Sample records for micelle aggregation number

  1. Determination of the aggregation number for micelles by isothermal titration calorimetry

    Olesen, Niels Erik; Holm, Rene; Westh, Peter


    Isothermal titration calorimetry (ITC) has previously been applied to estimate the aggregation number (n), Gibbs free energy (ΔG), enthalpy (ΔH) and entropy (ΔS) of micellization. However, some difficulties of micelle characterization by ITC still remain; most micelles have aggregation numbers...... > 4 and its mathematical implementation is therefore not straight-forward. It seems as if all of these difficulties can be traced back to the aggregation number. In this work a new principle of data quantification is derived which is easy to apply, interpret and will provide statistical reliable...... insight into optimal design of titration protocols for micelle characterization. By applying the new method, the aggregation number of sodium dodecyl sulphate and glycochenodeoxycholate was determined at concentrations around their critical micelle concentration (CMC)...

  2. Effect of compressed CO2 on the critical micelle concentration and aggregation number of AOT reverse micelles in isooctane.

    Chen, Jing; Zhang, Jianling; Han, Buxing; Feng, Xiaoying; Hou, Minqiang; Li, Wenjing; Zhang, Zhaofu


    The effect of compressed CO2 on the critical micelle concentration (cmc) and aggregation number of sodium bis-2-ethylhexylsulfosuccinate (AOT) reverse micelles in isooctane solution was studied by UV/Vis and fluorescence spectroscopy methods in the temperature range of 303.2-318.2 K and at different pressures or mole fractions of CO2 (X(CO2)). The capacity of the reverse micelles to solubilize water was also determined by direct observation. The standard Gibbs free energy (DeltaGo(m)), standard enthalpy (DeltaHo(m)), and standard entropy (DeltaSo(m)) for the formation of the reverse micelles were calculated by using the cmc data determined. It was discovered that the cmc versus X(CO2) curve and the DeltaGo(m) versus X(CO2) curve for a fixed temperature have a minimum, and the aggregation number and water-solubilization capacity of the reverse micelles reach a maximum at the X(CO2) value corresponding to that minimum. These results indicate that CO2 at a suitable concentration favors the formation of and can stabilize AOT reverse micelles. A detailed thermodynamic study showed that the driving force for the formation of the reverse micelles is entropy.

  3. Aggregation number-based degrees of counterion dissociation in sodium n-alkyl sulfate micelles.

    Lebedeva, Nataly V; Shahine, Antoine; Bales, Barney L


    Values of the degree of counterion dissociation, alpha, for sodium n-alkyl sulfate micelles, denoted by SN(c)S, where N(c) is the number of carbon atoms in the alkyl chain, are defined by asserting that the aggregation number, N, is dependent only on the concentration, C(aq), of counterions in the aqueous pseudophase. By using different combinations of surfactant and added salt concentrations to yield the same value of N, alpha can be determined, independent of the experimental method. Electron paramagnetic resonance measurements of the hyperfine spacings of two nitroxide spin probes, 16- and 5-doxylstearic acid methyl ester (16DSE and 5DSE, respectively), are employed to determine whether micelles from two samples have the same value of N to high precision. The EPR spectra are different for the two spin probes, but the values of alpha are the same, within experimental error, as they must be. In agreement with recent work on S12S and with prevailing thought in the literature, values of alpha are constant as a function of N. This implies that the value of alpha is constant whether the surfactant or added electrolyte concentrations are varied. Interestingly, alpha varies with chain length as follows: N(c) = 8, alpha = 0.42 +/- 0.03; N(c) = 9, alpha = 0.41 +/- 0.03; N(c) = 10, alpha = 0.35 +/- 0.02; N(c) = 11, alpha = 0.30 +/- 0.02 at 25 degrees C and N(c) = 13, alpha = 0.22 +/- 0.02; and N(c) = 14, alpha = 0.19 +/- 0.01 at 40 degrees C. A simple electrostatic theoretical description, based on the nonlinear Poisson-Boltzmann equation for the ion distribution around a charged sphere, was compared with the experimental results. The theory predicts values of alpha that are in reasonable agreement with experiment, nicely predicting the decrease of alpha as N(c) increases. However, the theory also predicts that, for a given value of N(c), alpha decreases as N increases. Moreover, this decrease is predicted to be different if N is increased by adding salt or by increasing

  4. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry

    Olesen, Niels Erik; Westh, Peter; Holm, René


    The aggregation number (n), thermodynamic potentials (ΔG, ΔH, ΔS) and critical micelle concentration (CMC) for 6 natural bile salts were determined on the basis of both original and previously published isothermal titration calorimetry (ITC) data. Different procedures to estimate parameters...

  5. Determination of thermodynamic potentials and the aggregation number for micelles with the mass-action model by isothermal titration calorimetry: A case study on bile salts.

    Olesen, Niels Erik; Westh, Peter; Holm, René


    The aggregation number (n), thermodynamic potentials (ΔG, ΔH, ΔS) and critical micelle concentration (CMC) for 6 natural bile salts were determined on the basis of both original and previously published isothermal titration calorimetry (ITC) data. Different procedures to estimate parameters of micelles with ITC were compared to a mass-action model (MAM) of reaction type: n⋅S⇌Mn. This analysis can provide guidelines for future ITC studies of systems behaving in accordance with this model such as micelles and proteins that undergo self-association to oligomers. Micelles with small aggregation numbers, as those of bile salts, are interesting because such small aggregates cannot be characterized as a separate macroscopic phase and the widely applied pseudo-phase model (PPM) is inaccurate. In the present work it was demonstrated that the aggregation number of micelles was constant at low concentrations enabling determination of the thermodynamic potentials by the MAM. A correlation between the aggregation number and the heat capacity was found, which implies that the dehydrated surface area of bile salts increases with the aggregation number. This is in accordance with Tanford's principles of opposing forces where neighbouring molecules in the aggregate are better able to shield from the surrounding hydrophilic environment when the aggregation number increases. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Micelle depletion-induced vs. micelle-mediated aggregation in nanoparticles

    Ray, D., E-mail:; Aswal, V. K. [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)


    The phase behavior anionic silica nanoparticle (Ludox LS30) with non-ionic surfactants decaethylene glycol monododecylether (C12E10) and cationic dodecyltrimethyl ammonium bromide (DTAB) in aqueous electrolyte solution has been studied by small-angle neutron scattering (SANS). The measurements have been carried out for fixed concentrations of nanoparticle (1 wt%), surfactants (1 wt%) and electrolyte (0.1 M NaCl). Each of these nanoparticle–surfactant systems has been examined for different contrast conditions where individual components (nanoparticle or surfactant) are made visible. It is observed that the nanoparticle-micelle system in both the cases lead to the aggregation of nanoparticles. The aggregation is found to be micelle depletion-induced for C12E10 whereas micelle-mediated aggregation for DTAB. Interestingly, it is also found that phase behavior of mixed surfactant (C12E10 + DTAB) system is similar to that of C12E10 (unlike DTAB) micelles with nanoparticles.

  7. Monitoring the aggregation of single casein micelles using fluorescence microscopy

    Bomholt, Julie; Moth-Poulsen, Kasper; Harboe, Marianne


    The aggregation of casein micelles (CMs) induced by milk-clotting enzymes is a process of fundamental importance in the dairy industry for cheese production; however, it is not well characterized on the nanoscale. Here we enabled the monitoring of the kinetics of aggregation between single CMs (30...

  8. Relaxation times and modes of disturbed aggregate distribution in micellar solutions with fusion and fission of micelles

    Zakharov, Anatoly I.; Adzhemyan, Loran Ts.; Shchekin, Alexander K., E-mail: [Department of Statistical Physics, Faculty of Physics, St. Petersburg State University, Ulyanovskaya 1, Petrodvoretz, St. Petersburg 198504 (Russian Federation)


    We have performed direct numerical calculations of the kinetics of relaxation in the system of surfactant spherical micelles under joint action of the molecular mechanism with capture and emission of individual surfactant molecules by molecular aggregates and the mechanism of fusion and fission of the aggregates. As a basis, we have taken the difference equations of aggregation and fragmentation in the form of the generalized kinetic Smoluchowski equations for aggregate concentrations. The calculations have been made with using the droplet model of molecular surfactant aggregates and two modified Smoluchowski models for the coefficients of aggregate-monomer and aggregate-aggregate fusions which take into account the effects of the aggregate size and presence of hydrophobic spots on the aggregate surface. A full set of relaxation times and corresponding relaxation modes for nonequilibrium aggregate distribution in the aggregation number has been found. The dependencies of these relaxation times and modes on the total concentration of surfactant in the solution and the special parameter controlling the probability of fusion in collisions of micelles with other micelles have been studied.

  9. Dissipative Particle Dynamics Study on Aggregation of MPEG- PAE-PLA Block Polymer Micelles Loading Doxorubicine

    杨楚芬; 孙尧; 章莉娟; 朱国典; 张灿阳; 钱宇


    To guide the molecular design of the pH-sensitive triblock amphiphilic polymer MPEG-PAE-PLA and the for- mula design of its doxorubicine (DOX)-loaded micelles, dissipative particle dynamics (DPD) simulations are em- ployed to investigate the aggregation behaviors of the DOX-loaded micelles. The simulation results showed that the aggregate morphologies of micelles and DOX distribution are influenced by degree of polymerization of blocks, and the proposed structure of polymer is MPEG44-PAE3-PLA4. With different contents of polymer or DOX, differ- ent aggregate morphologies of the micelles, like microsphere, spindle/column, reticulation or lamella are observed. To prepare the micro-spherical DOX-loaded micelles, the polymer content is proposed as 10%--15%, and the DOX content less than 10%.

  10. Complex coacervation core micelles. Colloidal stability and aggregation mechanism

    Burgh, van der S.; Keizer, de A.; Cohen Stuart, M.A.


    Complex coacervation core micelles were prepared with various polyelectrolytes and oppositely charged diblock copolymers. The diblock copolymers consist of a charged block and a water-soluble neutral block. Our experimental technique was dynamic light scattering in combination with titrations. At

  11. Steroidal Surfactants: Detection of Premicellar Aggregation, Secondary Aggregation Changes in Micelles, and Hosting of a Highly Charged Negative Substance.

    Barnadas-Rodríguez, Ramon; Cladera, Josep


    CHAPSO and CHAPS are zwitterionic surfactants derived from bile salts which are usually employed in protein purification and for the preparation of liposomes and bicelles. Despite their spread use, there are significant discrepancies on the critical concentrations that determine their aggregation behavior. In this work, we study the interaction between these surfactants with the negative fluorescent dye pyranine (HPTS) by absorbance, fluorescence, and infrared spectrometry to establish their concentration-dependent aggregation. For the studied surfactants, we detect three critical concentrations showing their concentration-dependent presence as a monomeric form, premicellar aggregates, micelles, and a second type of micelle in aqueous medium. The nature of the interaction of HPTS with the surfactants was studied using analogues of their tails and the negative bile salt taurocholate (TC) as reference for the sterol ring. The results indicate that the chemical groups involved are the hydroxyl groups of the polar face of the sterol ring and the sulfonate groups of the dye. This interaction causes not only the incorporation of the negative dye in CHAPSO and CHAPS micelles but also its association with their premicellar aggregates. Surprisingly, this hosting behavior for a negative charged molecule was also detected for the negative bile salt TC, bypassing, in this way, the electrostatic repulsion between the guest and the host.

  12. Enzymic Milk Coagulation: Casein Micelle Aggregation and Curd Formation

    McMahon, Donald J.


    Enzymic milk coagulation was monitored by measuring changes in curd firmness and apparent absorbance of undiluted milk. Detection of coagulation, visually or rheologically, occurred after the milk changes from a system of aggregating particles to an extended space network. This change was observed as a shoulder in apparent absorbance plots and coagulation time was defined as the critical point in the aggregation process analogously to non-linear condensation polymerization reactions. It corre...

  13. Selective phosphorylation of cationic polypeptide aggregated with phosphatidylserine/diacylglycerol/Ca2+/detergent mixed micelles by Ca(2+)-independent but not Ca(2+)-dependent protein kinase C isozymes.

    Mahoney, C W; Huang, K P


    Mixed micelles containing Nonidet P40 (NP-40) (829 microM or 4.8 mM), phosphatidylserine (PS) (14.5 or 8 mol%), and 1,2-diacylglycerol (DG) (0.5 or 1 mol%) when preincubated with protein kinase C (PKC) assay mixture containing cationic substrate and CaCl2 (400 microM) formed aggregates in a time-, temperature-, and substrate concentration-dependent manner with a t1/2 approximately 3-12 min (22 degrees C). Concomitant with the formation of these aggregates there was a substantial loss of substrate phosphorylation catalyzed by the Ca(2+)-dependent PKC alpha, beta, and gamma but not the Ca(2+)-independent PKC, delta and epsilon. All cationic PKC substrates tested, neurogranin peptide analog, neurogranin, and histone III-S, formed aggregates with PS/DG/NP-40/Ca2+ mixed micelles in a time-dependent fashion. The poly(cationic-anionic) PKC substrate protamine sulfate also forms aggregates with the mixed micelles in the presence of Ca2+, but without affecting the substrate phosphorylation by the kinase. Under similar conditions, but at 4 degrees C, neither aggregation nor loss of cationic substrate phosphorylation was observed. Another nonionic detergent, octyl glucoside, behaved similarly to NP-40. Phosphatidylinositol (PI) and phosphatidylglycerol like PS, were effective in forming aggregates with NP-40/cationic polypeptide/DG/Ca2+ as monitored by light scattering, yet without affecting substrate phosphorylation. Phosphorylation of cationic substrates by M-kinase, derived from trypsinized PKC beta, was also greatly diminished by the aggregation. In contrast, [3H]phorbol 12,13-dibutyrate binding to PKC beta was unaffected. Formation of the aggregates that were selectively utilized by the Ca(2+)-independent PKCs was dependent on the ratio of cationic substrate to the number of mixed micelles.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Micelles and aggregates of oxyethylated isononylphenols and their extraction properties near cloud point.

    Arkhipov, Victor P; Idiyatullin, Zhamil Sh; Potapova, Elisaveta F; Antzutkin, Oleg N; Filippov, Andrey V


    We used nuclear magnetic resonance (NMR) spectroscopy and dynamic light scattering (DLS) techniques to study the structural and dynamic properties of micellar solutions of nonionic surfactants of a homologous series of oxyethylated isononylphenols--C9H19C6H4O(C2H4O)(n)H, where n = 6, 8, 9, 10, or 12--in a wide range of temperatures, including cloud points. The radii of the micelles and aggregates, as well as their compositions at different concentrations of surfactant, were determined. Using aqueous phenol solutions as a model, we studied the process of cloud point extraction with oxyethylated isononylphenols.

  15. Fluorescence of aminofluoresceins as an indicative process allowing one to distinguish between micelles of cationic surfactants and micelle-like aggregates

    Mchedlov-Petrossyan, Nikolay O.; Cheipesh, Tatiana A.; Roshal, Alexander D.; Doroshenko, Andrey O.; Vodolazkaya, Natalya A.


    Among the vast set of fluorescein derivatives, the double charged R2- anions of aminofluoresceins are known to exhibit only low quantum yields of fluorescence, \\varphi . The \\varphi value becomes as high as that of the fluorescein dianion when the lone electron pair of the amino group is involved in a covalent bond. According to Munkholm et al (1990 J. Am. Chem. Soc. 112 2608-12), a much smaller increase in the emission intensity can be observed in the presence of surfactant micelles. However, all these observations refer to aqueous or alcoholic solvents. In this paper, we show that in the non-hydrogen bond donor (or ‘aprotic’) solvents DMSO and acetone, the quantum yields, φ, of the 4‧- (or 5‧)-aminofluorescein R2- species amount to 61-67% and approach that of fluorescein (φ  =  87%), whereas in water φ is only 0.6-0.8%. In glycerol, a solvent with an extremely high viscosity, the φ value is only 6-10%. We report on the enhancement of the fluorescence of the aminofluorescein dianions as an indicative process, which allows us to distinguish between the micelle-like aggregates of cationic dendrimers of low generation, common spherical surfactant micelles, and surfactant bilayers. Some of these colloidal aggregates partly restore the fluorescence of aminofluoresceins in aqueous media. By contrast, other positively charged micellar-like aggregates do not enhance the quantum yield of aminofluorescein R2- species. Results for several related systems, such as CTAB-coated SiO2 particles and reverse microemulsions, are briefly described, and the possible reasons for the observed phenomena are discussed.

  16. Polymerization of anionic wormlike micelles.

    Zhu, Zhiyuan; González, Yamaira I; Xu, Hangxun; Kaler, Eric W; Liu, Shiyong


    Polymerizable anionic wormlike micelles are obtained upon mixing the hydrotropic salt p-toluidine hydrochloride (PTHC) with the reactive anionic surfactant sodium 4-(8-methacryloyloxyoctyl)oxybenzene sulfonate (MOBS). Polymerization captures the cross-sectional radius of the micelles (approximately 2 nm), induces micellar growth, and leads to the formation of a stable single-phase dispersion of wormlike micellar polymers. The unpolymerized and polymerized micelles were characterized using static and dynamic laser light scattering, small-angle neutron scattering, 1H NMR, and stopped-flow light scattering. Stopped-flow light scattering was also used to measure the average lifetime of the unpolymerized wormlike micelles. A comparison of the average lifetime of unpolymerized wormlike micelles with the surfactant monomer propagation rate was used to elucidate the mechanism of polymerization. There is a significant correlation between the ratio of the average lifetime to the monomer propagation rate and the average aggregation number of the polymerized wormlike micelles.

  17. Micelles Hydrodynamics

    Svintradze, David V


    A micelle consists of monolayer of lipid molecules containing hydrophilic head and hydrophobic tail. These amphiphilic molecules in aqueous environment aggregate spontaneously into monomolecular layer held together due to hydrophobic effect by weak non-covalent forces. Micelles are flexible surfaces that show variety of shapes of different topology, but remarkably in mechanical equilibrium conditions they are spherical in shape. The shape and size of a micelle are functions of many variables such as lipid concentration, temperature, ionic strength, etc. Addressing the question, why the shape of micelles is sphere in mechanical equilibrium conditions, analytically proved to be a difficult problem. In the following paper we offer the shortest and elegant analytical proof of micelles spheroidal nature when they are thermodynamically equilibrated with solvent. The formalism presented in this paper can be readily extended to any homogenous surfaces, such are vesicles and membranes.

  18. Thermodynamics of Micellization of Surfactants of Low Aggregation Number: The Aggregation of Propranolol Hydrochloride.

    Mosquera; Ruso; Attwood; Jones; Prieto; Sarmiento


    The self-association of propranolol hydrochloride in aqueous solution has been studied as a function of temperature. The critical concentration (C*) and the degree of ionization (alpha) were determined by conductivity measurements at temperatures over the range 298.15 to 313.15 K. The enthalpy change on aggregation in water was measured by microcalorimetry. To calculate changes in the thermodynamic properties of aggregation the mass action model for high and low aggregation numbers was applied, the latter model giving better agreement between experimental and theoretical enthalpy changes. Copyright 1999 Academic Press.

  19. Detection of the critical micelle concentration of cationic and anionic surfactants based on aggregation-induced emission property of hexaphenylsilole derivatives


    We report a fluorescence "turn-on" method to detect the critical micelle concentration (CMC) of surfactants. This method works well for both cationic and anionic surfactants. It employs an unprecedented mechanism (aggregation-induced emission, or AIE) to determine the CMC values, and the results are consistent with the data obtained by the classical techniques. In addition, this method renders the convenient detection of the CMC values. Any large and professional instruments are unnecessary, instead, a portable UV lamp and an ultrasonic generator are enough to carry out the detection in an ordinary laboratory. Considering that micelles are interesting entities and have found applications in many important fields such as emulsion polymerization, template of nanosized materials synthesis, controllable drug delivery and macromolecular self-assembling. Our experimental results may offer a facile, sensitive and promising method to detect the formation of micelles constructed by the new amphiphilic molecules and macromolecules.

  20. Detection of the critical micelle concentration of cationic and anionic surfactants based on aggregation-induced emission property of hexaphenylsilole derivatives

    TANG Li; JIN JiaKe; ZHANG Shuang; MAO Yu; SUN JingZhi; YUAN WangZhang; ZHAO Hui; XU HaiPeng; QIN AnJun; TANG Ben Zhong


    We report a fluorescence "turn-on" method to detect the critical micelle concentration (CMC) of sur-factants. This method works well for both cationic and anionic surfactants. It employs an unprece-dented mechanism (aggregation-induced emission, or AIE) to determine the CMC values, and the re-suits are consistent with the data obtained by the classical techniques. In addition, this method renders the convenient detection of the CMC values. Any large and professional instruments are unnecessary, instead, a portable UV lamp and an ultrasonic generator are enough to carry out the detection in an ordinary laboratory. Considering that micelles are interesting entities and have found applications in many important fields such as emulsion polymerization, template of nanoeized materials synthesis, controllable drug delivery and macromolecular self-assembling. Our experimental results may offer a facile, sensitive and promising method to detect the formation of micelles constructed by the new amphiphilic molecules and macromolecules.

  1. Polar Solvents Trigger Formation of Reverse Micelles.

    Khoshnood, Atefeh; Firoozabadi, Abbas


    We use molecular dynamics simulations and molecular thermodynamics to investigate the formation of reverse micelles in a system of surfactants and nonpolar solvents. Since the early observation of reverse micelles, the question has been whether the existence of polar solvent molecules such as water is the driving force for the formation of reverse micelles in nonpolar solvents. In this work, we use a simple coarse-grained model of surfactants and solvents to show that a small number of polar solvent molecules triggers the formation of large permanent aggregates. In the absence of polar molecules, both the thermodynamic model and molecular simulations show that small aggregates are more populated in the solution and larger ones are less frequent as the system evolves over time. The size and shape of reverse micelles depend on the size of the polar core: the shape is spherical for a large core and ellipsoidal for a smaller one. Using the coarse-grained model, we also investigate the effect of temperature and surfactant tail length. Our results reveal that the number of surfactant molecules in the micelle decreases as the temperature increases, but the average diameter does not change because the size of the polar core remains invariant. A reverse micelle with small polar core attracts fewer surfactants when the tail is long. The uptake of solvent particles by a micelle of longer surfactant tail is less than shorter ones when the polar solvent particles are initially distributed randomly.


