Structure and dynamics of highly PEG-ylated sterically stabilized micelles in aqueous media

Molecular assemblies of highly PEG-ylated phospholipids are important in many biomedical applications. We have studied sterically stabilized micelles (SSMs) of self-assembled DSPE–PEG2000 in pure water and isotonic HEPES-buffered saline solution. The observed SSM sizes of 2–15 nm largely depend on the solvent and the lipid concentration used. The critical micelle concentration of DSPE–PEG2000 is 10 times higher in water than in buffer, and the viscosity of the dispersion dramatically increases with the lipid concentration. To explain the experimentally observed results, we performed atomistic molecular dynamics simulations of solvated SSMs. Our modeling revealed that the observed assemblies have very different aggregation numbers (N(agg) ≈ 90 in saline solution and N(agg) < 8 in water) because of very different screening of their charged PO4(–) groups. We also demonstrate that the micelle cores can inflate and their coronas can fluctuate strongly, thus allowing storage and delivery of molecules with different chemistries.     

Soluble complexes of sodium poly(isoprene-b-methacrylate) micelles with cationic surfactants in aqueous media

Water-soluble complexes between sodium poly(isoprene-b-methacrylate) (NaIMA) amphiphilic block copolymer micelles and two cationic surfactants with different hydrophobic tail lengths, namely, dodecyltrimethylammonium bromide (DTMAB) and octyltrimethylammonium bromide (OTMAB), were prepared by mixing individual aqueous solutions of block copolymers and surfactants. The complexes were characterized in terms of size, overall charge, and micropolarity by dynamic light scattering, zeta-potential measurements, and fluorescence spectroscopy. Properties of the systems were investigated as a function of surfactant concentration and surfactant type and state in the initial solutions, as well as temperature. Experiments reveal surfactant complexation at the coronal sodium poly(methacrylate) (NaMA) chains, followed by an increase in mass and a decrease in size of the micelles. Complexation of individual surfactant micelles was observed when the DTMAB concentration in the starting solutions was higher than the surfactant cmc. The complexes show a temperature dependence of their dimension due to the hydrophobic effect.     

Block copolymer micelles in aqueous media

Polystyrene-block-poly(methacrylic acid) and poly(methacrylic acid)-block-polystyrene-block-poly(methacrylic acid) di- and triblock copolymers form micelles with polystyrene cores and poly(methacrylic acid) shells when dissolved in water/1, 4-dioxane mixtures, rich in dioxane. These micelles can be transferred into water rich mixtures, into water, and into aqueous buffers by stepwise dialysis. Quasielastic light scattering and sedimentation velocity experiments show that in dioxane rich mixtures exists a dynamic micellization equilibrium, while in dioxane poor solutions and in aqueous buffers the equilibrium is frozen. The process of mixed micelles formation was observed in dioxane rich solutions.     

Kinetic and spectroscopic investigations of aqueous micelles of cationic surfactants

The aqueous micellar solutions of monocationic surfactants N-hexadecyl-N,N,N-trimethylammonium bromide (CTABr), N-hexadecyl-N,N,N-trimethylammonium nitrate (CTANO₃), N,N,N-tributyl-N-hexadecylammonium bromide (CTBABr) and gemini surfactants 1,4-bis(N-hexadecyl-N,N-dimethylammonium)ethane dibromide (C-E-C2Br), 1,4-bis(N-hexadecyl-N,N-dimethylammonium)propane dibromide (C-P-C2Br), and 1,4-bis(N-hexadecyl-N,N-dimethylammonium)butane dibromide (C-B-C2Br) were studied with a solvatochromic probe, 2,6-diphenyl-4-(2,4,6-triphenylpyridinium-1-yl)phenolate, better known as Reichard’s ET-30 dye. The local polarity at the probe site (E_T) was calculated from the wavelength maximum of the lowest-energy intramolecular charge-transfer ϖ-ϖ* absorption band of ET-30. The results were compared with a kinetic investigation of the cyclization of 2-(3-bromopropyloxy)phenoxide (PhBr7) in micelles; this reaction is a model for S_N2 reactions and it depends on medium polarity.     

