbidity and zeta potential of the mixtures were investigated. To improve the stability of metastable vesicles, appropriate additives were examined by measuring particle size and zeta potential, visual observation and transmission electron microscopy. The turbidity increased and the absolute value of zeta potential decreased with increasing citric acid concentration in C₁₂‐GLG‐C₁₂/citric acid solutions. Then, a metastable γ region having vesicles was formed. The stability of vesicles increased with increasing cholesterol concentrations. This result suggests that a coacervation has occurred due to the effective cross‐sectional area decreasing with increasing C₁₂‐GLG‐C₁₂ hydrophobicity, which was derived from inhibition of the carboxyl group dissociation. Furthermore, we hypothesized that the orientation of cholesterol between vesicle membranes is a contributing factor to improve the vesicle stability. From transmission electron microscopic observations, it was made clear that the vesicles consisting of cholesterol and C₁₂‐GLG‐C₁₂ at a molar ratio of 2:1 showed multilayered structures. The vesicles consisting of C₁₂‐GLG‐C₁₂, cholesterol and citric acid are expected to be used as transdermal drug delivery system carriers, as they can be easily prepared using biocompatible compounds without the use of organic solvents such as chloroform.     

Phase behavior of laundry surfactants in polar solvents

Laundry surfactants are usually mixtures of ionic and nonionic detergents that exhibit a complex phase behavior. Here the ternary phase behavior of an isotropic and a liquid crystalline (LC) surfactant mixture has been examined in water/solvent systems. The size of the LC area in the ternary phase diagram was correlated to solvent parameters including the dielectric constant and the Gordon cohesiveness parameter. The Gordon parameter was found to have a linear relationship with the amount of solvent needed to go from an LC to an isotropic state over a wide range of solvents from polar to apolar. For solvents in which no surfactant aggregation (micellar or inverted micellar) is expected, the size of the LC area is linear with the reciprocal of the dielectric constant of the solvent. On diluting practical detergent liquids with water, a large LC area can be avoided by using solvents with a relatively low dielectric constant and with a relatively low molecular weight. The aggregated state of the surfactant mixtures in the isotropic regions of the phase diagram was studied using the solvatochromic fluorescent probe Nile Red. In the water corner of the phase diagram, the surfactants are aggregated into micelles. In strongly polar solvents, such as glycerol, ethylene glycol, formamide, and ethanolamine, the surfactants are also aggregated into micelles. In somewhat less polar solvents, such as methanol, ethanol, and t-butanol, the surfactant molecules are randomly distributed. In the surfactant-rich corner of the phase diagram of the isotropic mixture, the surfactant forms inverted micelles. An inverted micelle-to-micelle transition could be observed on dilution in ethylene glycol as a discontinuity in the trend of the Nile Red fluorescence maxima.     

Phase behavior of a fragrance compound system: Water/phenethyl alcohol/laureth 4/glycerol

The phase diagram of the system water/phenethyl alcohol (PEA)/Laureth 4 (L4)/glycerol was determined using visual observation, optical microscopy, small-angle X-ray diffractometry, and the vapor pressure of phenethyl alcohol measured by gas chromatographic analysis of headspace vapor at equilibrium. The phase diagram was shown to be dominated by three narrow isotropic liquid solubility regions along the water/glycerol, glycerol/PEA, and PEA/L4 axes. Vapor pressure measurements and tie-line determinations showed the final state of formulations after evaporation of water to be emulsions of glycerol/PEA-in-L4/PEA or L4/PEA-in-glycerol/PEA. PEA was predominantly dissolved in the L4/PEA phase because the chemical potential of PEA in glycerol was high, even at modest concentrations.     