    Chuan-qun Huang; Chun-yan Hong; Cai-yuan Pan


    Amphiphilic block copolymers, poly(ethylene oxide)-b-poly(N-acryloxysuccinimide) (PEO-b-PNAS) with various molecular weights have been successfully synthesized by atom transfer radical polymerization (ATRP) of NAS using functionalized PEO (PEO-Br) as ATRP macroinitiator. The self-assembling of the block copolymers in water, which is a good solvent for PEO and a non-solvent for PNAS, yielded spherical core-shell micelles with PNAS as core and PEO as shell. The cross-linked reaction of oxysuccinimide in PNAS chains with ethylenediamine occurred in the core of micelles,and the core cross-linked micelles were formed. The flower-like and dendritic aggregates were formed by self-assembling of the core cross-linked micelles on the glass slides or silicon wafers. Longer PNAS block in the block copolymers and higher evaporation temperature formed bigger spherical particles. The optical microscope was used to follow the formation and growth of the flower-like aggregates from the colloidal solution and the main driving forces for the self-assembling are solution fluid and interactions between PEO chains.

  3. Statistical crystallography of surface micelle spacing

    Noever, David A.


    The aggregation of the recently reported surface micelles of block polyelectrolytes is analyzed using techniques of statistical crystallography. A polygonal lattice (Voronoi mosaic) connects center-to-center points, yielding statistical agreement with crystallographic predictions; Aboav-Weaire's law and Lewis's law are verified. This protocol supplements the standard analysis of surface micelles leading to aggregation number determination and, when compared to numerical simulations, allows further insight into the random partitioning of surface films. In particular, agreement with Lewis's law has been linked to the geometric packing requirements of filling two-dimensional space which compete with (or balance) physical forces such as interfacial tension, electrostatic repulsion, and van der Waals attraction.

  4. Thermodynamics of micelle formation in a water-alcohol solution of sodium tetradecyl sulfate

    Shilova, S. V.; Tret'yakova, A. Ya.; Barabanov, V. P.


    The effects of addition of ethanol and propan-1-ol on sodium tetradecyl sulfate micelle formation in an aqueous solution are studied via microprobe fluorescence microscopy and conductometry. The critical micelle concentration, quantitative characteristics of micelles, and thermodynamic parameters of micelle formation are determined. Addition of 5-15 vol % of ethanol or 5-10 vol % of propan-1-ol is shown to result in a lower critical micelle concentration than in the aqueous solution, and in the formation of mixed spherical micelles whose sizes and aggregation numbers are less than those for the systems without alcohol. The contribution from the enthalpy factor to the free energy of sodium tetradecyl sulfate micelle formation is found to dominate in mixed solvents, in contrast to aqueous solutions.

  5. Mixed micelles of 7,12-dioxolithocholic acid and selected hydrophobic bile acids: interaction parameter, partition coefficient of nitrazepam and mixed micelles haemolytic potential.

    Poša, Mihalj; Tepavčević, Vesna


    The formation of mixed micelles built of 7,12-dioxolithocholic and the following hydrophobic bile acids was examined by conductometric method: cholic (C), deoxycholic (D), chenodeoxycholic (CD), 12-oxolithocholic (12-oxoL), 7-oxolithocholic (7-oxoL), ursodeoxycholic (UD) and hiodeoxycholic (HD). Interaction parameter (β) in the studied binary mixed micelles had negative value, suggesting synergism between micelle building units. Based on β value, the hydrophobic bile acids formed two groups: group I (C, D and CD) and group II (12-oxoL, 7-oxoL, UD and HD). Bile acids from group II had more negative β values than bile acids from group I. Also, bile acids from group II formed intermolecular hydrogen bonds in aggregates with both smaller (2) and higher (4) aggregation numbers, according to the analysis of their stereochemical (conformational) structures and possible structures of mixed micelles built of these bile acids and 7,12-dioxolithocholic acid. Haemolytic potential and partition coefficient of nitrazepam were higher in mixed micelles built of the more hydrophobic bile acids (C, D, CD) and 7,12-dioxolithocholic acid than in micelles built only of 7,12-dioxolithocholic acid. On the other hand, these mixed micelles still had lower values of haemolytic potential than micelles built of C, D or CD. The mixed micelles that included bile acids: 12-oxoL, 7-oxoL, UD or HD did not significantly differ from the micelles of 7,12-dioxolithocholic acid, observing the values of their haemolytic potential.

  6. Calculations of critical micelle concentration by dissipative particle dynamics simulations: the role of chain rigidity.

    Lee, Ming-Tsung; Vishnyakov, Aleksey; Neimark, Alexander V


    Micelle formation in surfactant solutions is a self-assembly process governed by complex interplay of solvent-mediated interactions between hydrophilic and hydrophobic groups, which are commonly called heads and tails. However, the head-tail repulsion is not the only factor affecting the micelle formation. For the first time, we present a systematic study of the effect of chain rigidity on critical micelle concentration and micelle size, which is performed with the dissipative particle dynamics simulation method. Rigidity of the coarse-grained surfactant molecule was controlled by the harmonic bonds set between the second-neighbor beads. Compared to flexible molecules with the nearest-neighbor bonds being the only type of bonded interactions, rigid molecules exhibited a lower critical micelle concentration and formed larger and better-defined micelles. By varying the strength of head-tail repulsion and the chain rigidity, we constructed two-dimensional diagrams presenting how the critical micelle concentration and aggregation number depend on these parameters. We found that the solutions of flexible and rigid molecules that exhibited approximately the same critical micelle concentration could differ substantially in the micelle size and shape depending on the chain rigidity. With the increase of surfactant concentration, primary micelles of more rigid molecules were found less keen to agglomeration and formation of nonspherical aggregates characteristic of flexible molecules.

  7. Enzyme recovery using reversed micelles.

    Dekker, M.


    The objective of this study was to develop a liquid-liquid extraction process for the recovery of extracellular enzymes. The potentials of reaching this goal by using reversed micelles in an organic solvent have been investigated.Reversed micelles are aggregates of surfactant molecules containing an

  8. CHARMM-GUI micelle builder for pure/mixed micelle and protein/micelle complex systems.

    Cheng, Xi; Jo, Sunhwan; Lee, Hui Sun; Klauda, Jeffery B; Im, Wonpil


    Micelle Builder in CHARMM-GUI, , is a web-based graphical user interface to build pure/mixed micelle and protein/micelle complex systems for molecular dynamics (MD) simulation. The robustness of Micelle Builder is tested by simulating four detergent-only homogeneous micelles of DHPC (dihexanoylphosphatidylcholine), DPC (dodecylphosphocholine), TPC (tetradecylphosphocholine), and SDS (sodium dodecyl sulfate) and comparing the calculated micelle properties with experiments and previous simulations. As a representative protein/micelle model, Pf1 coat protein is modeled and simulated in DHPC micelles with three different numbers of DHPC molecules. While the number of DHPC molecules in direct contact with Pf1 protein converges during the simulation, distinct behavior and geometry of micelles lead to different protein conformations in comparison to that in bilayers. It is our hope that CHARMM-GUI Micelle Builder can be used for simulation studies of various protein/micelle systems to better understand the protein structure and dynamics in micelles as well as distribution of detergents and their dynamics around proteins.

  9. A small-angle neutron scattering study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles.

    Bastiat, Guillaume; Grassl, Bruno; Borisov, Oleg; Lapp, Alain; François, Jeanne


    Mixed micelle of protonated or deuterated sodium dodecyl sulfate (SDS and SDSd25, respectively) and poly(propylene oxide) methacrylate (PPOMA) are studied by small-angle neutron scattering (SANS). In all the cases the scattering curves exhibit a peak whose position changes with the composition of the system. The main parameters which characterize mixed micelles, i.e., aggregation numbers of SDS and PPOMA, geometrical dimensions of the micelles and degree of ionisation are evaluated from the analysis of the SANS curves. The position q(max) of the correlation peak can be related to the average aggregation numbers of SDS-PPOMA and SDSd25-PPOMA mixed micelles. It is found that the aggregation number of SDS decreases upon increasing the weight ratio PPOMA/SDS (or SDSd25). The isotopic combination, which uses the "contrast effect" between the two micellar systems, has allowed us to determine the mixed micelle composition. Finally, the SANS curves were adjusted using the RMSA for the structure factor S(q) of charged spherical particles and the form factor P(q) of spherical core-shell particle. This analysis confirms the particular core-shell structure of the SDS-PPOMA mixed micelle, i.e., a SDS "core" micelle surrounded by the shell formed by PPOMA macromonomers. The structural parameters of mixed micelles obtained from the analysis of the SANS data are in good agreement with those determined previously by conductimetry and fluorescence studies.

  10. New surfactant phosphine ligands and platinum(II) metallosurfactants. Influence of metal coordination on the critical micelle concentration and aggregation properties.

    Parera, Elisabet; Comelles, Francesc; Barnadas, Ramon; Suades, Joan


    We have prepared the first platinum(II) metallosurfactants from a new family of linear surfactant phosphines Ph(2)P(CH(2))(n)SO(3)Na {1 (n = 2), 2 (n = 6), and 3 (n = 10)}, which were synthesized by reaction between the halosulfonates X(CH(2))(n)SO(3)Na and sodium diphenylphosphide. The metallosurfactants cis-[PtCl(2)L(2)] (L = 1-3) were obtained after reaction between the phosphines and PtCl(2) in dimethylsulfoxide. All compounds were fully characterized by the usual methods {NMR ((1)H, (13)C, (31)P, (195)Pt), IR, MS-ESI and HRMS}. By exploring the surfactant properties of phosphines 1-3 and their respective platinum metallosurfactants cis-[PtCl(2)L(2)] (L = 1-3) through surface tension measurements, dynamic light scattering spectroscopy, and cryo-TEM microscopy, we were able to analyze the influence of the metal coordination on the critical micelle concentration (cmc) and the aggregation properties. The cmc values of platinum metallosurfactants were considerably lower than those obtained for the free phosphines 1-3. This behavior could be understood by an analogy between the structure of cis-[PtCl(2)L(2)] complexes and bolaform surfactants. The calculated values of area per molecule also showed different tendencies between 1-3 and cis-[PtCl(2)L(2)] complexes, which could be explained on the basis of the possible conformations of these compounds in the air-water interface. The study of aggregates by dynamic light scattering spectroscopy and cryo-TEM microscopy showed the formation of spherical disperse medium size vesicles in all cases. However, substantial differences were observed between the three free phosphines (the population of micellar aggregates increased with long chain length) and also between phosphines and their respective metallosurfactants.

  11. Micelle structural studies on oil solubilization by a small-angle neutron scattering

    Putra, Edy Giri Rachman [Neutron Science Division, HANARO Center, Korea Atomic Energy Research Institute (KAERI), 1045 Daedok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Neutron Scattering Laboratory, National Nuclear Energy Agency of Indonesia (BATAN), Gedung 40 Kawasan Puspiptek Serpong, Tangerang 15314 (Indonesia)], E-mail:; Seong, Baek Seok [Neutron Science Division, HANARO Center, Korea Atomic Energy Research Institute (KAERI), 1045 Daedok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of); Ikram, Abarrul [Neutron Scattering Laboratory, National Nuclear Energy Agency of Indonesia (BATAN), Gedung 40 Kawasan Puspiptek Serpong, Tangerang 15314 (Indonesia)


    A small-angle neutron scattering (SANS) technique was applied to reveal the micelle structural changes. The micelle structural changes of 0.3 M sodium dodecyl sulfate (SDS) concentration by addition of various oil, i.e. n-hexane, n-octane, and n-decane up to 60% (v/v) have been investigated. It was found that the size, aggregation number and the structures of the micelles changed exhibiting that the effective charge on the micelle decreases with an addition of oil. There was a small increase in minor axis of micelle while the correlation peak shifted to a lower momentum transfer Q and then to higher Q by a further oil addition.

  12. Effect of concentration on surfactant micelle shapes--A molecular dynamics study

    GAO Jian; GE Wei; LI Jinghai


    Many aspects of the behavior of surfactants have not been well understood due to the coupling of many different mechanisms. Computer simulation is, therefore, attractive in the sense that it can explore the effect of different mechanisms separately. In this paper, the shapes, structures and sizes of sodium dodecylbenzenesulfonate (SDBS) micelles under different concentrations in an oil/water mixture were studied via molecular dynamics (MD) simulations using a simplified atomistic model which basically maintains the hydrophile and lipophile properties of the surfactant molecules. Above the critical micellar concentration (cmc), surfactant molecules aggregate spontaneously to form a wide variety of assemblies, from spherical to rodlike, wormlike and bilayer micelles. Changes in their ratios of the principle moments of inertia (g1/g3, g2/g3) indicated the transition of micelle shapes at different concentrations. The aggregation number of micelle is found to have a power-law dependence on surfactant concentration.

  13. Study of sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles.

    Bastiat, Guillaume; Grassl, Bruno; Khoukh, Abdel; François, Jeanne


    Sodium dodecyl sulfate (SDS)-poly(propylene oxide) methacrylate (PPOMA) (of molecular weight M(w) = 434 g x mol(-1)) mixtures have been studied using conductimetry, static light scattering, fluorescence spectroscopy, and 1H NMR. It has been shown that SDS and PPOMA form mixed micelles, and SDS and PPOMA aggregation numbers, N(ag SDS) and N(ag PPOMA), have been determined. Total aggregation numbers of the micelles (N(ag SDS) + N(ag PPOMA)) and those of SDS decrease upon increasing the weight ratio R = PPOMA/SDS. Localization of PPOMA inside the mixed micelles is considered (i) using 1H NMR to localize the methacrylate function at the hydrophobic core-water interface and (ii) by studying the SDS-PPO micellar system (whose M(w) = 400 g x mol(-1)). Both methods have indicated that the PPO chain of the macromonomer is localized at the SDS micelle surface. Models based on the theorical prediction of the critical micellar concentration of mixed micelles and structural model of swollen micelles are used to confirm the particular structure proposed for the SDS-PPOMA system, i.e., the micelle hydrophobic core is primarily composed of the C12 chains of the sodium dodecyl sulfate, the hydrophobic core-water interface is made up of the SDS polar heads as well as methacrylate functions of the PPOMA, the PPO chains of the macromonomer are adsorbed preferentially on the surface, i.e., on the polar heads of the SDS.

  14. Tannin-assisted aggregation of natively unfolded proteins

    Zanchi, D.; Narayanan, T.; Hagenmuller, D.; Baron, A.; Guyot, S.; Cabane, B.; Bouhallab, S.


    Tannin-protein interactions are essentially physical: hydrophobic and hydrogen-bond-mediated. We explored the tannin-assisted protein aggregation on the case of β-casein, which is a natively unfolded protein known for its ability to form micellar aggregates. We used several tannins with specified length. Our SAXS results show that small tannins increase the number of proteins per micelle, but keeping their size constant. It leads to a tannin-assisted compactization of micelles. Larger tannins, with linear dimensions greater than the crown width of micelles, lead to the aggregation of micelles by a bridging effect. Experimental results can be understood within a model where tannins are treated as effective enhancers of hydrophobic attraction between specific sites in proteins.

  15. Complex coacervate core micelles from iron-based coordination polymers.

    Wang, Junyou; de Keizer, Arie; Fokkink, Remco; Yan, Yun; Cohen Stuart, Martien A; van der Gucht, Jasper


    Complex coacervate core micelles (C3Ms) from cationic poly(N-methyl-2-vinyl-pyridinium iodide)-b-poly(ethylene oxide) (P2MVP(41)-b-PEO(205)) and anionic iron coordination polymers are investigated in the present work. Micelle formation is studied by light scattering for both Fe(II)- and Fe(III)-containing C3Ms. At the stoichiometric charge ratio, both Fe(II)-C3Ms and Fe(III)-C3Ms are stable for at least 1 week at room temperature. Excess of iron coordination polymers has almost no effect on the formed Fe(II)-C3Ms and Fe(III)-C3Ms, whereas excess of P2MVP(41)-b-PEO(205) copolymers in the solution can dissociate the formed micelles. Upon increasing salt concentration, the scattering intensity decreases. This decrease is due to both a decrease in the number of micelles (or an increase in CMC) and a decrease in aggregation number. The salt dependence of the CMC and the aggregation number is explained using a scaling argument for C3M formation. Compared with Fe(II)-C3Ms, Fe(III)-C3Ms have a lower CMC and a higher stability against dissociation by added salt.

  16. Small angle neutron scattering studies of mixed micelles of sodium cumene sulphonate with cetyl trimethylammonium bromide and sodium dodecyl sulphate

    K V Padalkar; V G Gaikar; V K Aswal


    The aqueous solutions of sodium cumene sulphonate (NaCS) and its mixtures with each of cetyl trimethylammonium bromide (CTAB) and sodium dodecyl sulphate (SDS) are characterized by small angle neutron scattering (SANS). NaCS when added to CTAB solution leads to the formation of long rod-shaped micelles with a dramatic increase in the CTAB aggregation number. Its addition to SDS on the other hand results in the formation of smaller mixed micelles where part of SDS molecules in the micelle is replaced by NaCS molecules.

  17. Polymer micelles with hydrophobic core and ionic amphiphilic corona. 1. Statistical distribution of charged and nonpolar units in corona.

    Lysenko, Evgeny A; Kulebyakina, Alevtina I; Chelushkin, Pavel S; Rumyantsev, Artem M; Kramarenko, Elena Yu; Zezin, Alexander B


    Polymer micelles with hydrophobic polystyrene (PS) core and ionic amphiphilic corona from charged N-ethyl-4-vinylpyridinium bromide (EVP) and uncharged 4-vinylpyridine (4VP) units spontaneously self-assembled from PS-block-poly(4VP-stat-EVP) macromolecules in mixed dimethylformamide/methanol/water solvent. The fraction of statistically distributed EVP units in corona-forming block is β = [EVP]/([EVP]+[4VP]) = 0.3-1. Micelles were transferred into water via dialysis technique, and pH was adjusted to 9, where 4VP is insoluble. Structural characteristics of micelles were investigated both experimentally and theoretically as a function of corona composition β. Methods of dynamic and static light scattering, electrophoretic mobility measurements, sedimentation velocity, transmission electron microscopy, and UV spectrophotometry were applied. All micelles possessed spherical morphology. The aggregation number, structure, and electrophoretic mobility of micelles changed in a jumplike manner near β ~ 0.6-0.75. Below and above this region, micelle characteristics were constant or insignificantly changed upon β. Theoretical dependencies for micelle aggregation number, corona dimensions, and fraction of small counterions outside corona versus β were derived via minimization the micelle free energy, taking into account surface, volume, electrostatic, and elastic contributions of chain units and translational entropy of mobile counterions. Theoretical estimations also point onto a sharp structural transition at a certain corona composition. The abrupt reorganization of micelle structure at β ~ 0.6-0.75 entails dramatic changes in micelle dispersion stability in the presence of NaCl or in the presence of oppositely charged polymeric (sodium polymethacrylate) or amphiphilic (sodium dodecyl sulfate) complexing agents.

  18. Nanostructure of PEO-polyurethane-PEO triblock copolymer micelles in water.

    Caba, Beth L; Zhang, Qian; Carroll, Matthew R J; Woodward, Robert C; St Pierre, Timothy G; Gilbert, Elliot P; Riffle, Judy S; Davis, Richey M


    Novel hydrophilic triblock copolymers which form micelles in aqueous solution were studied by static and dynamic light scattering (SLS and DLS), small angle neutron scattering (SANS) and densitometry. The polymers were symmetric A-B-A block copolymers having two poly(ethylene oxide) (PEO) tail blocks and a polyurethane (PU) center segment that contained pendant carboxylic acids. The aggregation number of the micelles decreased with increasing PEO mass content. When attempting to fit the SANS data it was found that no single model was suitable over the entire range of block lengths and PEO mass concentrations investigated here. For the polymer with the highest aggregation number, the data were fitted with a triblock model consisting of a homogeneous core with a corona of non-interacting Gaussian chains for which only two free parameters were required: the radius of the core and the radius of gyration of the corona. In this case, the core was found to be effectively dry. At lower aggregation numbers, a star polymer model generated significantly better fits, suggesting the absence of any identifiable central core structure. Good agreement was found between the sizes measured by DLS, SANS and theoretical predictions of micelle size from a density distribution theory. These results show that when significant changes in aggregation number occur, the nanostructure of the micelle can change substantially even for polymers that are remarkably similar. Copyright 2009 Elsevier Inc. All rights reserved.

  19. Applications of micelle enhancement in luminescence-based analysis.

    Alarfaj, Nawal A; El-Tohamy, Maha F


    Micelles are self-assembled aggregates that arrange themselves into spheres in aqueous media. When the surfactant concentration reaches the critical micelle concentration, extensive aggregation of the surfactant monomers occurs to form micelles. A micelle has both a hydrophilic and a hydrophobic part. This allows them to form a spherical shape and for their glycolipid and phospholipid components to form lipid bilayers. The importance of micelles is increasing because of their wide analytical applications. Recently, colloidal carrier systems have received much attention in the field of analytical chemistry, especially in luminescence enhancement applications.

  20. Stability of complex coacervate core micelles containing metal coordination polymer.

    Yan, Yun; de Keizer, Arie; Cohen Stuart, Martien A; Drechsler, Markus; Besseling, Nicolaas A M


    We report on the stability of complex coacervate core micelles, i.e., C3Ms (or PIC, BIC micelles), containing metal coordination polymers. In aqueous solutions these micelles are formed between charged-neutral diblock copolymers and oppositely charged coordination polymers formed from metal ions and bisligand molecules. The influence of added salt, polymer concentration, and charge composition was investigated by using light scattering and cryo-TEM techniques. The scattering intensity decreases strongly with increasing salt concentration until a critical salt concentration beyond which no micelles exist. The critical micelle concentration increases almost exponentially with the salt concentration. From the scattering results it follows that the aggregation number decreases with the square root of the salt concentration, but the hydrodynamic radius remains constant or increases slightly. It was concluded that the density of the core decreases with increasing ionic strength. This is in agreement with theoretical predictions and is also confirmed by cryo-TEM measurements. A complete composition diagram was constructed based on the composition boundaries obtained from light scattering titrations.

  1. Size And Shape of Detergent Micelles Determined By Small-Angle X-Ray Scattering

    Lipfert, Jan; Columbus, Linda; Chu, Vincent B.; Lesley, Scott A.; Doniach, Sebastian; /Stanford U., Phys. Dept. /Stanford U., Appl. Phys. Dept. /SLAC, SSRL /Pasteur Inst., Paris /Scripps Res. Inst. /Novartis Res. Found.