Biological surfactants stabilizing natural microbubbles in aqueous media

Recent experimental work, using carbohydrate (agarose) gels derived from marine algae, has provided much evidence that largely hydrophobic surfactants surround and stabilize the long-lived gas microbubbles present in such aqueous gels. Later work involving three different types of protein-specific chemical tests further revealed that these biological surfactants, which were also found to be present (in much higher concentrations) in forest soils, are proteinaceous compounds whose surface activity depend upon aromatic amino acid residues. These proteinaceous surfactants have now been successfully isolated from both agarose and aqueous soil extracts and found to-have extremely similar total amino acid compositions. Electrophoresis showed that the microbubble surfactants from both natural sources migrated as a single (but somewhat diffuse) band with or without sulfhydryl-reducing reagent present, and the same apparent molecular weight (< 6,000 daltons), were stained by both peptide- and carbohydrate- specific reagents and, in effect, were essentially indistinguishable. Further electrophoresis experiments, involving enzymatic degradation of the isolated microbubble glycopeptide surfactant, verified the present of covalently bound carbohydrate in the microbubble surfactant. Thereafter, the glycopeptide surfactant was dansylated and chromatographed on Sephadex G-25 and LH-20 columns and, thereby, separated into five major fractions; it was calculated that the $\text{average}$ molecular weight of the microbubble glycopeptide surfactant (as a whole) was very close to 4,000 daltons. Moreover, the same dansyl NH₂-terminal amino acid, specifically alanine, was identified for all five major fractions. It is concluded that microbubble glycopeptide surfactant actually represents a small distribution of structurally similar surface-active glycopeptides, rather than a single molecular species. In addition, a selected review of the biochemical and natural-product organochemical literature further suggests that the microbubble surfactant is essentially a partial degradation product of larger, precursor glycoproteins, which are probably of biological exudate origin and are widely distributed in the environment.     

Local mobility of micelles of new cationic surfactants and their interactions with hydrophobically modified polyacrylamides

The local dynamics and organization of micelles of new long-chain cationic surfactants with saturated hydrocarbon fragments (from C₁₆ to C₂₂) are investigated via the EPR spin-probe technique. The local mobility of spin probes in the hydrocarbon core of a micelle changes insignificantly, while the order parameter noticeably increases with lengthening of the hydrocarbon fragment of the surfactant molecule. The specific features of the interaction of the surfactants with network junctions of the gels formed by two types of hydrophobically modified polyacrylamides??either containing charged groups (sodium acrylate) in the backbone or lacking these groups??are studied. In both cases, the local mobility of network junctions of the gel increases after the introduction of the surfactant (C₁₈). Moreover, for surfactant with a long alkyl group (C₂), the microscopic viscosity of the gel based on the uncharged polymer decreases, although the local mobility of the network junctions increases. Possible causes of the observed specific features are discussed.     

Interaction of cationic surfactants with carboxymethylcellulose in aqueous media

We have examined the polymer-surfactant interaction in mixed solutions of the cationic surfactants, i.e., dodecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, hexadecyltrimethylammonium bromide, tetradecyltriphenylphosphonium bromide, and tetradecylpyridinium bromide and a semiflexible anionic polyelectrolyte carboxymethylcellulose in water and aqueous salt solutions by various techniques: tensiometry, viscosimetry or ion-selective electrode method, and dynamic light scattering. We have investigated the effect of varying surfactant chain length, head group size, counterion, and ionic strength on the critical aggregation concentration (CAC) of mixed polymer surfactant systems and the collapse of the polymer molecule under different solution conditions. The CAC decreases with increasing alkyl chain length. Above a certain surfactant concentration, mixed aggregates start growing until their macroscopic phase separation. The growth is more rapid with greater surfactant tail length and with increasing head group size. This is attributed in both cases to the increasing hydrophobic interaction between polymer and surfactant. Among surfactants with monovalent halide counterions, iodide induces the strongest binding, reflected by the onset of growth of the mixed aggregates at low surfactant concentration. This is perhaps related to the decreasing hydration of the counterion from chloride to iodide. The surfactant concentration at which the viscosity of the solution starts to decrease sharply is smaller than the CAC, and probably reflects polymer chain shrinkage due to noncooperative binding.     