Synergism in mixed monolayers of alkylpolyglucoside and alkylsorbitan surfactants at liquid/liquid interface

A study of nonideal behavior in the formation of mixed monolayers at the oil-water interface was performed for a nonionic-nonionic surfactant system. Mixtures containing alkylpolyglucoside and alkylsorbitan derivatives were investigated. As the oily phase, colza-rapeseed and olive oils were used. To evidence a synergetic effect in the interfacial tension reduction in the oil-water-surfactant-cosurfactant system, the model based on the regular solution theory was modified for the case of both surfactants being soluble in the water as well as in the oily phase. For determination of the condition for the synergism and the point of the maximum synergetic effect, the molar fraction in the mixed monolayer X ^s and the interaction parameter β^s were calculated, using experimental data for the interfacial tension and for the partition coefficient. A set of general equations was developed, to allow the analysis of a mixture containing a water-soluble and an oil-soluble surfactant. The equations are applied according the characteristics of studied quaternary systems. The mathematical model was tested with literature data, and the results were compared with those obtained from the phase diagram of oil-water-mixed surfactant system. The systems water-vegetable oil-alkylpolyglucoside-alkylsorbitan show a maximum synergetic effect at molar fractions between 0.85 and 0.90. The liquid-liquid interfacial tension and partition coefficient data were used to calculate the point of the maximum synergetic effect, i.e., the surfactant-cosurfactant ratio, which ensures the interfacial tension miniumum. The dramatic reduction in interfacial tension due to the presence of the surfactant mixture at the interface at the point of the synergism maximum is related to the formation of three-phase and single-phase microemulsions. The results were applied to obtain single-phase microemulsion in water-vegetable oil-alkylpolyglucoside-alkylsorbitan systems.     

Assembly properties of the aggregates resulting in the solubilization of phosphatidylcholine bilayers by sodium cholate

The interaction of sodium cholate with phosphatidylcholine liposomes was investigated. Permeability alterations were detected as a change in 5(6)-carboxyfluorescein (CF) released from the interior of vesicles and bilayer solubilization as a decrease in the static light-scattered by liposomes. Free surfactant concentration at subsolubilizing and solubilizing levels showed, respectively, values that were lower than and similar to the surfactant critical micelle concentration, and indicated that permeability alterations and solubilization were determined, respectively, by the action of surfactant monomer and by the formation of mixed micelles. A direct relationship was established in the initial steps [effective surfactant/lipid molar ratio (Re) lower than 0.07] between the growth of vesicles, the leakage of entrapped CF (fluidity of vesicles), and Re. These changes could be correlated with the increasing presence of surfactant molecules in the outer monolayer of vesicles and its saturation. The subsequent increase in Re led to a lower growth of vesicles in coexistence with a similar increase in the CF release. This behavior could be related to a increased rate of flipflop of the sodium cholate molecules, making the inner monolayer also available for the interaction with added surfactant. A direct dependence was also established in the initial solubilization steps (Re values up to 0.6) between the surfactant-phosphatidylcholine aggregate size, the static light-scattering of the system, and Re. In the Re interval 0.36–0.84 mixed vesicles and mixed micelles coexisted.     

Efficient Encapsulation of a Water-Soluble Molecule into Lipid Vesicles Using W/O/W Multiple Emulsions via Solvent Evaporation

We developed a novel method for preparing lipid vesicles with high entrapment efficiency and controlled size using water‐in‐oil‐in‐water (W/O/W) multiple emulsions as vesicle templates. Preparation consists of three steps. First, a water‐in‐oil (W/O) emulsion containing to‐be‐entrapped hydrophilic molecules in the water phase and vesicle‐forming lipids in the oil phase was formulated by sonication. Second, this W/O emulsion was introduced into a microchannel emulsification device to prepare a W/O/W multiple emulsion. In this step, sodium caseinate was used as the external emulsifier. Finally, organic solvent in the oil phase was removed by simple evaporation under ambient conditions to afford lipid vesicles. The diameter of the prepared vesicles reflected the water droplet size of the primary W/O emulsions, indicating that vesicle size could be controlled by the primary W/O emulsification process. Furthermore, high entrapment yields for hydrophilic molecules (exceeding 80 % for calcein) were obtained. The resulting vesicles had a multilamellar vesicular structure, as confirmed by transmission electron microscopy.     

非水微乳体系相图研究

研究了以甲醇或甲酰胺为极性相,正辛烷为油相,添加不同HLB值的表面活性剂形成的非水微乳体系的三元相图.结果表明,具有适当HLB值的表面活性剂可与正辛烷、甲醇或甲酰胺形成单相区,亲水性强的表面活性剂不利于形成单相微乳体系;在m(表面活性剂):m(正辛烷)=1∶4,甲醇(甲酰胺)增溶量为最大增溶量的50％时,各微乳液相点的粒径在20～60 nm.     