    We present a systematic analysis of the aggregation number and shape of micelles formed by nine detergents commonly used in the study of membrane proteins. Small-angle X-ray scattering measurements are reported for glucosides with 8 and 9 alkyl carbons (OG/NG), maltosides and phosphocholines with 10 and 12 alkyl carbons (DM/DDM and FC-10/FC-12), 1,2-dihexanoyl-sn-glycero-phosphocholine (DHPC), 1-palmitoyl-2-hydroxy-sn-glycero-3-[phospho-rac-(1-glycerol)] (LPPG), and 3-[(3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS). The SAXS intensities are well described by two-component ellipsoid models, with a dense outer shell corresponding to the detergent head groups and a less electron dense hydrophobic core. These models provide an intermediate resolution view of micelle size and shape. In addition, we show that Guinier analysis of the forward scattering intensity can be used to obtain an independent and model-free measurement of the micelle aggregation number and radius of gyration. This approach has the advantage of being easily generalizable to protein-detergent complexes, where simple geometric models are inapplicable. Furthermore, we have discovered that the position of the second maximum in the scattering intensity provides a direct measurement of the characteristic head group-head group spacing across the micelle core. Our results for the micellar aggregation numbers and dimensions agree favorably with literature values as far as they are available. We de novo determine the shape of FC-10, FC-12, DM, LPPG, and CHAPS micelles and the aggregation numbers of FC-10 and OG to be ca. 50 and 250, respectively. Combined, these data provide a comprehensive view of the determinants of micelle formation and serve as a starting point to correlate detergent properties with detergent-protein interactions.

  2. Supercritical fluid reverse micelle separation

    Fulton, John L.; Smith, Richard D.


    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W.sub.o that determines the maximum size of the reverse micelles. The maximum ratio W.sub.o of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions.

  3. Supercritical fluid reverse micelle separation

    Fulton, J.L.; Smith, R.D.


    A method of separating solute material from a polar fluid in a first polar fluid phase is provided. The method comprises combining a polar fluid, a second fluid that is a gas at standard temperature and pressure and has a critical density, and a surfactant. The solute material is dissolved in the polar fluid to define the first polar fluid phase. The combined polar and second fluids, surfactant, and solute material dissolved in the polar fluid is maintained under near critical or supercritical temperature and pressure conditions such that the density of the second fluid exceeds the critical density thereof. In this way, a reverse micelle system defining a reverse micelle solvent is formed which comprises a continuous phase in the second fluid and a plurality of reverse micelles dispersed in the continuous phase. The solute material is dissolved in the polar fluid and is in chemical equilibrium with the reverse micelles. The first polar fluid phase and the continuous phase are immiscible. The reverse micelles each comprise a dynamic aggregate of surfactant molecules surrounding a core of the polar fluid. The reverse micelle solvent has a polar fluid-to-surfactant molar ratio W, which can vary over a range having a maximum ratio W[sub o] that determines the maximum size of the reverse micelles. The maximum ratio W[sub o] of the reverse micelle solvent is then varied, and the solute material from the first polar fluid phase is transported into the reverse micelles in the continuous phase at an extraction efficiency determined by the critical or supercritical conditions. 27 figures.

  4. Phospholipid containing mixed micelles. Characterization of diheptanoyl phosphatidylcholine (DHPC) and sodium dodecyl sulfate and DHPC and dodecyl trimethylammonium bromide.

    Ranganathan, Radha; Vautier-Giongo, Carolina; Bakshi, Mandeep Singh; Bales, Barney L; Hajdu, Joseph


    Mixed micelles of l,2-diheptanoyl-sn-grycero-3-phosphocholine (DHPC) with ionic detergents were prepared to develop well characterized substrates for the study of lipolytic enzymes. The aggregates that formed on mixing DHPC with the anionic surfactant sodium dodecyl sulfate (SDS) and with the positively charged dodecyl trimethylammonium bromide (DTAB) were investigated using time-resolved fluorescence quenching (TRFQ) to determine the aggregation numbers and bimolecular collision rates, and electron spin resonance (ESR) to measure the hydration index and microviscosity of the micelles at the micelle-water interface. Mixed micelles between the phospholipid and each of the detergents formed in all compositions, yielding interfaces with varying charge, hydration, and microviscosity. Both series of micelles were found to be globular up to 0.7 mole fraction of DHPC, while the aggregation numbers varied within the same concentration range of the components less than 15%. Addition of the zwitterionic phospholipid component increased the degree of counterion dissociation as measured by the quenching of the fluorescence of pyrene by the bromide ions bound to DHPC/DTAB micelles, showing that at 0.6 mole fraction of DHPC 80% of the bromide ions are dissociated from the micelles. The interface water concentration decreased significantly on addition of DHPC to each detergent. For combined phospholipid and detergent concentration of 50 mM the interface water concentration decreased, as measured by ESR of the spin-probes, from 38.5 M/L of interface volume in SDS alone to 9 M/L when the phospholipid was present at 0.7 mole fraction. Similar addition of DHPC to DTAB decreased the interfacial water concentration from 27 M/L to 11 M/L. Determination of the physicochemical parameters of the phospholipid containing mixed micelles here presented are likely to provide important insight into the design of assay systems for kinetic studies of phospholipid metabolizing enzymes.

  5. Small-angle neutron scattering study of aggregate structures of multi-headed pyridinium surfactants in aqueous solution

    J Haldar; V K Aswal; P S Goyal; S Bhattacharya


    The aggregate structures of a set of novel single-chain surfactants bearing one, two and three pyridinium headgroups have been studied using small-angle neutron scattering (SANS). It is found that the nature of aggregate structures of these cationic surfactants depend on the number of headgroups present in the surfactants. The single-headed pyridinium surfactant forms the lamellar structure, whereas surfactants with double and triple headgroups form micelles in water. The aggregates shrink in size with increase in the number of headgroups in the surfactants. The aggregation number () continually decreases and the fractional charge () increases with more number of headgroups on the surfactants. The semimajor axis () and semiminor axis ( = ) of the micelle also decrease with the increase in the number of headgroups in the surfactants. This indicates that hydrocarbon chains in such micelles prepared from multiheaded surfactants adopt bent conformation and no longer stay in extended conformation.

  6. Determination of micellar aggregation numbers of Gemini surfactants%Gemini阳离子表面活性剂胶束聚集数的测定

    倪人捷; 黄煜; 姚成


    以芘为荧光探针,十六烷基氯化吡啶为猝灭剂,用芘饱和水溶液配制浓度范围为0.10 ~2.40 mmol/L的系列Gemini阳离子表面活性剂溶液,用稳态荧光探针法测定了该系列表面活性剂的临界胶束浓度CMC与胶束聚集数N_m.实验结果表明:该方法测定的CMC值与电导率法测定的CMC值相当;选择猝灭剂浓度为0.20~0.50 mmol/L时,所测得的表面活性剂胶束聚集数基本不变;当表面活性剂16-X-16浓度为4~9倍CMC时,胶束聚集数随表面活性剂浓度增大而线性增大;利用外推法得到的该表面活性剂临界胶束聚集数约为亲油基同碳数的CTAB临界胶束聚集数的一半.%The critical micelle concentration (CMC) and micellar aggregation numbers of series of cationic Gemini surfactants are determined by steady-state fluorescence probe method in which py-rene was used as a fluorescence probe and cetylpyridinium chloride as a quencher. The experimental results indicate that the CMC values are basically in agreement with the values determined by conductivity method, the aggregation numbers of this series cationic Gemini surfactants are essentially constant when the concentrations of the quencher are in 0. 20 to 0. 50 mmol/L. The aggregation numbers of the Gemini surfactant(16-X-16) increases linearly with the increase of surfactant concentration in the range of 4 to 9 times of CMC. The critical micellar aggregation numbers obtained by extrapolation method are half of the CTAB's(cetyltrimethylammonium bromide) which is hydropho-bic with the same carbon number.

  7. Passage number affects the pluripotency of mouse embryonic stem cells as judged by tetraploid embryo aggregation.

    Li, Xiang-Yun; Jia, Qing; Di, Ke-Qian; Gao, Shu-Min; Wen, Xiao-Hui; Zhou, Rong-Yan; Wei, Wei; Wang, Li-Ze


    The aim of this study was to determine whether the number of passages affected the developmental pluripotency of embryonic stem (ES) cells as measured by the attainment of adult fertile mice derived from embryonic stem (ES) cell/tetraploid embryo complementation. Thirty-six newborns were produced by the aggregation of tetraploid embryos and hybrid ES cells after various numbers of passages. These newborns were entirely derived from ES cells as judged by microsatellite DNA, coat-color phenotype, and germline transmission. Although 15 survived to adulthood, 17 died of respiratory failure, and four were eaten by their foster mother. From the 15 mice that reached adulthood and that could reproduce, none arose from ES cells at passage level 15 or more. All 15 arose from cells at passages 3-11. Our results demonstrate that the number of passages affects the developmental pluripotency of ES cells.

  8. The critical micelle concentration of tetraethylammonium perfluorooctylsulfonate in water.

    López-Fontán, José L; González-Pérez, Alfredo; Costa, Julian; Ruso, Juan M; Prieto, Gerardo; Schulz, Pablo C; Sarmiento, Félix


    The aggregation characteristics of tetraethylammonium perfluorooctylsulfonate in water were studied by several techniques: conductivity, pH, ion-selective electrodes, and surface tension. It was concluded that the aggregation process is gradual and starts with the formation of oligomers such as ion pairs that grow to give spherical micelles, which become wormlike with increasing concentration. Because of the size and hydrophobicity of the counterion, micelles quickly increase in ionization degree up to about 0.5. Differences among different critical micelle concentration values in the literature are explained on the basis of the gradual formation of micelles.

  9. Bending energetics of tablet-shaped micelles: a novel approach to rationalize micellar systems.

    Bergström, L Magnus


    A novel approach to rationalize micellar systems is expounded in which the structural behavior of tablet-shaped micelles is theoretically investigated as a function of the three bending elasticity constants: spontaneous curvature (H0), bending rigidity (k(c)), and saddle-splay constant (k(c)). As a result, experimentally accessible micellar properties, such as aggregation number, length-to-width ratio, and polydispersity, may be related to the different bending elasticity constants. It is demonstrated that discrete micelles or connected cylinders form when H0 > 1/4xi, where xi is the thickness of a surfactant monolayer, whereas various bilayer structures are expected to predominate when H0 bending rigidity is lowered, approaching the critical point at k(c) = 0, whereas monodisperse globular micelles (small length-to-width ratio) are expected to be present at large k(c) values. The spontaneous curvature mainly determines the width of tablet-shaped or ribbonlike micelles, or the radius of disklike micelles, whereas the saddle-splay constant primarily influences the size but not the shape of the micelles.

  10. Electrical conductivity study on micelle formation of long-chain imidazolium ionic liquids in aqueous solution.

    Inoue, Tohru; Ebina, Hayato; Dong, Bin; Zheng, Liqiang


    Electrical conductivity was measured for aqueous solutions of long-chain imidazolium ionic liquids (IL), 1-alkyl-3-methylimidazolium bromides with C(12)-C(16) alkyl chains. The break points appeared in specific conductivity (kappa) vs concentration (c) plot indicates that the molecular aggregates, i.e., micelles, are formed in aqueous solutions of these IL species. The critical micelle concentration (cmc) determined from the kappa vs c plot is somewhat lower than those for typical cationic surfactants, alkyltrimethylammonium bromides with the same hydrocarbon chain length. The electrical conductivity data were analyzed according to the mixed electrolyte model of micellar solution, and the aggregation number, n, and the degree of counter ion binding, beta, were estimated. The n values of the present ILs are somewhat smaller than those reported for alkyltrimethylammonium bromides, which may be attributed to bulkiness of the cationic head group of the IL species. The thermodynamic parameters for micelle formation of the present ILs were estimated using the values of cmc and beta as a function of temperature. The contribution of entropy term to the micelle formation is superior to that of enthalpy term below about 30 degrees C, and it becomes opposite at higher temperature. This coincides with the picture drawn for the micelle formation of conventional ionic surfactants.

  11. Casein micelle structure: a concise review

    Chanokphat Phadungath


    Full Text Available Milk is a complex biological fluid with high amount of proteins, lipid and minerals. The function of milk is to supply nutrients such as essential amino acids required for the growth of the newborn. In addition, due to the importance of casein and casein micelles for the functional behavior of dairy products, the nature and structure of casein micelles have been studied extensively. However, the exact structure of casein micelles is still under debate. Various models for casein micelle structure have been proposed. Most of the proposedmodels fall into three general categories, which are: coat-core, subunit (sub-micelles, and internal structure models. The coat-core models, proposed by Waugh and Nobel in 1965, Payens in 1966, Parry and Carroll in 1969, and Paquin and co-workers in 1987, describe the micelle as an aggregate of caseins with outer layer differing in composition form the interior, and the structure of the inner part is not accurately identified. The sub-micelle models, proposed by Morr in 1967, Slattery and Evard in 1973, Schmidt in 1980, Walstra in1984, and Ono and Obata in 1989, is considered to be composed of roughly spherical uniform subunits. The last models, the internal structure models, which were proposed by Rose in 1969, Garnier and Ribadeau- Dumas in 1970, Holt in 1992, and Horne in 1998, specify the mode of aggregation of the different caseins.

  12. Structural properties of self-assembled polymeric micelles

    Mortensen, K.


    At present, the thermodynamic understanding of complex copolymer systems is undergoing important developments. Block copolymers aggregate in selective solvents into micelles of various form and size depending on molecular architecture and interaction parameters. The micelles constitute the basis...... for a variety of novel mesophases, including biocontinuous phases and networks of ordered cross-linking micelles. Research has focused on structural studies of block copolymer systems, using small-angle scattering of X-rays and neutrons....

  13. Aggregation operators on intuitionistic trapezoidal fuzzy number and its application to multi-criteria decision making problems

    Wang Jianqiang; Zhang Zhong


    Intuitionistic trapezoidal fuzzy numbers and their operational laws are defined. Based on these op-erational laws, some aggregation operators, including intuitionistic trapezoidal fuzzy weighted arithmetic averaging operator and weighted geometric averaging operator are proposed. Expected values, score function, and accuracy function of intuitionitsic trapezoidal fuzzy numbers are defined. Based on these, a kind of intuitionistic trapezoidal fuzzy multi-criteria decision making method is proposed. By using these aggregation operators, criteria values are aggregated and integrated intuitionistic trapezoidal fuzzy numbers of alternatives are attained. By comparing score function and accuracy function values of integrated fuzzy numbers, a ranking of the whole alternative set can be attained. An example is given to show the feasibility and availability of the method.

  14. Aggregation Operators on Triangular Intuitionistic Fuzzy Numbers and its Application to Multi-Criteria Decision Making Problems

    Liang Changyong


    Full Text Available The aim of this work is to present some aggregation operators with triangular intuitionistic fuzzy numbers and study their desirable properties. Firstly, the score function and the accuracy function of triangular intuitionistic fuzzy number are given, the method for ranking triangular intuitionistic fuzzy numbers are developed. Then, some geometric aggregation operators for aggregating triangular intuitionistic fuzzy numbers are developed, such as triangular intuitionistic fuzzy weighted geometric (TIFWG operator, the triangular intuitionistic fuzzy ordered weighted geometric (TIFOWG operator and the triangular intuitionistic fuzzy hybrid geometric (TIFHG operator. Moreover, an application of the new approach to multi-criteria decision making method was proposed based on the geometric average operator of TIFNs, and the new ranking method for TIFNs is used to rank the alternatives. Finally, an example analysis is given to verify and demonstrate the practicality and effectiveness of the proposed method.

  15. Time-resolved fluorescence quenching studies of sodium lauryl ether sulfate micelles

    Friedrich, Leidi C.; Silva, Volnir O.; Quina, Frank H., E-mail: [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Quimica; Moreira Junior, Paulo F. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Escola Politecnica. Departamento de Engenharia Quimica; Tcacenco, Celize M. [Fundacao Instituto de Ensino para Osasco (FIEO/UNIFIEO), SP (Brazil). Centro Universitario FIEO. Centro de Estudos Quimicos


    Aggregation numbers (N{sub Ag}) of micelles of the commercial anionic detergent sodium lauryl ether sulfate (SLES), with an average of two ethylene oxide subunits, were determined at 30 and 40 deg C by the time-resolved fluorescence quenching method with pyrene as the fluorescent probe and the N-hexadecylpyridinium ion as the quencher. The added-salt dependent growth of SLES micelles ({gamma} = 0.11-0.15, where {gamma} is the slope of a plot of log aggregation number vs. log [Y{sub aq}] and [Y{sub aq}] is the sodium counterion concentration free in the intermicellar aqueous phase) is found to be significantly lower than that of sodium alkyl sulfate micelles ({gamma} ca. 0.25), a difference attributed to the larger headgroup size of SLES. The I{sub 1}/I{sub 3} vibronic intensity ratio and the rate constant for intramicellar quenching of pyrene show that the pyrene solubilization microenvironment and the intramicellar microviscosity are insensitive to micelle size or the presence of added salt. (author)

  16. Time-resolved fluorescence quenching studies of sodium lauryl ether sulfate micelles

    Friedrich, Leidi C.; Silva, Volnir O.; Quina, Frank H., E-mail: [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Instituto de Quimica; Moreira Junior, Paulo F. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil). Escola Politecnica. Departamento de Engenharia Quimica; Tcacenco, Celize M. [Fundacao Instituto de Ensino para Osasco (FIEO/UNIFIEO), SP (Brazil). Centro Universitario FIEO. Centro de Estudos Quimicos


    Aggregation numbers (N{sub Ag}) of micelles of the commercial anionic detergent sodium lauryl ether sulfate (SLES), with an average of two ethylene oxide subunits, were determined at 30 and 40 deg C by the time-resolved fluorescence quenching method with pyrene as the fluorescent probe and the N-hexadecylpyridinium ion as the quencher. The added-salt dependent growth of SLES micelles ({gamma} = 0.11-0.15, where {gamma} is the slope of a plot of log aggregation number vs. log [Y{sub aq}] and [Y{sub aq}] is the sodium counterion concentration free in the intermicellar aqueous phase) is found to be significantly lower than that of sodium alkyl sulfate micelles ({gamma} ca. 0.25), a difference attributed to the larger headgroup size of SLES. The I{sub 1}/I{sub 3} vibronic intensity ratio and the rate constant for intramicellar quenching of pyrene show that the pyrene solubilization microenvironment and the intramicellar microviscosity are insensitive to micelle size or the presence of added salt. (author)

  17. Small-angle neutron scattering study of sodium cholate and sodium deoxycholate interacting micelles in aqueous medium

    J Santhanalakshmi; G Shantha Lakshmi; V K Aswal; P S Goyal


    Small angle neutron scattering (SANS) measurements of D2O solutions (0 1 M) of sodium cholate (NaC) and sodium deoxycholate (NaDC) were carried out at = 298 K. Under compositions very much above the critical micelle concentration (CMC), the bile salt micelle size growths were monitored by adopting Hayter-Penfold type analysis of the scattering data. NaC and NaDC solutions show presence of correlation peaks at = 0 12 and 0 1 Å-1 respectively. Monodisperse ellipsoids of the micelles produce best fits. For NaC and NaDC systems, aggregation number (9 0, 16 0), fraction of the free counterions per micelle (0 79, 0 62), semi-minor (8 0 Å) and semi-major axes (18 4, 31 7 Å) values for the micelles were deduced. Extent of micellar growth was studied using ESR correlation time measurements on a suitable probe incorporating NaC and NaDC micelles. The growth parameter (axial ratio) values were found to be 2 3 and 4 0 for NaC and NaDC systems respectively. The values agree with those of SANS.

  18. Dependence of micelle size and shape on detergent alkyl chain length and head group.

    Ryan C Oliver

    Full Text Available Micelle-forming detergents provide an amphipathic environment that can mimic lipid bilayers and are important tools for solubilizing membrane proteins for functional and structural investigations in vitro. However, the formation of a soluble protein-detergent complex (PDC currently relies on empirical screening of detergents, and a stable and functional PDC is often not obtained. To provide a foundation for systematic comparisons between the properties of the detergent micelle and the resulting PDC, a comprehensive set of detergents commonly used for membrane protein studies are systematically investigated. Using small-angle X-ray scattering (SAXS, micelle shapes and sizes are determined for phosphocholines with 10, 12, and 14 alkyl carbons, glucosides with 8, 9, and 10 alkyl carbons, maltosides with 8, 10, and 12 alkyl carbons, and lysophosphatidyl glycerols with 14 and 16 alkyl carbons. The SAXS profiles are well described by two-component ellipsoid models, with an electron rich outer shell corresponding to the detergent head groups and a less electron dense hydrophobic core composed of the alkyl chains. The minor axis of the elliptical micelle core from these models is constrained by the length of the alkyl chain, and increases by 1.2-1.5 Å per carbon addition to the alkyl chain. The major elliptical axis also increases with chain length; however, the ellipticity remains approximately constant for each detergent series. In addition, the aggregation number of these detergents increases by ∼16 monomers per micelle for each alkyl carbon added. The data provide a comprehensive view of the determinants of micelle shape and size and provide a baseline for correlating micelle properties with protein-detergent interactions.

  19. Generalized Einstein Aggregation Operators Based on the Interval Neutrosophic Numbers and Their Application to Multi-attribute Group Decision Making

    Don Hass


    Based on the Einstein operator, the operational rules of interval neutrosophic numbers are defined, according to the combination of Einstein operations and generalized aggregation operators, the interval neutrosophic generalized weighted Einstein average (INGWEA) operator, interval neutrosophic generalized ordered weighted Einstein average (INGOWEA) operator and interval neutrosophic generalized hybrid weighted Einstein average (INGHWEA) operator are proposed .

  20. Effect of nucleoside analogue antimetabolites on the structure of PEO–PPO–PEO micelles investigated by SANS

    Han, Youngkyu; Zhang, Zhe; Smith, Gregory S.; Do, Changwoo


    The effect of three nucleoside analogue antimetabolites (5-fluorouracil, floxuridine, and gemcitabine) on the structure of Pluronic L62 copolymer micelles was investigated using small-angle neutron scattering. These antimetabolites used for cancer chemotherapy have analogous molecular structures but different molecular sizes and aqueous solubilities. It was found that the addition of the three antimetabolites slightly reduced the micellar size and aggregation number, and the micellar anisotropy. The added antimetabolites also changed the internal molecular distribution of the micelles as measured by the scattering length densities, resulting in enhanced hydration of the hydrophobic core region of the micelle. The strength of the effect was found to correlate with the molecular properties of the model drugs, i.e. a larger molecular size and a higher aqueous solubility lead to enhanced hydration of the micellar core.