Wormlike micelles formed by mixed cationic and anionic gemini surfactants in aqueous solution

The formation and the properties of wormlike micelles in aqueous solutions of mixed cationic and anionic gemini surfactants, 2-hydroxyl-propanediyl-α,ω-bis(dimethyldodecylammonium bromide) (12-3(OH)-12) and O,O'-bis(sodium 2-dodecylcarboxylate)-p-benzenediol (C(12)?C(12)), have been studied by steady-state and dynamic rheological measurements at 25°C. With the addition of a small amount of C(12)?C(12) into the solution of 12-3(OH)-12, the total surfactant concentration of which was always kept at 80 mmol L(-1), the solution viscosity was strongly enhanced and its maximum was much larger than that of the mixed system of propanediyl-α,ω-bis(dimethyldodecylammonium bromide) (12-3-12) and C(12)?C(12). The results of dynamic rheology measurements showed that 12-3(OH)-12/C(12)?C(12) formed longer wormlike micelles in comparison with 12-3-12/C(12)?C(12). This was attributed to the effect of hydrogen bonding occurring between 12-3(OH)-12 molecules, which was an effective driving force promoting micellar growth. As few C(12)?C(12) participated in the micelles, the electrostatic attraction between the oppositely charged head groups of 12-3(OH)-12 and C(12)?C(12) made the molecules in the aggregates pack more tightly. This reinforced the hydrogen-bonding interactions and greatly promoted the micellar growth.     

Modulation of dynamics and reactivity of water in reverse micelles of mixed surfactants

In this contribution, we attempt to correlate the change in water dynamics in a reverse micellar (RM) core caused by the modification of the interface by mixing an anionic surfactant, sodium bis(2-ethylhexyl) sulfosuccinate (AOT), and a nonionic surfactant, tetraethylene glycol monododecyl ether (Brij-30), at different proportions, and its consequent effect on the reactivity of water, measured by monitoring the solvolysis reaction of benzoyl chloride (BzCl). The dimension of the RM droplets at different mixing ratios of AOT and Brij-30 (X(Brij-30)) has been measured using dynamic light scattering (DLS) technique. The physical properties of the RM water have been determined using Fourier transform infrared spectroscopy (FTIR) and compressibility studies, which show that with increasing X(Brij-30), the water properties tend toward that of bulk-like water. The solvation dynamics, probed by coumarin 500 dye, gets faster with X(Brij-30). The rotational anisotropy studies along with a wobbling-in-cone analysis show that the probe experiences less restriction at higher X(Brij-30). The kinetics of the water-mediated solvolysis also gets faster with X(Brij-30). The increased rate of solvolysis has been correlated with the accelerated solvation dynamics, which is another consequence of surfactant headgroup-water interaction.     

Mixed micelles formed by n-octyl-beta-D-glucopyranoside and tetradecyltrimethylammonium bromide in aqueous media

Speed of sound, density, conductivity, and fluorescence spectroscopy experiments were run to analyze the mixed aggregation process of a nonionic-cationic surfactant system in aqueous media at 298.15 K. The mixed system comprises a nonionic surfactant, n-octyl-beta-D-glucopyranoside (OBG), and a cationic surfactant, tetradecyltrimethylammonium bromide (C14TAB), with 8 and 14 carbon atoms on the hydrophobic tails, respectively. From these data, the total and partial critical micellar concentrations, the total and partial aggregation numbers, apparent molar volumes and isentropic compressibilities, hydration numbers, and the corresponding changes in the latest properties due to the mixed aggregation process were determined. Pure and mixed micelles were analyzed from a geometrical point of view by determining the packing parameter of the aggregates. Furthermore, the experimental characterization of both the monomeric and micellar phases was completed with a theoretical study of the mixed micellization phenomena studied herein, by means of some of the most relevant theoretical models.     