含Gemini成分的正负离子表面活性剂混合体系的双水相

研究了羧酸盐Gemini表面活性剂(C11pPHCNa)与季铵盐普通表面活性剂(DTAB)混合体系的双水相(pH =12)。结果表明,在恒定总浓度cT时改变混合比R,或恒定R改变cT,双水相上下相外观均发生改变,负染色电镜观测证实这是由上下相囊泡尺寸的变化所致。双水相的分相时间曲线出现一最低点,这可能与囊泡本身的性质以及囊泡之间的相互作用有关。     

拟三元相图在农药水乳剂配方筛选中的应用研究

以阿维菌素为例,通过拟三元相图系统研究了非离子与阴离子表面活性剂及其不同复配比例、油相中有效成分不同含量及不同水质下阿维菌素溶液/表面活性剂/水体系的相行为。研究结果表明,非离子表面活性剂与阴离子表面活性剂混用时水乳区面积比单用时面积要小,且随着非离子表面活性剂与阴离子表面活性剂比例的增加,水乳区的面积先减小后增大。而随着油相中阿维菌素的含量及水硬度的增加,水乳区面积有所增加,但影响不大。     

无机盐对十六烷基三甲基溴化铵（CTAB）微乳液相行为的影响

微乳液通常由水、油、盐、表面活性剂及助剂组成,各组分对微乳液体系的相行为及增溶情况都有影响。本文利用Winsor相图和ε-β鱼状相图来研究无机盐种类、浓度对十六烷基三甲基溴化铵（CTAB）型微乳液相行为的影响。研究发现,随着无机盐浓度或醇量增加,微乳液都会发生从WinsorⅠ→WinsorⅢ→WinsorⅡ的相转变,但具有不同阳离子或阴离子的无机盐对微乳液体系相行为的影响不同。无机盐在微乳液体系中主要与表面活性剂的反离子发生作用,对阳离子表面活性剂配成的微乳液体系,无机盐阴离子的作用比较强,且价态越高,离子半径越大,对微乳液相态的影响越大。通过对不同无机盐条件下的界面组成及增溶参数分析可知：无机盐种类的改变对鱼头、鱼尾点表面活性剂含量及醇在界面层中的分布影响较小;无机盐中阴离子改变对微乳液增溶能力影响较大,阳离子的改变对微乳液增溶能力影响较小。     

微乳轧制油拟三元相图及电导率的研究

以多组分表面活性剂的复配体系为研究对象,系统研究了表面活性剂-正丁醇-矿物油-水体系一系列拟三元相图,并用电导率法确定了微乳液结构。结果表明,表面活性剂复配比例不同对拟三元相图影响很大,随着Span80-PEG400比例逐渐增加,微乳区的面积先增大后减小,液晶区的面积逐渐减小,直到消失,相转变途径由非连续(液晶)向双连续过渡。随着表面活性剂含量的降低,有大面积的乳液区出现,电导率的变化与相变化存在一致性。     

Synthesis,characterization, and properties of amphiphilic block copolymer of acrylamide‐styrene by self‐emulsifying microemulsion method

The copolymerization system of acrylamide (AM) and styrene (St) was acquired by using amphiphilic block copolymer PAM‐b‐PSt with lower molecular weight as polymeric surfactant, and then the microemulsion phase diagram was drawn. The appropriate copolymerization systems were chosen in the phase diagram, and higher molecular weight amphiphilic block copolymers PAM‐b‐PSt were prepared by self‐emulsifying microemulsion method. The chemical composition and structure of the products were analyzed by FTIR, ¹H‐NMR, ¹³C‐NMR, GPC, and UV; the block structure of products was characterized by DSC, and the hydrophobic association property of the products was studied by the fluorescence probe and rotating viscosity measurement. The results showed that O/W microemulsion was also acquired by using the polymeric surfactant; 3 g polymeric surfactant was only used to disperse 0.25 g St into aqueous solution, which showed higher emulsifying efficiency. At the same time, the use of self‐emulsifying microemulsion copolymerizing system can avoid back treatment of small molecular surfactant and the purified block polymer was prepared in one step; the prepared copolymers have good hydrophobic association properties and their aqueous solution showed evident viscosity increment. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009