  1. Photophysical properties of pyronin dyes in reverse micelles of AOT

    Bayraktutan, Tuğba; Meral, Kadem; Onganer, Yavuz, E-mail:


    The photophysical properties of pyronin B (PyB) and pyronin Y (PyY) in reverse micelles formed with water/sodium bis (2-ethyl-1-hexyl) sulfosuccinate (AOT)/n-heptane were investigated by UV–vis absorption, steady-state and time-resolved fluorescence spectroscopy techniques. This study was carried out a wide range of reverse micelle sizes, with hydrodynamic radii ranging from 1.85 to 9.38 nm. Significant photophysical parameters as band shifts, fluorescence quantum yields and fluorescence lifetimes were determined to understand how photophysical and spectroscopic features of the dye compounds were affected by the variation of reverse micelle sizes. In this regard, control of reverse micelle size by changing W{sub 0}, the molar ratio of water to surfactant, allowed tuning the photophysical properties of the dyes in organic solvent via reverse micelle. Non-fluorescent H-aggregates of pyronin dyes were observed for the smaller reverse micelles whereas an increase in the reverse micelle size induced an increment in the amount of dye monomers instead of dye aggregates. Thus, the fluorescence intensities of the dyes were improved by increasing W{sub 0} due to the predomination of the fluorescent dye monomers. As a result, the fluorescence quantum yields also increased. The fluorescence lifetimes of the dyes in the reverse micelles were determined by the time-resolved fluorescence decay studies. Evaluation of the fluorescence lifetimes calculated for pyronin dyes in the reverse micelles showed that the size of reverse micelle affected the fluorescence lifetimes of pyronin dyes. -- Highlights: • The photophysical properties of pyronin dyes were examined by spectroscopic techniques. • Optical properties of the dyes were tuned by changing of W{sub 0} values. • The fluorescence lifetime and quantum yield values of the dyes in reverse micelles were discussed.

  2. Formation and Fluorimetric Characterization of Micelles in a Micro-flow Through System with Static Micro Mixer

    J. Michael Köhler


    Full Text Available The formation and behaviour of micelles of sodium dodecylsulfate in water byuse of a static micro mixer were studied. Trisbipyridylruthenium(II was applied asindicator dye, 9-methylanthracene was used for fluorescence quenching. All experimentswere carried out by a micro fluid arrangement with three syringe pumps, a 2 1 two-stepstatic micro mixer (IPHT Jena and a on-line micro fluorimetry including a luminescencediode for excitation, a blue glass filter (BG 7, Linos, two edge filters (RG 630, Linos anda photo counting module (MP 900, Perkin Elmer. It was possible to measure thefluorescence inside the PTFE tube (inner diameter 0.5 mm directly. A linear dependenceof fluorescence intensity from dye concentration was observed in absence of quencher andsurfactant as expected. An aggregation number of about 62 was found in the flow raterange between 300 and 800 μL/min. The fluorescence intensity increases slightly, butsignificant with increasing flow rate, if no quencher is present. In the presence of quencher,the fluorescence intensity decreases with decreasing surfactant concentration and withenhanced flow rate. The strength of the flow rate effect on the fluorescence increases withdecreasing surfactant concentration. The size of micelles was determined in micro channelsby the micro fluorimetric method in analogy to the conventional system. The micellesextract the quencher from the solution and lower, this way, the quenching effect. The sizeof micelles was estimated and it could be shown, that the flow rate has only low effect onthe aggregation number at the investigated flow rates. The effect of flow rate andsurfactant concentration on the fluorescence in the presence of quencher was interpreted asa shift in the micelle concentration due to the shear forces. It is expected, that thefluorescence intensity is lowered, if more quencher molecules are molecular disperse distributed inside the solution. Obviously, the lowered fluorescence

  3. Structure of Poly(styrene-b-ethylene-alt-propylene) Diblock Copolymer Micelles in Squalane

    Choi, Soo-Hyung; Bates, Frank S.; Lodge, Timothy P.; (UMM)


    The temperature dependence of the micellar structures formed by poly(styrene-b-ethylene-alt-propylene) (SEP) diblock copolymers in squalane, a highly selective solvent for the PEP blocks, has been studied using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Four SEP diblock copolymers were prepared by sequential anionic polymerization of styrene and isoprene, followed by hydrogenation of the isoprene blocks, to yield SEP(17-73), SEP(26-66), SEP(36-69), and SEP(42-60), where the numbers indicate block molecular weights in kDa. All four polymers formed well-defined spherical micelles. In dilute solution, DLS provided the temperature-dependent mean hydrodynamic radius, R{sub h}, and its distribution, while detailed fitting of the SAXS profiles gave the core radius, R{sub c}, the equivalent hard sphere radius, R{sub hs}, and an estimate of the aggregation number, N{sub agg}. In general, the micelles became smaller as the critical micelle temperature (CMT) was approached, which was well above the glass transition of the core block. As concentration increased the micelles packed onto body centered cubic lattices for all four copolymers, which underwent order-disorder transitions upon heating near the dilute solution CMTs. The results are discussed in terms of current understanding of block copolymer solution self-assembly, and particular attention is paid to the issue of equilibration, given the high glass transition temperature of the core block.

  4. Structure of poly(styrene-b-ethylene-alt-propylene) diblock copolymer micelles in squalane.

    Choi, Soo-Hyung; Bates, Frank S; Lodge, Timothy P


    The temperature dependence of the micellar structures formed by poly(styrene-b-ethylene-alt-propylene) (SEP) diblock copolymers in squalane, a highly selective solvent for the PEP blocks, has been studied using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS). Four SEP diblock copolymers were prepared by sequential anionic polymerization of styrene and isoprene, followed by hydrogenation of the isoprene blocks, to yield SEP(17-73), SEP(26-66), SEP(36-69), and SEP(42-60), where the numbers indicate block molecular weights in kDa. All four polymers formed well-defined spherical micelles. In dilute solution, DLS provided the temperature-dependent mean hydrodynamic radius, R(h), and its distribution, while detailed fitting of the SAXS profiles gave the core radius, R(c), the equivalent hard sphere radius, R(hs), and an estimate of the aggregation number, N(agg). In general, the micelles became smaller as the critical micelle temperature (CMT) was approached, which was well above the glass transition of the core block. As concentration increased the micelles packed onto body centered cubic lattices for all four copolymers, which underwent order-disorder transitions upon heating near the dilute solution CMTs. The results are discussed in terms of current understanding of block copolymer solution self-assembly, and particular attention is paid to the issue of equilibration, given the high glass transition temperature of the core block.

  5. Sucrose monoester micelles size determined by Fluorescence Correlation Spectroscopy (FCS.

    Susana A Sanchez

    Full Text Available One of the several uses of sucrose detergents, as well as other micelle forming detergents, is the solubilization of different membrane proteins. Accurate knowledge of the micelle properties, including size and shape, are needed to optimize the surfactant conditions for protein purification and membrane characterization. We synthesized sucrose esters having different numbers of methylene subunits on the substituent to correlate the number of methylene groups with the size of the corresponding micelles. We used Fluorescence Correlation Spectroscopy (FCS and two photon excitation to determine the translational D of the micelles and calculate their corresponding hydrodynamic radius, R(h. As a fluorescent probe we used LAURDAN (6-dodecanoyl-2-dimethylaminonaphthalene, a dye highly fluorescent when integrated in the micelle and non-fluorescent in aqueous media. We found a linear correlation between the size of the tail and the hydrodynamic radius of the micelle for the series of detergents measured.

  6. Characterization of phospholipid mixed micelles by translational diffusion.

    Chou, James J; Baber, James L; Bax, Ad


    The concentration dependence of the translational self diffusion rate, D (s), has been measured for a range of micelle and mixed micelle systems. Use of bipolar gradient pulse pairs in the longitudinal eddy current delay experiment minimizes NOE attenuation and is found critical for optimizing sensitivity of the translational diffusion measurement of macromolecules and aggregates. For low volume fractions Phi (Phi\\\\ le 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D (s)= D (o)(1-3.2lambdaPhi) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D (s) at infinitely dilute concentration, is found to be about 2.6 times the unhydrated molecular volume. Using the data collected for hen egg white lysozyme as a reference, diffusion data for dihexanoyl phosphatidylcholine (DHPC) micelles indicate approximately 27 molecules per micelle, and a critical micelle concentration of 14 mM. Differences in translational diffusion rates for detergent and long chain phospholipids in mixed micelles are attributed to rapid exchange between free and micelle-bound detergent. This difference permits determination of the free detergent concentration, which, for a high detergent to long chain phospholipid molar ratio, is found to depend strongly on this ratio. The hydrodynamic volume of DHPC/POPC bicelles, loaded with an M2 channel peptide homolog, derived from translational diffusion, predicts a rotational correlation time that slightly exceeds the value obtained from peptide (15)N relaxation data.

  7. Characterization of Phospholipid Mixed Micelles by Translational Diffusion

    Chou, James J. [Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology (United States); Baber, James L.; Bax, Ad [National Institutes of Health, Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases (United States)], E-mail:


    The concentration dependence of the translational self diffusion rate, D{sub s}, has been measured for a range of micelle and mixed micelle systems. Use of bipolar gradient pulse pairs in the longitudinal eddy current delay experiment minimizes NOE attenuation and is found critical for optimizing sensitivity of the translational diffusion measurement of macromolecules and aggregates. For low volume fractions {phi} ({phi} {<=} 15% v/v) of the micelles, experimental measurement of the concentration dependence, combined with use of the D{sub s}=D{sub o}(1-3.2{lambda}{phi}) relationship, yields the hydrodynamic volume. For proteins, the hydrodynamic volume, derived from D{sub s} at infinitely dilute concentration, is found to be about 2.6 times the unhydrated molecular volume. Using the data collected for hen egg white lysozyme as a reference, diffusion data for dihexanoyl phosphatidylcholine (DHPC) micelles indicate approximately 27 molecules per micelle, and a critical micelle concentration of 14 mM. Differences in translational diffusion rates for detergent and long chain phospholipids in mixed micelles are attributed to rapid exchange between free and micelle-bound detergent. This difference permits determination of the free detergent concentration, which, for a high detergent to long chain phospholipid molar ratio, is found to depend strongly on this ratio. The hydrodynamic volume of DHPC/POPC bicelles, loaded with an M2 channel peptide homolog, derived from translational diffusion, predicts a rotational correlation time that slightly exceeds the value obtained from peptide {sup 15}N relaxation data.

  8. Chirality-mediated polypeptide micelles for regulated drug delivery.

    Ding, Jianxun; Li, Chen; Zhang, Ying; Xu, Weiguo; Wang, Jincheng; Chen, Xuesi


    Two kinds of triblock poly(ethylene glycol)-polyleucine (PEG-PLeu) copolymers were synthesized through the ring-opening polymerization of L-Leu N-carboxyanhydride (NCA), or equivalent D-Leu NCA and L-Leu NCA with amino-terminated PEG as a macroinitiator. The amphiphilic copolymers spontaneously self-assembled into spherical micellar aggregations in an aqueous environment. The micelle with a racemic polypeptide core exhibited smaller critical micelle concentration and diameter compared to those with a levorotatory polypeptide core. A model anthracycline antineoplastic agent, i.e., doxorubicin (DOX), was loaded into micelles through nanoprecipitation, and the PEG-P(D,L-Leu) micelle exhibited higher drug-loading efficacy than that with a P(L-Leu) core-this difference was attributed to the flexible and compact P(L-Leu) core. Sustained in vitro DOX release from micelles with both levorotatory and racemic polypeptide cores was observed, and the DOX-loaded PEG-P(D,L-Leu) micelle exhibited a slower release rate. More interestingly, DOX-loaded micelles exhibited chirality-mediated antitumor efficacy in vitro and in vivo, which are all better than that of free DOX. Furthermore, both enhanced tumor inhibition and excellent security in vivo were confirmed by histopathological or in situ cell apoptosis analyses. Therefore, DOX-loaded PEG-PLeu micelles appear to be an interesting nanoscale polymeric formulation for promising malignancy chemotherapy.

  9. Structure and dynamics of cholic acid and dodecylphosphocholine-cholic acid aggregates.

    Sayyed-Ahmad, Abdallah; Lichtenberger, Lenard M; Gorfe, Alemayehu A


    Bile acids are powerful detergents that emulsify and solubilize lipids, vitamins, cholesterol and other molecules in the biliary tract and intestines. It has long been known that bile acids form soluble mixed micelles with lipids. However, the detailed thermodynamic and structural properties of these micelles are not fully understood. This study sheds light on this issue based on results from multiple molecular dynamics simulations of cholic acid (CA) and dodecylphosphocholine (DPC) mixed micelles. We found that CA molecules form aggregates of up to 12 monomers with a mean size of 5-6. In agreement with several previous simulations and earlier predictions, the overall shape of these CA clusters is oblate disk-like such that the methyl groups point toward the core of the aggregate and the hydroxyl groups point away from it. The self-aggregation behavior of the CA clusters in the DPC-CA mixture is similar to the pure CA. Furthermore, the sizes and aggregation numbers of the DPC-CA mixed micelles are linearly dependent on CA molarity. In agreement with the radial shell model of Nichols and Ozarowski [Nichols, J. W.; Ozarowski, J. Biochemistry 1990, 29, 4600], our results demonstrate that CA molecules form a wedge between the DPC molecules with their hydroxyl and carboxyl groups facing the aqueous phase while their methyl groups are buried in and face the hydrocarbon core of the DPC micelle. The DPC-CA micelles simulated here tend to be spherical to prolate in shape, with the deviation from spherical geometry significantly increasing with increasing CA:DPC ratio.

  10. Micellar copolymerization of associative polymers: study of the effect of acrylamide on sodium dodecyl sulfate-poly(propylene oxide) methacrylate mixed micelles.

    Bastiat, Guillaume; Grassl, Bruno; François, Jeanne


    Mixed micelles of sodium dodecyl sulfate (SDS) and poly(propylene oxide) methacrylate (PPOMA) have been studied in the presence of acrylamide using conductimetry, fluorescence spectroscopy, and small-angle neutron scattering (SANS) under the following conditions: (i) the SDS-acrylamide binary system in water; (ii) the SDS-acrylamide-PPOMA ternary system in water. The addition of acrylamide in SDS solutions perturbs the micellization of the surfactant by decreasing the aggregation number of the micelles and increasing their ionization degree. The variations of the various micellar parameters versus the weight ratio R=PPOMA/SDS are different in the presence of acrylamide or in pure water. These differences are much more pronounced for the lower than for the higher PPOMA concentrations. There is competition between acrylamide and PPOMA and at higher PPOMA concentration, acrylamide tends to be released from SDS micelles and is completely replaced by PPOMA.

  11. Complex coacervate core micelles.

    Voets, Ilja K; de Keizer, Arie; Cohen Stuart, Martien A


    In this review we present an overview of the literature on the co-assembly of neutral-ionic block, graft, and random copolymers with oppositely charged species in aqueous solution. Oppositely charged species include synthetic (co)polymers of various architectures, biopolymers - such as proteins, enzymes and DNA - multivalent ions, metallic nanoparticles, low molecular weight surfactants, polyelectrolyte block copolymer micelles, metallo-supramolecular polymers, equilibrium polymers, etcetera. The resultant structures are termed complex coacervate core/polyion complex/block ionomer complex/interpolyelectrolyte complex micelles (or vesicles); i.e., in short C3Ms (or C3Vs) and PIC, BIC or IPEC micelles (and vesicles). Formation, structure, dynamics, properties, and function will be discussed. We focus on experimental work; theory and modelling will not be discussed. Recent developments in applications and micelles with heterogeneous coronas are emphasized.

  12. The Aggregate behavior of branch points--measuring the number and velocity of atmospheric turbulence layers.

    Oesch, Denis W; Sanchez, Darryl J; Matson, Charles L


    Optical waves propagating through atmospheric turbulence develop spatial and temporal variations in their phase. For sufficiently strong turbulence, these phase differences can lead to interference in the propagating wave and the formation of branch points; positions of zero amplitude. Under the assumption of a layered turbulence model, we show that these branch points can be used to estimate the number and velocities of atmospheric layers. We describe how to carry out this estimation process and demonstrate its robustness in the presence of sensor noise.

  13. Micelles in mixtures of sodium dodecyl sulfate and a bolaform surfactant.

    Muzzalupo, Rita; Gente, Giacomo; La Mesa, Camillo; Caponetti, Eugenio; Chillura-Martino, Delia; Pedone, Lucia; Saladino, Maria Luisa


    Mixtures composed of water, sodium dodecyl sulfate (SDS), and a bolaform surfactant with two aza-crown ethers as polar headgroups (termed Bola C-16) were investigated by modulating the mole ratios between the components. The two surfactants have ionic and nonionic, but ionizable, headgroups, respectively. The ionization is due to the complexation of alkali ions by the aza-crown ether unit(s). Structural, thermodynamic, and transport properties of the above mixtures were investigated. Results from surface tension, translational self-diffusion, and small angle neutron scattering (SANS) are reported and discussed. Interactions between the two surfactants to form mixed micelles result in a combination of electrostatic and hydrophobic contributions. These effects are reflected in the size and shape of the aggregates as well as in transport properties. The translational diffusion of the components in mixed micelles, in particular, depends on the Bola C-16/SDS mole ratio. Nonideality of mixing of the two components was inferred from the dependence of the critical micelle concentration, cmc, on the mole fraction of Bola C-16. This behavior is also reflected in surface adsorption and in the area per polar headgroup at the air-water interface. SANS data analysis for the pure components gives results in good agreement with previous findings. An analysis of data relative to mixed systems allows us to compute some structural parameters of the mixed aggregates. The dependence of aggregation numbers, nu(T), on the Bola C-16/SDS mole ratio displays a maximum that depends on the overall surfactant content and is rationalized in terms of the nonideality of mixing. Aggregates grow perpendicularly to the major rotation axis, as formerly observed in the Bola C-16 system, and become progressively ellipsoidal in shape.

  14. Chain exchange in block copolymer micelles

    Lu, Jie; Bates, Frank; Lodge, Timothy


    Block copolymer micelles are aggregates formed by self-assembly of amphiphilic copolymers dispersed in a selective solvent, driven by unfavorable interactions between the solvent and the core-forming block. Due to the relatively long chains being subject to additional thermodynamic and dynamic constraints (e.g., entanglements, crystallinity, vitrification), block copolymer micelles exhibit significantly slower equilibration kinetics than small molecule surfactants. As a result, details of the mechanism(s) of equilibration in block copolymer micelles remain unclear. This present works focuses on the chain exchange kinetics of poly(styrene-b-ethylenepropylene) block copolymers in squalane (C30H62) using time-resolved small angle neutron scattering (TR-SANS). A mixture of h-squalane and d-squalane is chosen so that it contrast matches a mixed 50/50 h/d polystyrene micelle core. When the temperature is appropriate and isotopically labeled chains undergo mixing, the mean core contrast with respect to the solvent decreases, and the scattering intensity is therefore reduced. This strategy allows direct probing of chain exchange rate from the time dependent scattering intensity I(q, t).

  15. Small angle neutron scattering study of mixed micelles of oppositely charged surfactants

    J V Joshi; V K Aswal; P S Goyal


    Structures of mixed micelles of oppositely charged surfactants dodecyltrimethylammonium bromide (DTAB) and sodium dodecyl sulphate (SDS) have been studied using small angle neutron scattering. The concentration of one of the components was kept fixed (0.3 M) and that of another varied in the range 0 to 0.1 M. The aggregation number and micellar size increase and fractional charge decreases dramatically with the addition of small amount of oppositely charged surfactant. The effect of addition of SDS on DTAB is significantly different from that of the addition of DTAB on SDS. The contrast variation SANS experiments using deuterated surfactant suggests the homogeneous mixing of two components in mixed micellar system.

  16. Aggregation in Organic Solutions of Malonamides: Consequences for Water Extraction

    Meridiano, Y.; Berthon, L.; Crozes, X.; Sorel, C. [CEA ValRho, DEN DRCP SCPS LCSE, F-30207 Bagnols Sur Ceze, (France); Dannus, P. [CEA Saclay, INSTN UEIN, F-91191 Gif Sur Yvette, (France); Antonio, M.R.; Chiarizia, R. [Argonne Natl Lab, CSE Div, Argonne, IL 60439 (United States); Zemb, T. [CEA CNRS UM2 ENSCM, Inst Chin Separat Marcoule, Bagnols Sur Ceze, (France)


    The molecular organization of N, N'-dimethyl-N, N'-dioctyl-hexyl-ethoxy-malonamide (DMDOHEMA), the current reference extractant for the DIAMEX (Diamide Extraction) process, is correlated with its water extraction properties from neutral media. The aggregation of DMDOHEMA in n-heptane was investigated by vapor pressure osmometry (VPO) and the aggregate speciation characterized by combined small-angle neutron and X-ray scattering (SANS and SAXS, respectively). Two approaches were taken to model the aggregation of the diamide and the water extraction as a function of the diamide concentration by taking into account a single aggregation equilibrium with an average aggregation number N equal to 4.28 {+-} 0.05; and a competition between two types of aggregates in the organic phase, namely, aggregates of the reverse micelle type with 4 diamides per aggregate, and an oligomeric structure composed of about 10 diamide molecules which appears at high extractant concentration ({>=} 1 mol/L). In both cases, the supramolecular speciation representing the monomers/aggregates distribution was determined, and for each supramolecular organization, a solubilization parameter was calculated using the Sergievskii-Dannus relationship. Thus, the correlation between the two types of micellization of the diamide and the extraction of water into the organic phase was demonstrated. The larger aggregates can extract about five times more water than monomers. (authors)

  17. Fluorosurfactants at structural extremes: adsorption and aggregation.

    Eastoe, Julian; Rogers, Sarah E; Martin, Laura J; Paul, Alison; Guittard, Frédéric; Guittard, Elisabeth; Heenan, Richard K; Webster, John R P


    Fluorosurfactants with several structural modifications have been synthesized, and the air/water interface and bulk aggregation properties investigated. The compounds were fluorinated ethylene oxide (EO) nonionics where the number and position of the hydrophilic group(s) has been radically altered to generate linear, bolaform, and Y-shaped analogues. A noticeable structure-interfacial packing relationship was observed via both tensiometric measurements and neutron reflection studies: the limiting molecular areas, a(cmc), and surface excesses, gamma(cmc), are strongly dependent on the number and position of the EO headgroups. Differing bulk aqueous properties were also observed. Small-angle neutron scattering shows an evolution of micelle structure from cylindrical to disk-like aggregates on changing from Y-shaped to bolaform molecular structure.