Dispersion behavior of oleic acid in aqueous media: from micelles to emulsions

 Dispersion behavior of aqueous solutions containing oleic acid (RH), sodium oleate (R^-Na⁺), and NaCl was investigated by turbidity and dynamic light-scattering measurements. Changes of the size of scattering particles in solution composed of 1 mM oleic acid and 100 mM NaCl were traced as a function of the degree of ionization α, in terms of radius of the equivalent hydrodynamic sphere. Large associated micelles with a radius of 30 nm appeared by a slight decline of α and existed at α higher than 0.75. They were responsible for the three-phase equilibrium (solution, micelle and aggregated micelle, and acid–soap, (R^-Na⁺)₃RH) characterized by a constant pH of 9.75. The appearance of a new phase, (R^-Na⁺)₃RH, contributed to increase both the turbidity and averaged scattering particle size. As the breakdown of the three-phase equilibrium, radius of scattering particles increased significantly. Finally, oleic acid oil droplets were separated from aqueous phase at low α. When the system was buffered by tris(hydroxymethyl)aminomethane (Tris), scattering particles with a weight-averaged hydrodynamic radius of 75 nm existed in a wide range of α from 0.85 to 0.65. In Tris buffered solution, turbidity formation was induced by the increase in the number of aggregated particles. Received: 12 November 1996 Accepted: 4 April 1997     

Specific interactions improve the loading capacity of block copolymer micelles in aqueous media

Block copolymer micelles find application in many fields as nanocarriers, especially in drug delivery. We report herein that specific interactions between hydrophobic guest molecules and core-forming segments can significantly improve the loading capacity of polymeric micelles. High loading capacities (>100% weight/weight of polymer (w/wp)) were systematically observed for the encapsulation of probes containing weak carboxylic acid groups by micellar nanoparticles having poly[2-(dialkylamino)ethyl methacrylate] cores (i.e., particles whose cargo space exhibits antagonist weak base functions), as demonstrated by the incorporation of indomethacin (IND), ibuprofen (IBPF), and trans-3,5-bis(trifluoromethyl)cinnamic acid (F-CIN) into either poly(ethylene oxide)-b-poly[2-(diisopropylamino)ethyl methacrylate] (PEO-b-PDPA) or poly(glycerol monomethacrylate)-b-PDPA (PG2MA-b-PDPA) micelles. The esterification of IND yielding to a nonionizable IND ethyl ester derivative (IND-Et) caused an abrupt decrease in the micellar loading capacity down to 10-15% w/wp. Similar results were also obtained when IND was combined with nonionizable block copolymers such as PEO-b-polycaprolactone (PEO-b-PCL) and PEO-b-poly(glycidyl methacrylate) (PEO-b-PGMA). The existence of acid-base interactions between the solubilizate and the weak polybase block forming the micelle core was confirmed by 1H NMR measurements. However, the incorporation of high numbers of hydrophobic guest molecules inside polymeric micelles can provoke not only an increase in the hydrodynamic size (2RH) of the objects but also a substantial change in the morphology (transition from spheres to cylinders). The application of the Higuchi model showed that the probe release followed a diffusion-controlled mechanism, and diffusion coefficients (D) on the order of 10-18-10-17 cm2/s were determined for IND release from 1.0 mg/mL PEO113-b-PDPA50 + 100% w/wp IND. Probe release from micelles with weak polybase-based cores can also be triggered by changes in the solution pH.     