  18. Integral physicochemical properties of reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT)

    Fedyaeva, O. A.; Shubenkova, E. G.; Poshelyuzhnaya, E. G.; Lutaeva, I. A.


    The effect the degree of hydration has on optical and electrophysical properties of water/AOT/ n-hexane system is studied. It is found that AOT reverse micelles form aggregates whose dimensions grow along with the degree of hydration and temperature. Aggregation enhances their electrical conductivity and shifts the UV spectrum of AOT reverse emulsions to the red region. Four states of water are found in the structure of AOT reverse micelles.

  19. Smart wormlike micelles design, characteristics and applications

    Feng, Yujun; Dreiss, Cécile A


    This Brief provides an up-to-date overview of smart surfactants and describes a broad spectrum of triggers that induce the formation of wormlike micelles or reversibly tune the morphology of surfactant aggregates from wormlike micelles to another state, or vice versa. Combining the fields of chemistry, physics, polymer science, and nanotechnology, its primary focus is on the design, formulation, and processing of intelligent viscoelastic surfactant solutions, covering the scientific principles governing responsiveness to one or more particular triggers, down to the end-use-driven functions. The first chapter explains why and how surfactants self-assemble into viscoelastic wormlike micellar solutions reminiscent of polymer solutions, while the following chapters show how the response to a given trigger translates into macroscopic rheological changes, including temperature, light, pH, CO2, redox, hydrocarbon, etc. The last chapter demonstrates the applications of these viscoelastic assemblies in oil and gas pro...

  20. Revealing and tuning the core, structure, properties and function of polymer micelles with lanthanide-coordination complexes.

    Wang, Junyou; Groeneveld, Andrea; Oikonomou, Maria; Prusova, Alena; Van As, Henk; van Lent, Jan W M; Velders, Aldrik H


    Controlling self-assembly processes is of great interest in various fields where multifunctional and tunable materials are designed. We here present the versatility of lanthanide-complex-based micelles (Ln-C3Ms) with tunable coordination structures and corresponding functions (e.g. luminescence and magnetic relaxation enhancement). Micelles are prepared by charge-driven self-assembly of a polycationic-neutral diblock copolymer and anionic coordination complexes formed by Ln(III) ions and the bis-ligand L2EO4, which contains two dipicolinic acid (DPA) ligand groups (L) connected by a tetra-ethylene oxide spacer (EO4). By varying the DPA/Ln ratio, micelles are obtained with similar size but with different stability, different aggregation numbers and different oligomeric and polymeric lanthanide(III) coordination structures in the core. Electron microscopy, light scattering, luminescence spectroscopy and magnetic resonance relaxation experiments provide an unprecedented detailed insight into the core structures of such micelles. Concomitantly, the self-assembly is controlled such that tunable luminescence or magnetic relaxation with Eu-C3Ms, respectively, Gd-C3Ms is achieved, showing potential for applications, e.g. as contrast agents in (pre)clinical imaging. Considering the various lanthanide(III) ions have unique electron configurations with specific physical chemical properties, yet very similar coordination chemistry, the generality of the current coordination-structure based micellar design shows great promise for development of new materials such as, e.g., hypermodal agents.

  1. Structure and flexibility of worm-like micelles

    Jerke, G.; Pedersen, J.S.; Egelhaaf, S.U.


    Small-angle neutron scattering and static light scattering experiments have been performed on worm-like micelles formed by soybean lecithin and trace amounts of water in deuterated iso-octane. The structure and flexibility of the aggregates have been investigated as a function of solution...

  2. Precipitate-Coacervate Transformation in Polyelectrolyte-Mixed Micelle Systems.

    Comert, Fatih; Nguyen, Duy; Rushanan, Marguerite; Milas, Peker; Xu, Amy Y; Dubin, Paul L


    The polycation/anionic-nonionic mixed micelle, poly(diallyldimethylammonium chloride)-sodium dodecyl sulfate/Triton X-100 (PDADMAC-SDS/TX100), is a model polyelectrolyte-colloid system in that the micellar mole fraction of SDS (Y) controls the micelle surface charge density, thus modulating the polyelectrolyte-colloid interaction. The exquisite temperature dependence of this system provides an important additional variable, controlling both liquid-liquid (L-L) and liquid-solid (L-S) phase separation, both of which are driven by the entropy of small ion release. In order to elucidate these transitions, we applied high-precision turbidimetry (±0.1 %), isothermal titration calorimetry, and epifluorescence microscopy which demonstrates preservation of micelle structure under all conditions. The L-S region at large Y including precipitation displays a remarkable linear, inverse Y-dependence of the L-S transition temperature Ts. In sharp contrast, the critical temperature for L-L coacervation Tφ, shows nearly symmetrical effects of positive and negative deviations in Y from the point of soluble complex neutrality, which is controlled in solution by the micelle charge and the number of micelles bound per polymer chain n (Zcomplex = Zpolymer + nZmicelle). In solid-like states, n no longer signifies the number of micelles bound per polymer chain, since the proximity of micelles inverts the host-guest relationship with each micelle binding multiple PE chains. This intimate binding goes hand-in-hand with the entropy of release of micelle-localized charge-compensating ions whose concentration depends on Y. These ions need not be released in L-L coacervation, but during L-S transition their displacement by PE accounts for the inverse dependence of Ts on micelle charge, Y.

  3. Dependence of aggregation behavior on concentration in triblock copolymer solutions: The effect of chain architecture

    Han, Xiang-Gang, E-mail:; Zhang, Xue-Feng [Key Laboratory of Integrated Exploitation of Bayan Obo Multi-Metal Resources School of Mathematics, Physics and Biological Engineering, Inner Mongolia University of Science and Technology, Baotou 014010 (China)


    Using the self-consistent field lattice technique, the effects of concentration and hydrophobic middle block length (where the chain length remains constant) on aggregation behavior are studied in amphiphilic symmetric triblock copolymer solutions. The heat capacity peak for the unimer-micelle transition and the distribution peaks for the different degrees of aggregation for micelles and small aggregates (submicelles) are calculated. Analysis of the conducted computer simulations shows that the transition broadness dependence on concentration is determined by the hydrophobic middle block length, and this dependence is distinctly different when the length of the hydrophobic middle block changes. Different size for small aggregates simultaneously appear in the transition region. As temperature decreases, the number of different size small aggregates for the large hydrophobic middle block length first ascends and then descends in aggregation degree order. These results indicate that any transition broadness change with concentration is related to the mechanism of fragmentation and fusion. These results are helpful for interpreting the aggregation process of amphiphilic copolymers at equilibrium.

  4. Aggregation of estimated numbers of undiscovered deposits: an R-script with an example from the Chu Sarysu Basin, Kazakhtan: Chapter B in Global mineral resource assessment

    Schuenemeyer, John H.; Zientek, Michael L.; Box, Stephen E.


    Mineral resource assessments completed by the U.S. Geological Survey during the past three decades express geologically based estimates of numbers of undiscovered mineral deposits as probability distributions. Numbers of undiscovered deposits of a given type are estimated in geologically defined regions. Using Monte Carlo simulations, these undiscovered deposit estimates are combined with tonnage and grade models to derive a probability distribution describing amounts of commodities and rock that could be present in undiscovered deposits within a study area. In some situations, it is desirable to aggregate the assessment results from several study areas. This report provides a script developed in open-source statistical software, R, that aggregates undiscovered deposit estimates of a given type, assuming independence, total dependence, or some degree of correlation among aggregated areas, given a user-specified correlation matrix.

  5. A neutron scattering study of triblock copolymer micelles

    Gerstenberg, M.C.


    The thesis describes the neutron scattering experiments performed on poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) triblock copolymer micelles in aqueous solution. The studies concern the non-ionic triblock copolymer P85 which consists of two outer segments of 25 monomers of ethylene oxide attached to a central part of 40 monomers of propylene oxide. The amphiphilic character of P85 leads to formation of various structures in aqueous solution such as spherical micelles, rod-like structures, and a BCC liquid-crystal mesophase of spherical micelles. The present investigations are centered around the micellar structures. In the first part of this thesis a model for the micelle is developed for which an analytical scattering form factor can be calculated. The micelle is modeled as a solid sphere with tethered Gaussian chains. Good agreement was found between small-angle neutron scattering experiments and the form factor of the spherical P85 micelles. Above 60 deg. C some discrepancies were found between the model and the data which is possibly due to an elongation of the micelles. The second part focuses on the surface-induced ordering of the various micellar aggregates in the P85 concentration-temperature phase diagram. In the spherical micellar phase, neutron reflection measurements indicated a micellar ordering at the hydrophilic surface of quartz. Extensive modeling was performed based on a hard sphere description of the micellar interaction. By convolution of the distribution of hard spheres at a hard wall, obtained from Monte Carlo simulations, and the projected scattering length density of the micelle, a numerical expression was obtained which made it possible to fit the data. The hard-sphere-hard-wall model gave an excellent agreement in the bulk micellar phase. However, for higher concentrations (25 wt % P85) close to the transition from the micellar liquid into a micellar cubic phase, a discrepancy was found between the model and the

  6. Evolution of mixed surfactant aggregates in solutions and at solid/solution interfaces

    Zhang, Rui

    Surfactant systems have been widely used in such as enhanced oil recovery, waste treatment and metallurgy, etc., in order to solve the problem of global energy crisis, to remove the pollutants and to generate novel energy resources. Almost all surfactant systems are invariably mixtures due to beneficial and economic considerations. The sizes and shapes of aggregates in solutions and at solid/solution interfaces become important, since the nanostructures of mixed aggregates determine solution and adsorption properties. A major hurdle in science is the lack of information on the type of complexes and aggregates formed by mixtures and the lack of techniques for deriving such information. Using techniques such as analytical ultracentrifuge, small angle neutron scattering, surface tension, fluorescence, cryo-TEM, light scattering and ultrafiltration, the nanostructures of aggregates of sugar based n-dodecyl-beta-D-maltoside (DM) and nonionic pentaethyleneglycol monododecyl ether or nonyl phenol ethoxylated decyl ether (NP-10) and their mixtures have been investigated to prove the hypothesis that the aggregation behavior is linked to packing of the surfactant governed by the molecular interactions as well as the molecular structures. The results from both sedimentation velocity and sedimentation equilibrium experiments suggest coexistence of two types of micelles in nonyl phenol ethoxylated decyl ether solutions and its mixtures with n-dodecyl-beta-D-maltoside while only one micellar species is present in n-dodecyl-beta-D-maltoside solutions, in good agreement with those from small angle neutron scattering, cryo-TEM, light scattering and ultrafiltration. Type I micelles were primary micelles at cmc while type II micelles were elongated micelles. On the other hand, the nanostructures of mixed surface aggregates have been quantitatively predicted for the first time using a modified packing index. As a continuation of the Somasundaran-Fuersteneau adsorption model, a

  7. Near-Infrared Squaraine Dye Encapsulated Micelles for in Vivo Fluorescence and Photoacoustic Bimodal Imaging.

    Sreejith, Sivaramapanicker; Joseph, James; Lin, Manjing; Menon, Nishanth Venugopal; Borah, Parijat; Ng, Hao Jun; Loong, Yun Xian; Kang, Yuejun; Yu, Sidney Wing-Kwong; Zhao, Yanli


    Combined near-infrared (NIR) fluorescence and photoacoustic imaging techniques present promising capabilities for noninvasive visualization of biological structures. Development of bimodal noninvasive optical imaging approaches by combining NIR fluorescence and photoacoustic tomography demands suitable NIR-active exogenous contrast agents. If the aggregation and photobleaching are prevented, squaraine dyes are ideal candidates for fluorescence and photoacoustic imaging. Herein, we report rational selection, preparation, and micelle encapsulation of an NIR-absorbing squaraine dye (D1) for in vivo fluorescence and photoacoustic bimodal imaging. D1 was encapsulated inside micelles constructed from a biocompatible nonionic surfactant (Pluoronic F-127) to obtain D1-encapsulated micelles (D1(micelle)) in aqueous conditions. The micelle encapsulation retains both the photophysical features and chemical stability of D1. D1(micelle) exhibits high photostability and low cytotoxicity in biological conditions. Unique properties of D1(micelle) in the NIR window of 800-900 nm enable the development of a squaraine-based exogenous contrast agent for fluorescence and photoacoustic bimodal imaging above 820 nm. In vivo imaging using D1(micelle), as demonstrated by fluorescence and photoacoustic tomography experiments in live mice, shows contrast-enhanced deep tissue imaging capability. The usage of D1(micelle) proven by preclinical experiments in rodents reveals its excellent applicability for NIR fluorescence and photoacoustic bimodal imaging.

  8. On the composition fluctuations of reverse micelles.

    Tovstun, Sergey A; Razumov, Vladimir F


    The polydispersity of the reverse micelles is determined mainly by the fluctuations of their composition. The composition of the reverse micelle is a two-dimensional random variable whose components are the numbers of water (i) and surfactant (j) molecules. In this study the fluctuations of the composition of the reverse micelles are considered in the Gaussian approximation. It is shown that the standard deviation of the quantity w=i/j may be calculated from the dependence of the water vapor pressure above the microemulsion on the molar ratio W=[water]/[surfactant]. The estimation based on the literature data for microemulsion system sodium bis(2-ethylhexyl)sulfosuccinate/water/isooctane at 37°C in the range W=0-18 has shown that the relative standard deviation of the quantity w is about 10%. It is shown that the value of the composition fluctuations is related to the dependence of average composition on the concentration of reverse micelles at constant parameter W.

  9. Molecular dynamics study of the potential of mean force of SDS aggregates

    Kawada, Shinji; Fujimoto, Kazushi; Yoshii, Noriyuki; Okazaki, Susumu


    In our previous study, all-atomistic molecular dynamics (MD) calculations have been carried out for the aggregation of ionic sodium dodecyl sulfate in water [S. Kawada et al., Chem. Phys. Lett. 646, 36 (2016)]. Aggregates of 20-30 dodecyl sulfate ions were formed within a short MD run for 10 ns. However, further aggregation did not occur despite a long MD calculation for more than 100 ns. This suggests that strong electrostatic repulsive interactions between the aggregates prevent the fusion of the aggregates. In the present study, mean force and potential of mean force acting between two aggregates with aggregation number N = 30 were evaluated as a function of their separation by MD calculations. The repulsive force becomes strong with decreasing distance between the two aggregates before they merge into one. An origin of the repulsive force is an electric double layer formed by the sulfate group and counter sodium ions. Strength of the repulsive force is in good agreement with the theoretical value given by the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Once the aggregates establish contact, the force between them turns to be a large attractive force that can be explained by the interfacial tension. In order to form a single micelle from the two aggregates, it is necessary for them to climb over a free energy barrier of 23 kJ/mol. Once, the barrier is overcome, the micelle is stabilized by ˜200 kJ/mol. The time constant of aggregation evaluated from the calculated free energy barrier was about 28 μs at the concentration in our previous study.

  10. Enzymatic reactions in reversed micelles

    Hilhorst, M.H.


    It has been recognised that enzymes in reversed micelles have potential for application in chemical synthesis. Before these expectations will be realised many problems must be overcome. This thesis deals with some of them.In Chapter 1 the present knowledge about reversed micelles and micellar enzymo

  11. Biochemical characterization of GM1 micelles-Amphotericin B interaction.

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M


    In this work a thorough characterization of the GM1 micelle-Amphotericin B (AmB) interaction was performed. The micelle formation as well as the drug loading occurs spontaneously, although influenced by the physicochemical conditions, pH and temperature. The chromatographic profile of GM1-AmB complexes at different molar ratios shows the existence of two populations. The differential absorbance of GM1, monomeric and aggregate AmB, allowed us to discriminate the presence of all of them in both fractions. Thus, we noted that at higher proportion of AmB in the complex, increases the larger population which is composed mainly of aggregated AmB. The physical behavior of these micelles shows that both GM1- AmB complexes were stable in solution for at least 30 days. However upon freeze-thawing or lyophilization-solubilization cycles, only the smallest population, enriched in monomeric AmB, showed a complete solubilization. In vitro, GM1-AmB micelles were significantly less toxic on cultured cells than other commercial micellar formulations as Fungizone, but had a similar behavior to liposomal formulations as Ambisome. Regarding the antifungal activity of the new formulation, it was very similar to that of other formulations. The characterization of these GM1-AmB complexes is discussed as a potential new formulation able to improve the antifungal therapeutic efficiency of AmB.

  12. Development, Characterization, and Evaluation of PSMA-Targeted Glycol Chitosan Micelles for Prostate Cancer Therapy

    Jing Xu


    Full Text Available Prostate cancer-binding peptides- (PCP- modified polymeric micelles were prepared and used for the treatment of prostate-specific membrane antigen- (PSMA- expressing prostate cancer in a target-specific manner. Cholesterol-modified glycol chitosan (CHGC was synthesized. PCP-conjugated CHGC (PCP-CHGC micelles were fabricated and characterized. The degree of substitution was 5.2 PCP groups and 5.8 cholesterol groups per 100 sugar residues of glycol chitosan. The critical aggregation concentration (CAC of PCP-CHGC copolymer was 0.0254 mg/mL. Doxorubicin (DOX was chosen as a model antitumor drug. The DOX-loaded micelles were prepared by an o/w method. The mean diameter of DOX-loaded PCP-CHGC (DOX-PCP-CHGC micelles was 293 nm determined by dynamic light scattering (DLS. DOX released from drug-loaded micelles was in a biphasic manner. DOX-PCP-CHGC micelles exhibited higher cytotoxicity in vitro against PSMA-expressing LNCaP cells than DOX-loaded CHGC (DOX-CHGC micelles. Moreover, the cellular uptake of DOX-PCP-CHGC micelles determined by confocal laser scanning microscopy (CLSM and flow cytometry was higher than that of DOX-CHGC micelles in LNCaP cells. Importantly, DOX-PCP-CHGC micelles demonstrated stronger antitumor efficacy against LNCaP tumor xenograft models than doxorubicin hydrochloride and DOX-CHGC micelles. Taken together, this study provides a potential way in developing PSMA-targeted drug delivery system for prostate cancer therapy.

  13. Characteristic of core materials in polymeric micelles effect on their micellar properties studied by experimental and dpd simulation methods.

    Cheng, Furong; Guan, Xuewa; Cao, Huan; Su, Ting; Cao, Jun; Chen, Yuanwei; Cai, Mengtan; He, Bin; Gu, Zhongwei; Luo, Xianglin


    Polymeric micelles are one important class of nanoparticles for anticancer drug delivery, but the impact of hydrophobic segments on drug encapsulation and release is unclear, which deters the rationalization of drug encapsulation into polymeric micelles. This paper focused on studying the correlation between the characteristics of hydrophobic segments and encapsulation of structurally different drugs (DOX and β-carotene). Poly(ϵ-caprolactone) (PCL) or poly(l-lactide) (PLLA) were used as hydrophobic segments to synthesize micelle-forming amphiphilic block copolymers with the hydrophilic methoxy-poly(ethylene glycol) (mPEG). Both blank and drug loaded micelles were spherical in shape with sizes lower than 50 nm. PCL-based micelles exhibited higher drug loading capacity than their PLLA-based counterparts. Higher encapsulation efficiency of β-carotene was achieved compared with DOX. In addition, both doxorubicin and β-carotene were released much faster from PCL-based polymeric micelles. Dissipative particle dynamics (DPD) simulation revealed that the two drugs tended to aggregate in the core of the PCL-based micelles but disperse in the core of PLLA based micelles. In vitro cytotoxicity investigation of DOX loaded micelles demonstrated that a faster drug release warranted a more efficient cancer-killing effect. This research could serve as a guideline for the rational design of polymeric micelles for drug delivery.

  14. Enhancement of bioavailability by formulating rhEPO ionic complex with lysine into PEG-PLA micelle

    Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu [Jilin University, College of Life Science (China); Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang, E-mail: [Yantai University, School of Pharmacy (China); Li, Youxin, E-mail: [Jilin University, College of Life Science (China)


    A composite micelle of ionic complex encapsulated into poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) di-block copolymeric micelles was used for protein drug delivery to improve its pharmacokinetic performance. In this study, recombinant human erythropoietin (rhEPO, as a model protein) was formulated with lysine into composite micelles at a diameter of 71.5 nm with narrow polydispersity indices (PDIs < 0.3). Only a trace amount of protein was in aggregate form. The zeta potential of the spherical micelles was ranging from -0.54 to 1.39 mv, and encapsulation efficiency is high (80 %). The stability of rhEPO was improved significantly in composite micelles in vitro. Pharmacokinetic studies in rats showed significant, enhanced plasma retention of the composite micelles in comparison with native rhEPO. Areas under curve (AUCs) of the rhEPO released from the composite micelles were 4.5- and 2.3-folds higher than those of the native rhEPO and rhEPO-loaded PEG-PLA micelle, respectively. In addition, the composite micelles exhibited good biocompatibility using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293T) cells. All these features are preferable for utilizing the composite micelles as a novel protein delivery system.

  15. Location of ethanol in sodium dodecyl sulfate aggregates

    LIU, Tian-Qing; YU, Wei-Li; GUO, Rong


    The hexagonal liquid crystalline phase of SDS ( Sodium dodecyl sulfate)/H2O system changes into lamellar liquid crystal and the effective length of surfactant molecule d0/2 in the lamellar liquid crystal decreases with the addition of ethanol.The micellar aggregation number N of SDS decreases and the micellar diffusion coefficient increases with the added ethanol.Under a constant concentration of SDS, the molecule number ratio of ethanol to SDS in the micelle increases with the concentration of ethanol and even exceeds 10 when ethanol concentration is 1.085 mol/L. All these results show that ethanol, even though a short chain alcohol and soluble in water, can partly exist in the interphase of the amphiphilic aggregates showing some properties of co-surfactant.

  16. Study on the Radius of an Electrical Spherical Micelle:Functional Theoretical Approach

    WANG,Zheng-Wu(王正武); HUANG,Dong-Yang(黄东阳); YI,Xi-Zhang(易希璋); LI,Gan-Zuo(李干佐)


    For the purpose of eliminating restriction,the Poisson-Boltzmann(PB)equation,which represents the potential of the electrical double layer of spherical micelles,can be solved analytically only under the lower potential condition,a kind of iterative method in functional analysis theory has been used.The radius of the spherical particle can be obtained from the diagram of the second iterative solution of the potential versus the distance from the center of the particle.The influences of the concentration of the ions,the charge number of ions,the aggregation number of the particle,the dielectric constant of solvent and the temperature of system on the radius also have been studied.

  17. Effect of lipophilic tail architecture and solvent engineering on the structure of trehalose-based nonionic surfactant reverse micelles.

    Shrestha, Lok Kumar; Sato, Takaaki; Dulle, Martin; Glatter, Otto; Aramaki, Kenji


    We use small-angle X-ray scattering and dynamic light scattering to investigate the structural and dynamical properties of trehalose polyisostearate, abbreviated as TQ-n (n = 3, 5, and 7), in different organic solvents, where n represents the number of isosterate chains per surfactant molecule. TQ-n spontaneously assembles into reverse micelles without addition of water at 25 °C. We found that for TQ-5 and TQ-7, steric hindrance of the lipophilic surfactant tail causes significant reduction of the aggregation number, whose scheme is clearly distinguished from the modification of the critical packing parameter. Increasing the hydrocarbon chain length of oils from octane to hexadecane favors one-dimensional micellar growth, leading to the formation of rodlike micelles due to different penetration tendencies of oils into the lipophilic shell of the surfactant. Subtle differences in solvent polarity also plays a crucial role in the micellar size, which is decreased when liquid paraffin is replaced with squalene. A further decrease is attained in more polar mixed triglyceride oils. A rising temperature also results in the same direction. The extrapolated structure factor to the zero scattering vector, S(q → 0), for the TQ-3/decane systems almost exactly follows that predicted for hard spheres, demonstrating that osmotic compressibility of the system is well explained if accounting for the excluded volume. However, we found that the effective diffusion coefficient decreases with surfactant concentration, which is an opposite trend to what is expected for hard spheres. This apparent contradiction is likely to be due to the occurrence of transient interdigitation between the lipophilic tails of neighboring reverse micelles at higher concentration. Our data highlight the relevance of the concept of "tunable reverse micellar geometry" in the novel trehalose-based nonionic surfactant binary mixtures, in which lipophilic tail architecture, solvent engineering, concentration

  18. Application of computer simulation free-energy methods to compute the free energy of micellization as a function of micelle composition. 1. Theory.

    Stephenson, Brian C; Stafford, Kate A; Beers, Kenneth J; Blankschtein, Daniel


    The widespread use of surfactant mixtures and surfactant/solubilizate mixtures in practical applications motivates the development of predictive theoretical approaches to improve fundamental understanding of the behavior of these complex self-assembling systems and to facilitate the design and optimization of new surfactant and surfactant/solubilizate mixtures. This paper is the first of two articles introducing a new computer simulation-free-energy/molecular thermodynamic (CS-FE/MT) model. The two articles explore the application of computer simulation free-energy methods to quantify the thermodynamics associated with mixed surfactant/cosurfactant and surfactant/solubilizate micelle formation in aqueous solution. In this paper (article 1 of the series), a theoretical approach is introduced to use computer simulation free-energy methods to compute the free-energy change associated with changing micelle composition (referred to as DeltaDeltaGi). In this approach, experimental critical micelle concentration (CMC) data, or a molecular thermodynamic model of micelle formation, is first used to evaluate the free energy associated with single (pure) surfactant micelle formation, g(form,single), in which the single surfactant micelle contains only surfactant A molecules. An iterative approach is proposed to combine the estimated value of gform,single with free-energy estimates of DeltaDeltaGi based on computer simulation to determine the optimal free energy of mixed micelle formation, the optimal micelle aggregation number and composition, and the optimal bulk solution composition. After introducing the CS-FE/MT modeling framework, a variety of free-energy methods are briefly reviewed, and the selection of the thermodynamic integration free-energy method is justified and selected to implement the CS-FE/MT model. An alchemical free-energy pathway is proposed to allow evaluation of the free-energy change associated with exchanging a surfactant A molecule with a surfactant

  19. Atomic Model and Micelle Dynamics of QS-21 Saponin

    Conrado Pedebos


    Full Text Available QS-21 is a saponin extracted from Quillaja saponaria, widely investigated as a vaccine immunoadjuvant. However, QS-21 use is mainly limited by its chemical instability, significant variety in molecular composition and low tolerance dose in mammals. Also, this compound tends to form micelles in a concentration-dependent manner. Here, we aimed to characterize its conformation and the process of micelle formation, both experimentally and computationally. Therefore, molecular dynamics (MD simulations were performed in systems containing different numbers of QS-21 molecules in aqueous solution, in order to evaluate the spontaneous micelle formation. The applied methodology allowed the generation of micelles whose sizes were shown to be in high agreement with small-angle X-ray scattering (SAXS. Furthermore, the ester linkage between fucose and acyl chain was less solvated in the micellar form, suggesting a reduction in hydrolysis. This is the first atomistic interpretation of previous experimental data, the first micellar characterization of saponin micelles by SAXS and first tridimensional model of a micelle constituted of saponins, contributing to the understanding of the molecular basis of these compounds.

  20. Therapeutic surfactant-stripped frozen micelles

    Zhang, Yumiao; Song, Wentao; Geng, Jumin; Chitgupi, Upendra; Unsal, Hande; Federizon, Jasmin; Rzayev, Javid; Sukumaran, Dinesh K.; Alexandridis, Paschalis; Lovell, Jonathan F.


    Injectable hydrophobic drugs are typically dissolved in surfactants and non-aqueous solvents which can induce negative side-effects. Alternatives like `top-down' fine milling of excipient-free injectable drug suspensions are not yet clinically viable and `bottom-up' self-assembled delivery systems usually substitute one solubilizing excipient for another, bringing new issues to consider. Here, we show that Pluronic (Poloxamer) block copolymers are amenable to low-temperature processing to strip away all free and loosely bound surfactant, leaving behind concentrated, kinetically frozen drug micelles containing minimal solubilizing excipient. This approach was validated for phylloquinone, cyclosporine, testosterone undecanoate, cabazitaxel and seven other bioactive molecules, achieving sizes between 45 and 160 nm and drug to solubilizer molar ratios 2-3 orders of magnitude higher than current formulations. Hypertonic saline or co-loaded cargo was found to prevent aggregation in some cases. Use of surfactant-stripped micelles avoided potential risks associated with other injectable formulations. Mechanistic insights are elucidated and therapeutic dose responses are demonstrated.

  1. Extraction of lysozyme, alpha-chymotrypsin, and pepsin into reverse micelles formed using an anionic surfactant, isooctane, and water.

    Chang, Q; Liu, H; Chen, J


    The extraction of lysozyme, alpha-chymotrypsin, and pepsin from buffered salt solutions into reverse micelles was examined at different pH values and surfactant concentrations. The reverse micelles was formed by mixing aqueous buffer supplemented with KCl and an organic phase of isooctane(2,2,4-trimethylpentane), containing the anionic surfactant, Aerosol O. T. (dioctyl ester of sodium sulfosuccinic acid). The technique of dynamic laser scattering was used to measure the size of reverse micelles which were in equilibrium with the aqueous phase. It was found that the size of the reverse micelles decreased with increasing ionic strength but increased with increasing AOT concentration. In the process of extraction, the reverse micelles might have rearranged themselves to host the protein. The sizes of protein-filled and -unfilled reverse micelles were different, and an open equilibrium could be reached between them. Under the extraction conditions, only a small number of micelles were found to contain protein.

  2. Crystalline free energies of micelles of diblock copolymer solutions

    D'Adamo, Giuseppe; 10.1063/1.3509391


    We report a characterization of the relative stability and structural behavior of various micellar crystals of an athermal model of AB-diblock copolymers in solution. We adopt a previously devel- oped coarse-graining representation of the chains which maps each copolymer on a soft dumbbell. Thanks to this strong reduction of degrees of freedom, we are able to investigate large aggregated systems, and for a specific length ratio of the blocks f = MA/(MA + MB) = 0.6, to locate the order-disorder transition of the system of micelles. Above the transition, mechanical and thermal properties are found to depend on the number of particles per lattice site in the simulation box, and the application of a recent methodology for multiple occupancy crystals (B.M. Mladek et al., Phys. Rev. Lett. 99, 235702 (2007)) is necessary to correctly define the equilibrium state. Within this scheme we have performed free energy calculations at two reduced density {\\rho}/{\\rho}\\ast = 4,5 and for several cubic structures as FCC,BCC,A1...

  3. Molecular aggregation of humic substances

    Wershaw, R. L.


    Humic substances (HS) form molecular aggregates in solution and on mineral surfaces. Elucidation of the mechanism of formation of these aggregates is important for an understanding of the interactions of HS in soils arid natural waters. The HS are formed mainly by enzymatic depolymerization and oxidation of plant biopolymers. These reactions transform the aromatic and lipid plant components into amphiphilic molecules, that is, molecules that consist of separate hydrophobic (nonpolar) and hydrophilic (polar) parts. The nonpolar parts of the molecules are composed of relatively unaltered segments of plant polymers and the polar parts of carboxylic acid groups. These amphiphiles form membrane-like aggregates on mineral surfaces and micelle-like aggregates in solution. The exterior surfaces of these aggregates are hydrophilic, and the interiors constitute separate hydrophobic liquid-like phases.

  4. An improvement of a beam search method for warehouse storage allocation planning problems minimizing the number of operations and the aggregated number of products for each customer

    Nishi, Tatsushi; Yamamoto, Shinichiro; Konishi, Masami

    The storage allocation planning problem in warehouse management is to determine the allocation of products to the storage space and intermediate operations for retrieving products so as to minimize the number of operations, and maximize the collected number of products for each customer when the sequence of requests for inlet and retrieval operations are given. In this paper, we propose an efficient beam search method for generating a near optimal solution with a reasonable computation time. A heuristic procedure is also proposed in order to reduce a search space in the beam search method by using the information of subsequent inlet and retrieving requests. The validity of the proposed method is confirmed by comparing the results with the optimal solution derived by solving an MILP problem. The effectiveness of the proposed method is demonstrated by solving an actual large-sized problem consisting of more than 3000 operations.

  5. How to squeeze a sponge: casein micelles under osmotic stress, a SAXS study.

    Bouchoux, Antoine; Gésan-Guiziou, Geneviève; Pérez, Javier; Cabane, Bernard


    By combining the osmotic stress technique with small-angle x-ray scattering measurements, we followed the structural response of the casein micelle to an overall increase in concentration. When the aqueous phase that separates the micelles is extracted, they behave as polydisperse repelling spheres and their internal structure is not affected. When they are compressed, the micelles lose water and shrink to a smaller volume. Our results indicate that this compression is nonaffine, i.e., some parts of the micelle collapse, whereas other parts resist deformation. We suggest that this behavior is consistent with a spongelike casein micelle having a triple hierarchical structure. The lowest level of the structure consists of the CaP nanoclusters that serve as anchors for the casein molecules. The intermediate level consists of 10- to 40-nm hard regions that resist compression and contain the nanoclusters. Those regions are connected and/or partially merged with each other, thus forming a continuous and porous material. The third level of structure is the casein micelle itself, with an average size of 100 nm. In our view, such a structure is consistent with the observation of 10- to 20-nm casein particles in the Golgi vesicles of lactating cells: upon aggregation, those particles would rearrange, fuse, and/or swell to form the spongelike micelle.

  6. The fine-tuning of thermosensitive and degradable polymer micelles for enhancing intracellular uptake and drug release in tumors.

    Li, Wei; Li, Jinfeng; Gao, Jie; Li, Bohua; Xia, Yu; Meng, Yanchun; Yu, Yongsheng; Chen, Huaiwen; Dai, Jianxin; Wang, Hao; Guo, Yajun


    Focusing on high temperature and low pH of tumor tissue, we prepared temperature and pH responsive poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-lacitde) (PID(118)-b-PLA(59)) and poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide-b-ε-caprolactone) (PID(118)-b-PCL(60)) diblock copolymers with symmetric hydrophobic blocks by the reversible addition-fragmentation chain transfer (RAFT). The corresponding dual functional polymeric micelles were fabricated by dialysis methods. Their well-defined core-shell structure was characterized by (1)H NMR in D(2)O and further confirmed by TEM. Their structural and physical chemistry properties such as diameters (D), core corona dimension (R(core), R(shell)), distribution (PDI), M(w), aggregation number (N(agg)), second virial coefficient (A(2)), critical micellization concentration (CMC) and z-potential were firstly systemically investigated by dynamic and static laser light scattering. The volume phase transition temperature (VPTT) was around 40 °C above which the intracellular uptake of adriamycin (ADR) was significantly enhanced. Both flow cytometry and fluorescent microscopy showed that the ADR transported by these micelles was about 4 times higher than that by the commercial ADR formulation Taxotere®. In vitro cytotoxicity assay against N-87 cancer cell and confocal laser scanning microscopy (CLSM) also confirmed such promoting efficiency. In addition, it was interesting to find that cell surviving bounced back as T = 42 °C due to the inter-micellar aggregation. The well clarified mechanism strongly support that our finely tailored dual functional core-shell micelles are potent in enhancing cellular uptake and drug release.

  7. New Strategies for Constructing Polymeric Micelles and Hollow Spheres Via Self-Assembly

    Ming Jiang


    @@ 1Introduction In recent years, self-assembly of block copolymers leading to micelles in selective solvents, which dissolve only one of the blocks, has developed rapidly because the micelles are very strong candidates for potential applications in advanced technologies. The micelles usually have core-shell structure which are connected by covalent bonds. Based on our long-term research on interpolymer complexation due to hydrogen bonding, where we noticed that the complexation often led to the formation of irregular aggregates, we succeeded recently in developing a series of new approaches to polymeric micelles and hollow spheres via specific intermolecular interactions. As in these approaches, a variety of polymers with interacting groups i.e. homopolymers, random copolymers, graft copolymers as well as low mass compounds (LMC), can be used as building blocks, our research strategies have substantially extended the field of self-assembly.

  8. Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle

    Shi YN


    Full Text Available Yanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd, Yantai, China; 3School of Pharmacy, Yantai University, Yantai, China*These authors contributed equally to this workAbstract: To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO, rhEPO was successfully formulated into poly(ethylene glycol–poly(d,l-lactide (PEG–PLA di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3 and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.Keywords: rhEPO, PEG–PLA micelle, in vitro, pharmacokinetics, pharmacodynamics

  9. Thermodynamics of hexadecyltrimethylammonium bromide micelle formation

    Velikov, A. A.


    The thermodynamic parameters for CTAB micelle formation (Δ H, Δ G, Δ S) are calculated at different temperatures. Critical micelle concentrations CMC1 are determined. The possibility of determining CMC2 is demonstrated.

  10. Achieving micelle control through core crystallinity.

    Glavas, Lidija; Olsén, Peter; Odelius, Karin; Albertsson, Ann-Christine


    We have designed a pathway for controlling the critical micelle concentration and micelle size of polyester-based systems. This was achieved by creating an array of different copolymers with semicrystalline or amorphous hydrophobic blocks. The hydrophobic block was constructed through ring-opening polymerization of ε-caprolactone, L-lactide, and ε-decalactone, either as homopolymers or random copolymers, using PEG as both the initiator and the hydrophilic block. Micelles formed with amorphous cores exhibited considerably higher critical micelle concentrations than those with semicrystalline cores. Micelles with amorphous cores also became larger in size with an increased molecular weight of the hydrophobic bock, in contrast to micelles with semicrystalline cores, which displayed the opposite behavior. Hence, core crystallinity was found to be a potent tool for tailoring micelle properties and thereby facilitating the optimization of drug delivery systems. The introduction of PEG-PεDL also proved to be a valuable asset in the tuning of micelle properties.

  11. From micelle supramolecular assemblies in selective solvents to isoporous membranes.

    Nunes, Suzana P; Karunakaran, Madhavan; Pradeep, Neelakanda; Behzad, Ali Reza; Hooghan, Bobby; Sougrat, Rachid; He, Haoze; Peinemann, Klaus-Viktor


    The supramolecular assembly of PS-b-P4VP copolymer micelles induced by selective solvent mixtures was used to manufacture isoporous membranes. Micelle order in solution was confirmed by cryo-scanning electron microscopy in casting solutions, leading to ordered pore morphology. When dioxane, a solvent that interacts poorly with the micelle corona, was added to the solution, polymer-polymer segment contact was preferential, increasing the intermicelle contact. Immersion in water gave rise to asymmetric porous membranes with exceptional pore uniformity and high porosity. The introduction of a small number of carbon nanotubes to the casting solution improved the membrane stability and the reversibility of the gate response in the presence of different pH values.

  12. From micelle supramolecular assemblies in selective solvents to isoporous membranes

    Nunes, Suzana Pereira


    The supramolecular assembly of PS-b-P4VP copolymer micelles induced by selective solvent mixtures was used to manufacture isoporous membranes. Micelle order in solution was confirmed by cryo-scanning electron microscopy in casting solutions, leading to ordered pore morphology. When dioxane, a solvent that interacts poorly with the micelle corona, was added to the solution, polymer-polymer segment contact was preferential, increasing the intermicelle contact. Immersion in water gave rise to asymmetric porous membranes with exceptional pore uniformity and high porosity. The introduction of a small number of carbon nanotubes to the casting solution improved the membrane stability and the reversibility of the gate response in the presence of different pH values. © 2011 American Chemical Society.

  13. Casein micelles: size distribution in milks from individual cows.

    de Kruif, C G Kees; Huppertz, Thom


    The size distribution and protein composition of casein micelles in the milk of Holstein-Friesian cows was determined as a function of stage and number of lactations. Protein composition did not vary significantly between the milks of different cows or as a function of lactation stage. Differences in the size and polydispersity of the casein micelles were observed between the milks of different cows, but not as a function of stage of milking or stage of lactation and not even over successive lactations periods. Modal radii varied from 55 to 70 nm, whereas hydrodynamic radii at a scattering angle of 73° (Q² = 350 μm⁻²) varied from 77 to 115 nm and polydispersity varied from 0.27 to 0.41, in a log-normal distribution. Casein micelle size in the milks of individual cows was not correlated with age, milk production, or lactation stage of the cows or fat or protein content of the milk.

  14. Effects of architecture on the stability of thermosensitive unimolecular micelles.

    Steinschulte, Alexander A; Schulte, Bjoern; Rütten, Stephan; Eckert, Thomas; Okuda, Jun; Möller, Martin; Schneider, Stefanie; Borisov, Oleg V; Plamper, Felix A


    The influence of architecture on polymer interactions is investigated and differences between branched and linear copolymers are found. A comprehensive picture is drawn with the help of a fluorescence approach (using pyrene and 4HP as probe molecules) together with IR or NMR spectroscopy and X-ray/light scattering measurements. Five key aspects are addressed: (1) synergistic intramolecular complexation within miktoarm stars. The proximity of thermoresponsive poly(propylene oxide) (PPO) and poly(dimethylaminoethyl methacrylate) (PDMAEMA) within a miktoarm star leads to complexation between these weakly interacting partners. Consequently, the original properties of the constituents are lost, showing hydrophobic domains even at low temperatures, at which all homopolymers are water soluble. (2) Unimolecular micelles for miktoarm stars. The star does not exhibit intermolecular self-assembly in a large temperature range, showing unimers up to 55 °C. This behavior was traced back to a reduced interfacial tension between the PPO-PDMAEMA complex and water (PDMAEMA acts as a "microsurfactant"). (3) Unimolecular to multimolecular micelle transition for stars. The otherwise stable unimolecular micelles self-assemble above 55 °C. This aggregation is not driven by PPO segregation, but by collapse of residual PDMAEMA. This leads to micrometer-sized multilamellar vesicles stabilized by poly(ethylene oxide) (PEO). (4) Prevention of pronounced complexation within diblock copolymers. In contrast to the star copolymers, PPO and PDMAEMA adapt rather their homopolymer behavior within the diblock copolymers. Then they show their immanent LCST properties, as PDMAEMA turns insoluble at elevated temperatures, whereas PPO becomes hydrophobic below room temperature. (5) Two-step micellization for diblock copolymers. Upon heating of linear copolymers, the dehydration of PPO is followed by self-assembly into spherical micelles. An intermediate prevalence of unimolecular micelles is revealed

  15. Casein Micelles: Size Distribution in Milks from Individual Cows

    de Kruif, C.G.; Huppertz, T.


    The size distribution and protein composition of casein micelles in the milk of Holstein-Friesian cows was determined as a function of stage and number of lactations. Protein composition did not vary significantly between the milks of different cows or as a function of lactation stage. Differences i

  16. Interfacial properties, thin film stability and foam stability of casein micelle dispersions

    Chen, Min; Sala, G.; Meinders, M.B.J.; Valenberg, van H.J.F.; Linden, van der E.; Sagis, L.M.C.


    Foam stability of casein micelle dispersions (CMDs) strongly depends on aggregate size. To elucidate the underlying mechanism, the role of interfacial and thin film properties was investigated. CMDs were prepared at 4 °C and 20 °C, designated as CMD4 °C and CMD20 °C. At equal protein concentrations,

  17. Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

    Leonhard, Victoria; Alasino, Roxana V; Bianco, Ismael D; Garro, Ariel G; Heredia, Valeria; Beltramo, Dante M


    Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. PMID:26005348

  18. Preparation and Characterization of Copolymer Micelles Formed by Poly(ethylene glycol)-Polylactide Block Copolymers as Novel Drug Carriers

    姜维; 王运东; 甘泉; 张建铮; 赵秀文; 费维扬; 贝建中; 王身国


    Diblock copolymer poly(ethylene glycol) methyl ether-polylactide (MePEG-PLA) micelles were prepared by dialysis against water. Indomethacin (IMC) as a model drug was entrapped into the micelles by dialysis method. The critical micelle concentration (CMC) of the prepared micelles in distilled water investigated by fluorescence spectroscopy was 0.0051mg/mL which is lower than that of common low molecular weight surfactants. The diameters of MePEG-PLA micelles and IMC loaded MePEG-PLA micelles in a number-averaged scale measured by dynamic light scattering were 52.4 and 53.7 nm respectively. The observation with transmission electron microscope and scanning electron microscope showed that the appearance of MePEG-PLA micelles was in a spherical shape. The content of IMC incorporated in the core portion of the micelles was 18% (ω). The effects of the synthesis method of the copolymer on the polydispersity of the micelles and the yield of the micelles formation were discussed.