Physicochemical investigation of sulfonamide-derived compounds interacting with conventional cationic surfactants in aqueous media

The sulfonamide core in compounds is effective synthons, which offer exciting perspectives in chemotherapeutic and pharmacological research. In this study, we investigated the molecular interaction of potent sulfonamide derivatives (SDs), 2-benzenesulfonamido-3-methylbutyric acid (BSB) and tetraaquabis{3-methyl-2-[(phenylsulfonyl)amino]butanoate}copper(II) (Cu-BSB), with cationic surfactants, cetyltrimethyl ammonium bromide (CTAB) and ethylhexadecyl dimethyl ammonium bromide (EHDAB), using UV-visible spectroscopy and steady-state fluorescence measurements. Various mathematical models were applied to quantify the effect of cationic surfactants on physicochemical characteristics of BSB and Cu-BSB. These interactions were confirmed by estimating the partition coefficient (K_x), binding capacities (K_b), Stern-Volmer quenching constant (K_sv), and related Gibbs free energies (ΔG_b). The in-depth mechanism revealed that the binding mode in SD–surfactants combinational system is spontaneous and quenching exists in static mode initiated by ground-state complex formation. We believe that the true knowledge of host–guest interaction mechanisms concerning model membrane with entrapped moiety can help in better understanding of molecular recognition in related phospholipid membrane models.     

Local mobility and structure of cationic amphiphilic diblock copolymer micelles in aqueous solutions

The local mobility and organization of micelles formed by the cationic diblock copolymer PS-poly(N-ethyl-4-vinylpyridinium bromide) in dilute aqueous solutions is studied by spin-probe ESR spectroscopy. Micelles composed of a hydrophobic PS core and a lyophilizing polyelectrolyte corona are prepared by two methods: dialysis from a nonselective solvent and direct dispersion of the diblock copolymer in water under long-term heating. Velocity-sedimentation studies and static and dynamic light-scattering measurements show that the micelles obtained by dialysis have smaller mean hydrodynamic sizes and weight-average molecular masses and are less polydisperse than micelles prepared by direct dispersion. The ESR spectra of spin probes localized in micelles of both types are found to be identical. This finding suggests that their local structure is independent of the dispersion procedure and molecular-mass characteristics. Probes are localized in the outer layer of the PS core near the core/shell boundary, and their local mobility is a factor of ∼2 higher than the local mobility of probes in the phase of the solid PS. It is inferred that the structure of the outer layer of the PS core in micelles is looser than the structure of PS in the solid phase. The localization sites of spin probes are partially penetrated by water.     

Interactions between ethyl(hydroxyethyl) cellulose and lysine-based surfactants in aqueous media

In this work, the interaction between ethyl(hydroxyethyl) cellulose (EHEC) and three dimeric lysine-based surfactants of distinct chain length (C₆, C₈ and C₁₀) have been assessed and the system was evaluated in terms of its temperature-dependent gelling capacity. The viscosity profile depends on the specific surfactant, its concentration and temperature. The observed profiles reflected polymer–polymer associations at elevated temperatures and polymer-surfactant interactions, implying the formation of micellar-type associations. The systems induce gelation at higher temperatures. Longer chain-length surfactants induce gelation at lower concentrations due to their stronger tendency to self-assemble. The thermo-responsive gels showed gel strength generally lower than 20 Pa.sⁿ and a fractal dimension of 2.3–2.4, respectively, indicating the formation of soft gels comprising a tight and homogeneous network. The weakest gel was produced in the presence of the C₆ surfactant. 2D Small-Angle Light Scattering patterns showed a pronounced effect of temperature in terms of the evolution of large hydrophobic clusters, an event precluded when high concentrations of the longer chain surfactants were used.     