  19. Preparation of stable spherical micelles with rigid backbones based on polyaryletherketone copolymers containing lateral pyridyl groups

    Zhang, Shuling; Liu, Lingzhi; Guo, Yunliang; Jiang, Zhenhua; Wang, Guibin, E-mail:


    A new bisphenol monomer, 3-(3,4-dihydroxyphenylimine) pyridine (PYPH), was synthesized via a deoxidization reaction of an amine. A series of novel polyaryletherketone copolymers containing lateral pyridyl groups (PY-PAEKs) based on PYPH, 2,2-di(4-hydroxyphenyl)propane and 4,4′-difluorobenzophenone were prepared by nucleophilic aromatic substitution polycondensation reactions. Furthermore, spherical micelles with rigid PY-PAEKs as the inner cores and flexible polyacrylic acid (PAA) as the outer shells were obtained in a selective solvent (H{sub 2}O) successfully. The formation of the spherical micelles was confirmed by scanning electron and transmission electron microscopy as well as by surface tension measurements. The formation and size of the spherical micelles depended on the weight ratio of PAA/PY-PAEK, the concentration and pH value of the mixed solution containing the PY-PAEK and PAA, and the number of pyridyl groups in the PY-PAEK. The structure of the spherical micelles could be stabilized by a cross-linking reaction between the pyridyl groups of the PY-PAEKs and 1,4-dibromobutane. The diameter of the spherical micelles decreased because of the removal of the PAA shell from the PY-PAEK core after the cross-linking reaction. The resulting stable spherical micelles with rigid backbones did not dissolve in a number of polar solvents and remained unaffected by changes in the pH values. - Graphical abstract: Display Omitted - Highlights: • Polyaryletherketone copolymers containing lateral pyridyl groups were synthesized. • Spherical micelles were prepared using these copolymers and polyacrylic acid. • The copolymers and polyacrylic acid formed the core and the shell of the micelles, respectively. • The obtained micelles were stabilized by a cross-linking reaction. • The cross-linked micelles had rigid backbones, independent of solvents and pH values.

  20. Dielectric relaxation spectroscopy shows a sparingly hydrated interface and low counterion mobility in triflate micelles.

    Lima, Filipe S; Chaimovich, Hernan; Cuccovia, Iolanda M; Buchner, Richard


    The properties of ionic micelles are affected by the nature of the counterion. Specific ion effects can be dramatic, inducing even shape and phase changes in micellar solutions, transitions apparently related to micellar hydration and counterion binding at the micellar interface. Thus, determining the hydration and dynamics of ions in micellar systems capable of undergoing such transitions is a crucial step in understanding shape and phase changes. For cationic micelles, such transitions are common with large organic anions as counterions. Interestingly, however, phase separation also occurs for dodecyltrimethylammonium triflate (DTATf) micelles in the presence of sodium triflate (NaTf). Specific ion effects for micellar solutions of dodecyltrimethylammonium chloride (DTAC), bromide (DTAB), methanesulfonate (DTAMs), and triflate (DTATf) were studied with dielectric relaxation spectroscopy (DRS), a technique capable of monitoring hydration and counterion dynamics of micellar aggregates. In comparison to DTAB, DTAC, and DTAMs, DTATf micelles were found to be considerably less hydrated and showed reduced counterion mobility at the micellar interface. The obtained DTATf and DTAMs data support the reported central role of the anion's -CF3 moiety with respect to the properties of DTATf micelles. The reduced hydration observed for DTATf micelles was rationalized in terms of the higher packing of this surfactant compared to that of other DTA-based systems. The decreased mobility of Tf(-) anions condensed at the DTATf interface strongly suggests the insertion of Tf(-) in the micellar interface, which is apparently driven by the strong hydrophobicity of -CF3.

  1. Bioreducible unimolecular micelles based on amphiphilic multiarm hyperbranched copolymers for triggered drug release


    A novel type of bioreducible amphiphilic multiarm hyperbranched copolymer (H40-star-PLA-SS-PEG) based on Boltorn H40 core,poly(L-lactide) (PLA) inner-shell,and poly(ethylene glycol) (PEG) outer-shell with disulfide-linkages between the hydrophobic and hydrophilic moieties was developed as unimolecular micelles for controlled drug release triggered by reduction.The obtained H40-star-PLA-SS-PEG was characterized in detail by nuclear magnetic resonance (NMR),Fourier transform infrared (FTIR),gel permeation chromatography (GPC),differential scanning calorimeter (DSC),and thermal gravimetric analysis (TGA).Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analyses suggested that H40-star-PLA-SS-PEG formed stable unimolecular micelles in aqueous solution with an average diameter of 19 nm.Interestingly,these micelles aggregated into large particles rapidly in response to 10 mM dithiothreitol (DTT),most likely due to shedding of the hydrophilic PEG outer-shell through reductive cleavage of the disulfide bonds.As a hydrophobic anticancer model drug,doxorubicin (DOX) was encapsulated into these reductive unimolecular micelles.In vitro release studies revealed that under the reduction-stimulus,the detachment of PEG outer-shell in DOX-loaded micelles resulted in a rapid drug release.Flow cytometry and confocal laser scanning microscopy (CLSM) measurements indicated that these DOX-loaded micelles were easily internalized by living cells.Methyl tetrazolium (MTT) assay demonstrated a markedly enhanced drug efficacy of DOX-loaded H40-star-PLA-SS-PEG micelles as compared to free DOX.All of these results show that these bioreducible unimolecular micelles are promising carriers for the triggered intracellular delivery of hydrophobic anticancer drugs.

  2. Multicompartmental Microcapsules from Star Copolymer Micelles

    Choi, Ikjun; Malak, Sidney T.; Xu, Weinan; Heller, William T.; Tsitsilianis, Constantinos; Tsukruk, Vladimir V.


    We present the layer-by-layer (LbL) assembly of amphiphilic heteroarm pH-sensitive star-shaped polystyrene-poly(2-pyridine) (PSnP2VPn) block copolymers to fabricate porous and multicompartmental microcapsules. Pyridine-containing star molecules forming a hydrophobic core/hydrophilic corona unimolecular micelle in acidic solution (pH 3) were alternately deposited with oppositely charged linear sulfonated polystyrene (PSS), yielding microcapsules with LbL shells containing hydrophobic micelles. The surface morphology and internal nanopore structure of the hollow microcapsules were comparatively investigated for shells formed from star polymers with a different numbers of arms (9 versus 22) and varied shell thickness (5, 8, and 11 bilayers). The successful integration of star unimers into the LbL shells was demonstrated by probing their buildup, surface segregation behavior, and porosity. The larger arm star copolymer (22 arms) with stretched conformation showed a higher increment in shell thickness due to the effective ionic complexation whereas a compact, uniform grainy morphology was observed regardless of the number of deposition cycles and arm numbers. Small-angle neutron scattering (SANS) revealed that microcapsules with hydrophobic domains showed different fractal properties depending upon the number of bilayers with a surface fractal morphology observed for the thinnest shells and a mass fractal morphology for the completed shells formed with the larger number of bilayers. Moreover, SANS provides support for the presence of relatively large pores (about 25 nm across) for the thinnest shells as suggested from permeability experiments. The formation of robust microcapsules with nanoporous shells composed of a hydrophilic polyelectrolyte with a densely packed hydrophobic core based on star amphiphiles represents an intriguing and novel case of compartmentalized microcapsules with an ability to simultaneously store different hydrophilic, charged, and hydrophobic

  3. Hydrotropy: monomer-micelle equilibrium and minimum hydrotrope concentration.

    Shimizu, Seishi; Matubayasi, Nobuyuki


    Drug molecules with low aqueous solubility can be solubilized by a class of cosolvents, known as hydrotropes. Their action has often been explained by an analogy with micelle formation, which exhibits critical micelle concentration (CMC). Indeed, hydrotropes also exhibit "minimum hydrotrope concentration" (MHC), a threshold concentration for solubilization. However, MHC is observed even for nonaggregating monomeric hydrotropes (such as urea); this raises questions over the validity of this analogy. Here we clarify the effect of micellization on hydrotropy, as well as the origin of MHC when micellization is not accompanied. On the basis of the rigorous Kirkwood-Buff (KB) theory of solutions, we show that (i) micellar hydrotropy is explained also from preferential drug-hydrotrope interaction; (ii) yet micelle formation reduces solubilization effeciency per hydrotrope molecule; (iii) MHC is caused by hydrotrope-hydrotrope self-association induced by the solute (drug) molecule; and (iv) MHC is prevented by hydrotrope self-aggregation in the bulk solution. We thus need a departure from the traditional view; the structure of hydrotrope-water mixture around the drug molecule, not the structure of the aqueous hydrotrope solutions in the bulk phase, is the true key toward understanding the origin of MHC.

  4. Aggregate Formed by a Cationic Fluorescence Probe

    TIAN, Juan; SANG, Da-Yong; JI, Guo-Zhen


    The aggregation behavior of a cationic fluorescence probe 10-(4,7,10,13,16-pentaoxa-1-azacyclooctadecyl-methyl)anthracen-9-ylmethyl dodecanoate (1) was observed and studied by a fluorescence methodology in acidic and neutral conditions. By using the Py scale, differences between simple aggregates and micelles have been discussed. The stability of simple aggregates was discussed in terms of hydrophobic interaction and electrostatic repulsion. The absence of excimer emission of the anthrancene moiety of probe 1 in neutral condition was attributed to the photoinduced electron transfer mechanism instead of photodimerization.

  5. Molecular Simulation of Reverse Micelles

    Chowdhary, Janamejaya; Ladanyi, Branka


    Reverse micelles (RM) are surfactant assemblies containing a nanosized water pool dissolved in a hydrophobic solvent. Understanding their properties is crucial for insight into the effect of confinement on aqueous structure, dynamics as well as physical processes associated with solutes in confinement. We perform molecular dynamics simulations for the RM formed by the surfactant Aerosol-OT (AOT) in isooctane (2,2,4-trimethyl pentane) in order to study the effect of reverse micelle size on the aqueous phase. The structure of the RM is quantified in terms of the radial and pair density distributions. Dynamics are studied in terms of the mean squared displacements and various orientational time correlation functions in different parts of the RM so as to understand the effect of proximity to the interface on aqueous dynamics. Shape fluctuations of the RM are also analyzed.

  6. Dynamics of Chain Exchange in Block Copolymer Micelles

    Lodge, Timothy

    Block copolymer micelles are rarely at equilibrium. The primary reason is the large number of repeat units in the insoluble block, Ncore, which makes the thermodynamic penalty for extracting a single chain (``unimer exchange'') substantial. As a consequence, the critical micelle concentration (CMC) is rarely accessed experimentally; however, in the proximity of a critical micelle temperature (CMT), equilibration is possible. We have been using time-resolved small angle neutron scattering (TR-SANS) to obtain a detailed picture of the mechanisms and time scales for chain exchange, at or near equilibrium. Our model system is poly(styrene)-block-poly(ethylene-alt-propylene)) (PS-PEP), in the PEP-selective solvent squalane (C30H62) . Equivalent micelles with either normal (hPS) or perdeuterated (dPS) cores are initially mixed in a blend of isotopically substituted squalane, designed to contrast-match a 50:50 hPS:dPS core. Samples are then annealed at a target temperature, and chain exchange is revealed quantitatively by the temporal decay in scattered intensity. The rate of exchange as function of concentration, temperature, Ncore, Ncorona, and chain architecture (diblock versus triblock) will be discussed.

  7. Bioreducible Micelles Self-Assembled from Poly(ethylene glycol-Cholesteryl Conjugate As a Drug Delivery Platform

    Chulsu Baek


    Full Text Available The ability of polymeric micelles to self-assemble into nanosized particles has created interest in their application as potential anticancer drug delivery systems. A poly(ethylene glycol-cholesteryl conjugate (Chol-ss-PEG-ss-Chol connected by cleavable disulfide linkages was synthesized and used as a nanocarrier for in vitro release of doxorubicin (DOX. Owing to its amphiphilic structure, Chol-ss-PEG-ss-Chol was able to self-assemble into micelles with an average diameter 18.6 nm in aqueous solution. The micelles formed large aggregates due to the shedding of the PEG shell through cleavage of disulfide bonds in a reductive environment. The in vitro release studies revealed that Chol-ss-PEG-ss-Chol micelles released 80% and approximately 9% of the encapsulated DOX within 6 h under reductive and non-reductive conditions, respectively. The glutathione (GSH-mediated intracellular drug delivery was investigated in a KB cell line. The cytotoxicity of DOX-loaded micelles indicated a higher cellular anti-proliferative effect against GSH-pretreated than untreated KB cells. Furthermore, confocal laser scanning microscopy (CLSM measurement demonstrated that Chol-ss-PEG-ss-Chol micelles exhibited faster drug release in GSH-pretreated KB cells than untreated KB cells. These results suggest the potential usefulness of disulfide-based polymeric micelles as controlled drug delivery carriers.

  8. Ultrasound-Mediated Polymeric Micelle Drug Delivery.

    Xia, Hesheng; Zhao, Yue; Tong, Rui


    The synthesis of multi-functional nanocarriers and the design of new stimuli-responsive means are equally important for drug delivery. Ultrasound can be used as a remote, non-invasive and controllable trigger for the stimuli-responsive release of nanocarriers. Polymeric micelles are one kind of potential drug nanocarrier. By combining ultrasound and polymeric micelles, a new modality (i.e., ultrasound-mediated polymeric micelle drug delivery) has been developed and has recently received increasing attention. A major challenge remaining in developing ultrasound-responsive polymeric micelles is the improvement of the sensitivity or responsiveness of polymeric micelles to ultrasound. This chapter reviews the recent advance in this field. In order to understand the interaction mechanism between ultrasound stimulus and polymeric micelles, ultrasound effects, such as thermal effect, cavitation effect, ultrasound sonochemistry (including ultrasonic degradation, ultrasound-initiated polymerization, ultrasonic in-situ polymerization and ultrasound site-specific degradation), as well as basic micellar knowledge are introduced. Ultrasound-mediated polymeric micelle drug delivery has been classified into two main streams based on the different interaction mechanism between ultrasound and polymeric micelles; one is based on the ultrasound-induced physical disruption of the micelle and reversible release of payload. The other is based on micellar ultrasound mechanochemical disruption and irreversible release of payload.

  9. Multimodality CT/SPECT Evaluation of Micelle Drug Carriers for Treatment of Breast Tumors


    TEM), dynamic light scattering (DLS), and NMR to examine morphology, size, and drug encapsulation . The in vitro efficacy of the micelles was seen in Figure 2, β-lap PEG-PLA micelles were core-shell in nature, possessing a PEG hydrated layer on the surface, all the while encapsulating ...hydroxypropyl-β- cyclodextrin (HPβ-CD). However, the clinical trials show that a large number of patients suffer from high levels of hemolysis and anemia

  10. Preparation and Characterization of Polymeric Micelles from Poly(D,L-lactide) and Methoxypolyethylene Glycol Block Copolymers as Potential Drug Carriers


    Amphiphilic diblock copolymers composed of methoxy polyethylene glycol (MePEG) and poly(D,L-lactide) (PDLLA) were prepared for the preparation of polymeric micelles. The use of MePEG-PDLLA as drug carriers has been reported in the open literature, but there are only few data on the application of a series of MePEG-PDLLA copolymers with different lengths in the medical field. The shape of the polymeric micelles is also important in drug delivery. Studies on in vitro drug release profiles require a good sink condition. The critical micelle concentration of a series of MePEG-PDLLA has a significant role in drug release. To estimate their feasibility as a drug carrier, polymeric micelles made of MePEG-PDLLA block copolymer were prepared by the oil in water (O/W) emulsion method. From dynamic light scattering (DLS) measurements,the size of the micelle formed was less than 200 nm. The critical micelle concentration of polymeric micelles with various compositions was determined using pyrene as a fluorescence probe. The critical micelle concentration decreased with increasing number of hydrophobic segments. MePEG-PDLLA micelles have a considerably low critical micelle concentration (0.4-0.5 μg/mL), which is apparently an advantage in utilizing these micelles as drug carriers. The morphology of the polymeric micelles was observed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The micelles were found to be nearly spherical. The yield of the polymeric micelles obtained from the ONV method is as high as 85%.

  11. Temperature and pressure based NMR studies of detergent micelle phase equilibria.

    Alvares, Rohan; Gupta, Shaan; Macdonald, Peter M; Prosser, R Scott


    Bulk thermodynamic and volumetric parameters (ΔGmic°, ΔHmic°, ΔSmic°, ΔCp,mic°, ΔVmic°, and Δκmic°) associated with the monomer–micelle equilibrium, were directly determined for a variety of common detergents [sodium n-dodecyl sulfate (SDS), n-dodecyl phosphocholine (DPC), n-dodecyl-β-d-maltoside (DDM), and 7-cyclohexyl-1-heptyl phosphocholine (CyF)] via 1H NMR spectroscopy. For each temperature and pressure point, the critical micelle concentration (cmc) was obtained from a single 1H NMR spectrum at a single intermediate concentration by referencing the observed chemical shift to those of pure monomer and pure micellar phases. This permitted rapid measurements of the cmc over a range of temperatures and pressures. In all cases, micelle formation was strongly entropically favored, while enthalpy changes were all positive, with the exception of SDS, which exhibited a modestly negative enthalpy of micellization. Heat capacity changes were also characteristically negative, while partial molar volume changes were uniformly positive, as expected for an aggregation process dictated by hydrophobic effects. Isothermal compressibility changes were found to be consistent with previous measurements using other techniques. Thermodynamic measurements were also related to spectroscopic studies of topology and micelle structure. For example, paramagnetic effects resulting from the addition of dioxygen provided microscopic topological details concerning the hydrophobicity gradient along the detergent chains within their respective micelles as detected by 1H NMR. In a second example, combined 13C and 1H NMR chemical shift changes arising from application of high pressure, or upon micellization, of CyF provided site-specific details regarding micelle topology. In this fashion, bulk thermodynamics could be related to microscopic topological details within the detergent micelle.

  12. Investigations on the lyophilisation of MPEG-hexPLA micelle based pharmaceutical formulations.

    Di Tommaso, Claudia; Como, Caterina; Gurny, Robert; Möller, Michael


    Lyophilisation is a common procedure to increase the long-term stability of pharmaceutical formulations. Its applicability to polymeric micelles is usually an issue because of the aggregation of materials during freeze-drying steps. The feasibility of this process was studied on polymeric micelles based on methoxy poly(ethylene glycol)-poly(hexyl-lactide) (MPEG-hexPLA) with and without Cyclosporin A, in order to increase the stability of these pharmaceutical formulations. Freeze-thawing tests were carried out to determine the protective effect of various excipients on the freezing step. Mannitol, trehalose, glucose and sucrose showed the best effectiveness in micelle protection. The lyophilisation process was optimised by thermal analysis (DSC) on excipients to determine the glass transition temperature of the cryoconcentrate solutions (T(g)') and their glass transition temperature (T(g)). The freeze-dried powders were characterized in terms of morphology (SEM) and of moisture content (Karl Fisher titration). The reconstituted micelle formulations were analysed for size by DLS with and without goniometer, for morphology by TEM, for drug loading by HPLC. The formulation presenting the best characteristics before and after reconstitution contained 10% (w/v) sucrose in phosphate buffer. This lyophilised formulation was constituted of a brittle and white cake, with a residual water content of around 2% and it was easily reconstituted in a transparent and clear solution giving back a colloidal system with spherical micelles in the submicron range (study showed that the MPEG-hexPLA micelles can be efficiently lyophilised and this process can be usefully applied to increase the pharmaceutical stability of these pharmaceutical micelle formulations. 2010 Elsevier B.V. All rights reserved.

  13. Micelle-induced depletion interaction and resultant structure in charged colloidal nanoparticle system

    Ray, D.; Aswal, V. K., E-mail: [Solid State Physics Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India); Kohlbrecher, J. [Laboratory for Neutron Scattering, Paul Scherrer Institut, CH-5232 PSI Villigen (Switzerland)


    The evolution of the interaction and the resultant structure in the mixed system of anionic silica nanoparticles (Ludox LS30) and non-ionic surfactant decaethylene glycol monododecylether (C12E10), undergoing phase separation, have been studied using small-angle neutron scattering and dynamic light scattering. The measurements have been carried out for a fixed concentration of nanoparticle (1 wt. %) with varying concentration of surfactant (0 to 1 wt. %), in the absence and presence of an electrolyte. It is found that the micelles of non-ionic surfactant adsorb on the nanoparticle in the absence of electrolyte (form stable system), whereas these micelles become non-adsorbing in the presence of electrolyte (show phase separation). The phase separation arises because of C12E10 micelles, causing depletion interaction between nanoparticles and leading to their aggregation. The interaction is modeled by double Yukawa potential accounting for attractive depletion as well as repulsive electrostatic forces. Both the interactions (attraction and repulsion) are found to be of long-range. The nanoparticle aggregation (phase separation) is governed by the increase in the magnitude and the range of the depletion attraction with the increase in the surfactant concentration. The nanoparticle aggregates formed are quite large in size (order of micron) and are characterized by the surface fractal having simple cubic packing of nanoparticles within the aggregates.

  14. Interfacial properties, thin film stability and foam stability of casein micelle dispersions.

    Chen, Min; Sala, Guido; Meinders, Marcel B J; van Valenberg, Hein J F; van der Linden, Erik; Sagis, Leonard M C


    Foam stability of casein micelle dispersions (CMDs) strongly depends on aggregate size. To elucidate the underlying mechanism, the role of interfacial and thin film properties was investigated. CMDs were prepared at 4°C and 20°C, designated as CMD4°C and CMD20°C. At equal protein concentrations, foam stability of CMD4°C (with casein micelle aggregates) was markedly higher than CMD20°C (without aggregates). Although the elastic modulus of CMD4°C was twice as that of CMD20°C at 0.005Hz, the protein adsorbed amount was slightly higher for CMD20°C than for CMD4°C, which indicated a slight difference in interfacial composition of the air/water interface. Non-linear surface dilatational rheology showed minor differences between mechanical properties of air/water interfaces stabilized by two CMDs. These differences in interfacial properties could not explain the large difference in foam stability between two CMDs. Thin film analysis showed that films made with CMD20°C drained to a more homogeneous film compared to films stabilized by CMD4°C. Large casein micelle aggregates trapped in the thin film of CMD4°C made the film more heterogeneous. The rupture time of thin films was significantly longer for CMD4°C (>1h) than for CMD20°C (foam stability decreased significantly. In conclusion, the increased stability of foam prepared with CMD4°C appears to be the result of entrapment of casein micelle aggregates in the liquid films of the foam.