Binary interactions and salt-induced coalescence of spherical micelles of cationic surfactants from molecular dynamics simulations

A direct estimation of salt-mediated potential of mean force (PMF) between spherical micelles of cationic surfactants is obtained for the first time using molecular dynamics (MD) simulations. Coarse-grained (CG) potentials benchmarked in an earlier study [Langmuir, 2011, 27(11), 6628-6638] are used to model a binary system of cetyltrimethylammonium chloride (CTAC) surfactant micelles at varying concentrations of sodium chloride (NaCl) or sodium salicylate (NaSal). The shape and structure of micelles are not subject to external constraints. NaSal is significantly more efficient in screening the intermicelle repulsive interactions shown by the PMF compared to NaCl due to a stronger binding of salicylate counterions to the micelle corona. Upon contact with each other, the micelles coalesce in the presence of NaSal to form a cylindrical structure which is stabilized by the adsorbed salicylate anions. Comparison of the PMF with Derjaguin-Landau-Verwey-Overbeek (DLVO) potentials shows qualitative agreement, while the magnitude of PMF is significantly greater than that of the DLVO potentials. To understand this discrepancy, PMF is evaluated by turning off (a) long-ranged electrostatic interactions and (b) solvent polarizability. The above effects are shown to play an important role in determining the solvent-mediated and ion-correlated interactions between the two micelles, which are not explicitly captured by mean-field double layer theories such as DLVO.     

Synthesis and comparative behaviour study of fluorocarbon and hydrocarbon cationic surfactants in aqueous media

A series of perfluorinated cationic surfactants and their corresponding hydrocarbon ones whose general formula is C_nX_2n+1-C(O)NH-(CH₂)₃-N⁺Me₃, I⁻, with X = F, H and n = 9, 11, have been synthesized via two steps. Their aggregative and surface-active properties were studied in aqueous solution using tensiometry and conductimetry. The critical micelle concentrations and the molecular areas at the air/water interface of fluorinated surfactants are lower than those of their hydrocarbon homologues. Micellar aggregation numbers and geometric packing parameters have been investigated. The results indicated that fluorocarbon surfactants tend to form lamellar aggregates while the hydrocarbon ones associate into spherical aggregates.     

新型二肽类长链状化合物的分子动力学和量子化学研究

用分子动力学方法对5种新型肽类长链状化合物进行了构象研究,所得结果证明我们的构象搜索方法有效。分子L~3内的芳环堆积作用使整个分子具有特殊结构,这种结构特征可能使其具有特殊生物功能,该结果为药物分子设计提供了有用的信息。量子化学计算表明分子内形成的负电荷空穴,将使其易与受体结合。     

Light scattering study of solubilization of organic molecules by block copolymer micelles in aqueous media

Block copolymers, when dissolved in a selective solvent, form spherical micelles. These micelles can selectively solubilize organic molecules otherwise insoluble in the pure solvent. In this study, we report solubilization of organic molecules by styrene-methacrylic acid block copolymer micelles in aqueous buffers. A light scattering technique was developed to determine the extent of micellar solubilization. Our results indicate that the extent of micellar solubilization depends on the chemical nature of organic molecules, specifically, on the interactions between the organic compound and polystyrene. A thermodynamic model has been developed to describe micellar solubilization. The theoretical calculation agrees reasonably well with the experimental results for two micellar samples examined. ©1995 John Wiley & Sons, Inc.     

Sphere-to-rod transitions of nonionic surfactant micelles in aqueous solution modeled by molecular dynamics simulations

Control of the size and agglomeration of micellar systems is important for pharmaceutical applications such as drug delivery. Although shape-related transitions in surfactant solutions are studied experimentally, their molecular mechanisms are still not well understood. In this study, we use coarse-grained molecular dynamics simulations to describe micellar assemblies of pentaethylene glycol monododecyl ether (C(12)E(5)) in aqueous solution at different concentrations. The obtained size and aggregation numbers of the aggregates formed are in very good agreement with the available experimental data. Importantly, increase of the concentration leads to a second critical micelle concentration where a transition to rod-like aggregates is observed. This transition is quantified in terms of shape anisotropy, together with a detailed structural analysis of the micelles as a function of aggregation number.