  15. Preparation of novel ferrocene-based shell cross-linked thermoresponsive hybrid micelles with antitumor efficacy.

    Wei, Hua; Quan, Chang-Yun; Chang, Cong; Zhang, Xian-Zheng; Zhuo, Ren-Xi


    The shell cross-linked (SCL) thermoresponsive hybrid poly(N-isopropylacrylamide-co-aminoethyl methacrylate)-b-polymethyl methacrylate (P(NIPAAm-co-AMA)-b-PMMA) micelle consisting of a cross-linked thermoresponsive hybrid shell and a hydrophobic core domain was fabricated via a two-step process: micellization of P(NIPAAm-co-AMA)-b-PMMA in aqueous solution followed by cross-linking of the hydrophilic shell layer via the amidation reaction between the amine groups of AMA units and the carboxylic acid functions of 1,1'-ferrocenedicarboxylic acid. The SCL micelle showed reversible dispersion/aggregation in response to the temperature cycles through the lower critical solution temperature (LCST) of the thermoresponsive hybrid shell at around 36 degrees C, observed by turbidity measurements and dynamic light scattering (DLS). Besides the usage as an inorganic difunctional cross-linker, the inorganic ferrocene segment further endowed the SCL hybrid micelle with the antitumor efficacy, namely, the resulting SCL micelle exhibited a remarkable cytotoxic effect for HeLa cells with a very low IC50. The results showed that the SCL hybrid micelle developed in this study could be potentially used as an antitumor agent, which is unique compared to the conventional tumor therapy by using the antitumor drug loaded in the micellar core.

  16. Small angle neutron scattering study of doxorubicin–surfactant complexes encapsulated in block copolymer micelles

    Jayita Bhattacharjee; Gunjan Verma; V K Aswal; P A Hassan


    Self-assembling behaviour of block copolymers and their ability to evade the immune system through polyethylene oxide stealth makes it an attractive candidate for drug encapsulation. Micelles formed by polyethylene oxide–polypropylene oxide–polyethylene oxide triblock copolymers (PEO–PPO–PEO), pluronic P123, have been employed for encapsulating the anti-cancer drug doxorubicin hydrochloride. The binding affinity of doxorubicin within the micelle carrier is enhanced through complex formation of drug and anionic surfactant, aerosol OT (AOT). Electrostatic binding of doxorubicin with negatively charged surfactants leads to the formation of hydrophobic drug–surfactant complexes. Surfactant-induced partitioning of the anti-cancer drug into nonpolar solvents such as chloroform is investigated. SANS measurements were performed on pluronic P123 mi-celles in the presence of drug–surfactant complex. No significant changes in the structure of the micelles are observed upon drug encapsulation. This demonstrates that surfactant–drug complexes can be encapsulated in block copolymer micelles without disrupting the structure of aggregates.

  17. Stable Polymer Micelles Formed by Metal Coordination

    Wang, Junyou; Stuart, Martien A. Cohen; Marcelis, Antonius T. M.; Colomb-Delsuc, Mathieu; Otto, Sijbren; van der Gucht, Jasper


    Metal-containing polymer micelles have attracted much attention due to their potential for medical and nanotechnological applications. In this paper, we present a method to prepare stable metal-containing polymer micelles. A diblock copolymer poly(4-vinylpyridine)-b-poly(ethylene oxide) (P4VP(48)-b-

  18. Synthesis of photolabile fluorescent polymeric micelles.

    Park, Teahoon; You, Jungmok; Oikawa, Hidetoshi; Kim, Eunkyoung


    A new amphiphilic block copolymers were synthesized with the atom transfer radical polymerization (ATRP) method. Then, the micelle structures were fabricated with a self-assembly method for application in nanocarriers and sensing. The fluorescent intensity was increased by a factor of 4 in the micelle solution due to more stacked pyrene moieties. The core-shell structure of the micelle was confirmed by HR-TEM images. The pyrene moieties were positioned in the core of the micelle, and the surface consisted of hydrophilic PMMA blocks. The ester bond of the polymer backbone was breakable by irradiation with UV light. Therefore, the micelle structure was deformed after UV irradiation, and the excimer peak was drastically reduced as the monomer peak appeared. The deformation of micelle structures was clearly confirmed by FE-SEM and NMR analysis. These photolabile polymeric micelles may be widely useful for photo-stimulative nanocarriers as well as for the design of new functional micelles with many other chromophores.

  19. Formation of micelles with complex coacervate cores.

    Cohen Stuart, M.A.; Besseling, N.A.M.; Fokkink, R.G.


    Micelles are commonly regarded as colloidal structures spontaneously formed by amphiphilic molecules, that is, molecules consisting of two distinct parts of which one is soluble and the other is insoluble. This definition is too restrictive: other kinds of molecules can also form micelles. We report

  20. Probing the causes of thermal hysteresis using tunable N agg micelles with linear and brush-like thermoresponsive coronas† †Electronic supplementary information (ESI) available: NMR spectra of small molecules and polymers, SEC chromatograms of the polymers, DLS, SLS and turbidimetry data for the micelles, a discussion of the chain density of micelles 11–15, additional calculations regarding the core composition of polymers 1–5 and definitions and calculations related to the light scattering data. See DOI: 10.1039/c6py01191h Click here for additional data file.

    Blackman, L. D.


    Self-assembled thermoresponsive polymers in aqueous solution have great potential as smart, switchable materials for use in biomedical applications. In recent years, attention has turned to the reversibility of these polymers’ thermal transitions, which has led to debate over what factors influence discrepancies in the transition temperature when heating the system compared to the temperature obtained when cooling the system, known as the thermal hysteresis. Herein, we synthesize micelles with tunable aggregation numbers (N agg) whose cores contain poly(n-butyl acrylate-co-N,N-dimethylacrylamide) (p(nBA-co-DMA)) and four different thermoresponsive corona blocks, namely poly(N-isopropylacrylamide) (pNIPAM), poly(N,N-diethylacrylamide) (pDEAm), poly(diethylene glycol monomethyl ether methacrylate) (pDEGMA) and poly(oligo(ethylene glycol) monomethyl ether methacrylate) (pOEGMA). By studying their thermoresponsive behavior, we elucidate the effects of changing numerous important characteristics both in the thermoresponsive chain chemistry and architecture, and in the structure of their self-assemblies. Our findings demonstrate large deviations in the reversibility between the self-assemblies and the corresponding thermoresponsive homopolymers; specifically we find that micelles whose corona consist of polymers with a brush-like architecture (pDEGMA and pOEGMA) exhibit irreversible phase transitions at a critical chain density. These results lead to a deeper understanding of stimuli-responsive self-assemblies and demonstrate the potential of tunable N agg micelles for uncovering structure–property relationships in responsive polymer systems. PMID:28496523

  1. Aggregation of phosphate and 1-tetradecyl-3-methylimidazolium chloride background electrolytes during micellar electrokinetic chromatography.

    Kazarjan, Jana; Vaher, Merike; Kaljurand, Mihkel


    We report the possible aggregation of phosphate and ionic liquid (1-tetradecyl-3-methylimidazolium chloride) based BGEs during MEKC. After a certain transit period, the aggregates appear as a random sequence of spikes on a UV detector signal. Root mean square values of the spikes and aggregation time (Ta ) were plotted against BGE concentrations. The observation suggests that MEKC is a simple and easy technique for micelle aggregation studies.

  2. Time-resolved small-angle neutron scattering of a micelle-to-vesicle transition

    Egelhaaf, S.U. [Institut Max von Laue - Paul Langevin (ILL), 38 -Grenoble (France); Schurtenberger, P. [Eidgenoessische Technische Hochschule, Zurich (Switzerland)


    Amphiphilic molecules spontaneously self-assemble in solution to form a variety of aggregates. Only limited information is available on the kinetics of the structural transitions as well as on the existence of non-equilibrium or metastable states. Aqueous mixtures of lecithin and bile salt are very interesting biological model-systems which exhibit a spontaneous transition from polymer-like mixed micelles to vesicles upon dilution. The small-angle neutron scattering (SANS) instrument D22, with its very high neutron flux and the broad range of scattering vectors covered in a single instrumental setting, allowed us for the first time to perform time-resolved scattering experiments in order to study the micelle-to-vesicle transition. The temporal evolution of the aggregate structures were followed and detailed information was obtained even on molecular length-scales. (author). 5 refs.

  3. Modeling and simulation of aggregation of membrane protein LAT with molecular variability in the number of binding sites for cytosolic Grb2-SOS1-Grb2.

    Ambarish Nag

    Full Text Available The linker for activation of T cells (LAT, the linker for activation of B cells (LAB, and the linker for activation of X cells (LAX form a family of transmembrane adaptor proteins widely expressed in lymphocytes. These scaffolding proteins have multiple binding motifs that, when phosphorylated, bind the SH2 domain of the cytosolic adaptor Grb2. Thus, the valence of LAT, LAB and LAX for Grb2 is variable, depending on the strength of receptor activation that initiates phosphorylation. During signaling, the LAT population will exhibit a time-varying distribution of Grb2 valences from zero to three. In the cytosol, Grb2 forms 1:1 and 2:1 complexes with the guanine nucleotide exchange factor SOS1. The 2:1 complex can bridge two LAT molecules when each Grb2, through their SH2 domains, binds to a phosphorylated site on a separate LAT. In T cells and mast cells, after receptor engagement, receptor phosphoyrlation is rapidly followed by LAT phosphorylation and aggregation. In mast cells, aggregates containing more than one hundred LAT molecules have been detected. Previously we considered a homogeneous population of trivalent LAT molecules and showed that for a range of Grb2, SOS1 and LAT concentrations, an equilibrium theory for LAT aggregation predicts the formation of a gel-like phase comprising a very large aggregate (superaggregate. We now extend this theory to investigate the effects of a distribution of Grb2 valence in the LAT population on the formation of LAT aggregates and superaggregate and use stochastic simulations to calculate the fraction of the total LAT population in the superaggregate.

  4. Multifunctional polymeric micelles for delivery of drugs and siRNA

    Aditi M. Jhaveri


    Full Text Available Polymeric micelles, self-assembling nano-constructs of amphiphilic copolymers with a core-shell structure have been used as versatile carriers for delivery of drugs as well as nucleic acids. They have gained immense popularity owing to a host of favorable properties including their capacity to effectively solubilize a variety of poorly soluble pharmaceutical agents, biocompatibility, longevity, high stability in vitro and in vivo and the ability to accumulate in pathological areas with compromised vasculature. Moreover, additional functions can be imparted to these micelles by engineering their surface with various ligands and cell-penetrating moieties to allow for specific targeting and intracellular accumulation, respectively, to load them with contrast agents to confer imaging capabilities, and incorporating stimuli-sensitive groups that allow drug release in response to small changes in the environment. Recently, there has been an increasing trend towards designing polymeric micelles which integrate a number of the above functions into a single carrier to give rise to smart, multifunctional polymeric micelles. Such multifunctional micelles can be envisaged as key to improving the efficacy of current treatments which have seen a steady increase not only in hydrophobic small molecules, but also in biologics including therapeutic genes, antibodies and small interfering RNA (siRNA. The purpose of this review is to highlight recent advances in the development of multifunctional polymeric micelles specifically for delivery of drugs and siRNA. In spite of the tremendous potential of siRNA, its translation into clinics has been a significant challenge because of physiological barriers to its effective delivery and the lack of safe, effective and clinically suitable vehicles. To that end, we also discuss the potential and suitability of multifunctional polymeric micelles, including lipid-based micelles, as promising vehicles for both siRNA and drugs.

  5. Chemical reactions in reverse micelle systems

    Matson, Dean W.; Fulton, John L.; Smith, Richard D.; Consani, Keith A.


    This invention is directed to conducting chemical reactions in reverse micelle or microemulsion systems comprising a substantially discontinuous phase including a polar fluid, typically an aqueous fluid, and a microemulsion promoter, typically a surfactant, for facilitating the formation of reverse micelles in the system. The system further includes a substantially continuous phase including a non-polar or low-polarity fluid material which is a gas under standard temperature and pressure and has a critical density, and which is generally a water-insoluble fluid in a near critical or supercritical state. Thus, the microemulsion system is maintained at a pressure and temperature such that the density of the non-polar or low-polarity fluid exceeds the critical density thereof. The method of carrying out chemical reactions generally comprises forming a first reverse micelle system including an aqueous fluid including reverse micelles in a water-insoluble fluid in the supercritical state. Then, a first reactant is introduced into the first reverse micelle system, and a chemical reaction is carried out with the first reactant to form a reaction product. In general, the first reactant can be incorporated into, and the product formed in, the reverse micelles. A second reactant can also be incorporated in the first reverse micelle system which is capable of reacting with the first reactant to form a product.




    Catalysis of organic reactions by unfunctionalized surfactant aggregates (micelles, vesicles) in aqueous solution is largely determined by medium effects induced at the micellar binding sites and by entropy effects due to compartimentalization. The efficiency of these catalytic effects responds to c

  7. Unimolecular micelles and electrostatic nanoassemblies stemming from hyperbranched polyethyleneimine

    Picco, A.; Azzaroni, O.; Ceolin, M. [Instituto de Investigaciones Fisicoquimicas Teoricas y Aplic, La Plata, BA (Argentina); Silbestri, G.F. [Universidad Nacional del Sur, Bahia Blanca Bueno (Argentina)


    Full text: Hyperbranched polyethyleneimine (HPEI) was used as a building block to construct different self-assembled soft nanomaterials. This was accomplished via covalent linkage of carboxylic acids (CA) of different chain lengths to terminal amino groups of HPEI, thus leading to the formation of reverse unimolecular micelles constituted of a hydrophilic core and a hydrophobic shell. On the other hand, acid base interactions in organic solvents between CAs and peripheral amino groups of HPEI also facilitated the formation of electrostatic assemblies with reverse micellar properties. In this work we describe the formation of both structures as well as their characterization using diverse techniques including SAXS, NMR, IR, and fluorescence spectroscopy, among others. Unimolecular micelles were synthesized through the reaction of HPEI (Mn= 10 KDa) and acyl chlorides with different chain lengths (C8, C10, C12, C14, C16, C18). Depending on the chain length, the solvent and the temperature, a broad variety of supra macromolecular assemblies can be observed by SAXS measurements, including structured aggregation, and gelation. Hyperbranched electrostatic assemblies were simply produced by mixing HPEI with selected carboxylic acids (C8, C10, C12, C14, C16, C18) in an appropriate solvent, which dissolves the CA, or both reactants, i.e. chloroform, toluene or THF. The formation of the assemblies was corroborated using FT-IR by monitoring the appearance of the carboxylate bands. SAXS experiments of electrostatically assembled micelles showed globular, core-shell structures, whose characteristics are similar, in many cases, to their covalent counterparts prepared using the same chain length CA shells. (author)

  8. Nano-cage-mediated refolding of insulin by PEG-PE micelle.

    Fang, Xiaocui; Yang, Tao; Wang, Luoyang; Yu, Jibing; Wei, Xiuli; Zhou, Yinjian; Wang, Chen; Liang, Wei


    Insulin aggregation has pronounced pharmaceutical implications and biological importance. Deposition of insulin aggregates is associated with type II diabetes and instability of pharmaceutical formulations. We present in this study the renaturation effect of PEG-PE micelle on dithiothreitol (DTT)-denatured insulin revealed by techniques including turbidity assay, circular dichroism (CD), thioflavinT (ThT) binding assay, bis-ANS binding assay, agarose gel electrophoresis and MALDI-TOF MS. The obtained results show that PEG-PE micelle having a hydrophilic nano-cage-like structure in which with a negative charge layer, can capture DTT-induced insulin A and B chains, and block their hydrophobic interaction, thereby preventing aggregation. The reduced insulin A and B chain in the nano-cage are capable of recognizing each other and form the native insulin with yields of ∼30% as measured by hypoglycemic activity analysis in mice. The observed insulin refolding assisted by PEG-PE micelle may be applicable to other proteins.

  9. Electrochemical and Microstructural Studies in Reinforced Mortar, Modified with Core-Shell Micelles

    Koleva, D. A.; Breugel, K. van; Boshkov, N.; Mol, J.M.C.; Wit, J.H.W. de


    This work reports on monitoring chloride-induced corrosion in reinforced mortar specimens, with and without addition of polymeric nano-aggregates in the mortar mixture. The investigation is a novel approach to control steel corrosion in reinforced concrete, hereby reporting the preliminary results, related to one of the main objectives: studying the influence of admixed polymer nano-aggregates (in the form of PEO113-b-PS218 core-shell micelles with a very low concentration of 0.006 wt.% per m...

  10. Micelle Catalysis of an Aromatic Substitution Reaction

    Corsaro, Gerald; Smith J. K.


    Describes an experiment in which the iodonation of aniline reaction is shown to undergo catalysis in solution of sodium lauryl sulfate which forms micelles with negatively charged pseudo surfaces. (MLH)

  11. Polysaccharide-Based Micelles for Drug Delivery

    Nan Zhang


    Full Text Available Delivery of hydrophobic molecules and proteins has been an issue due to poor bioavailability following administration. Thus, micelle carrier systems are being investigated to improve drug solubility and stability. Due to problems with toxicity and immunogenicity, natural polysaccharides are being explored as substitutes for synthetic polymers in the development of new micelle systems. By grafting hydrophobic moieties to the polysaccharide backbone, self-assembled micelles can be readily formed in aqueous solution. Many polysaccharides also possess inherent bioactivity that can facilitate mucoadhesion, enhanced targeting of specific tissues, and a reduction in the inflammatory response. Furthermore, the hydrophilic nature of some polysaccharides can be exploited to enhance circulatory stability. This review will highlight the advantages of polysaccharide use in the development of drug delivery systems and will provide an overview of the polysaccharide-based micelles that have been developed to date.

  12. Multiple criteria group decision making method based on binary connection number aggregation operators%基于二元联系数集结算子的多准则群决策方法

    汪新凡; 王坚强; 杨恶恶


    定义了二元联系数的加性运算法则,给出了几种新的算术集结算子,即二元联系数加权算术平均(BCNWAA)算子、二元联系数有序加权平均(BCNOWA)算子和二元联系数混合集结(BCNHA)算子,提出了一种基于二元联系数的准则权重信息不完全确定的群决策方法。该方法利用BCNWAA算子和BCNHA算子对二元联系数准则值进行集结;利用二元联系数准则值的方差和准则权重的随机性,通过构建优化模型确定最优准则权重。最后,通过实例分析表明了该方法的可行性和有效性。%Some additive operational laws of binary connection numbers are defined, and several new arithmetic aggregation operators, such as the binary connection number weighted arithmetic averaging(BCNWAA) operator, the binary connection number ordered weighted averaging(BCNOWA) operator and the binary connection number hybrid aggregation(BCNHA) operator, are proposed. Then an approach is developed for solving multiple criterion group decision making based on binary connection numbers with incomplete uncertain information. In this method, binary connection number criterion values are aggregated using the BCNWAA operator and the BCNHA operator, some optimal models are constructed to determine the optimal criterion weights using the variance of binary connection number criterion values and the randomness of criterion weights. Finally, an example is given to illustrate the feasibility and effectiveness of the developed method.

  13. Casein Micelle Dispersions under Osmotic Stress

    Bouchoux, Antoine; Cayemitte, Pierre-Emerson; Jardin, Julien; Gésan-Guiziou, Geneviève; Cabane, Bernard


    Casein micelles dispersions have been concentrated and equilibrated at different osmotic pressures using equilibrium dialysis. This technique measured an equation of state of the dispersions over a wide range of pressures and concentrations and at different ionic strengths. Three regimes were found. i), A dilute regime in which the osmotic pressure is proportional to the casein concentration. In this regime, the casein micelles are well separated and rarely interact, whereas the osmotic press...

  14. Preparation of ZrO2 nano-particles by the hydrolysis of ZrOCl2 solution in the reverse micelles

    Chensha Li; Tongxiang Liang; Tianyong Luo


    Zirconia nano-particles have been produced by the hydrolysis of ZrOGl2 solution in the reverse micelles of a liquid-liquid two-phase system, in which sodium bis(2-ethylhexyl) sulfosuccinite (AOT) and toluene were chosen as the surfactant and organic phase, respectively. The reverse micelles prevented the aggregation of primary particles and reduced the diameters of zirconia nanoparticles. Superfine zirconia powders soft-aggregated by the zirconia nano-particles were obtained. The diameters of zirconia nanoparticles were influenced by the quantity of the surfactant.

  15. Polymeric micelles for acyclovir drug delivery.

    Sawdon, Alicia J; Peng, Ching-An


    Polymeric prodrug micelles for delivery of acyclovir (ACV) were synthesized. First, ACV was used directly to initiate ring-opening polymerization of ɛ-caprolactone to form ACV-polycaprolactone (ACV-PCL). Through conjugation of hydrophobic ACV-PCL with hydrophilic methoxy poly(ethylene glycol) (MPEG) or chitosan, polymeric micelles for drug delivery were formed. (1)H NMR, FTIR, and gel permeation chromatography were employed to show successful conjugation of MPEG or chitosan to hydrophobic ACV-PCL. Through dynamic light scattering, zeta potential analysis, transmission electron microscopy, and critical micelle concentration (CMC), the synthesized ACV-tagged polymeric micelles were characterized. It was found that the average size of the polymeric micelles was under 200nm and the CMCs of ACV-PCL-MPEG and ACV-PCL-chitosan were 2.0mgL(-1) and 6.6mgL(-1), respectively. The drug release kinetics of ACV was investigated and cytotoxicity assay demonstrates that ACV-tagged polymeric micelles were non-toxic.

  16. Nonionic reverse micelles near the critical point.

    Shrestha, Lok Kumar; Shrestha, Rekha Goswami


    We report shape, size, and internal cross-sectional structure of diglycerol monomyristate (C₁₄G₂) reverse micelles in n-hexadecane near the critical point using small-angle X-ray scattering (SAXS). Pair-distance distribution function, p(r), which gives structural information in real-space, was obtained by indirect Fourier transformation (IFT) method. The p(r) showed a clear picture of rodlike micelles at higher temperatures well above the critical point (micellar solution phase separates into two immiscible liquids at ~ 48°C). At a fixed surfactant concentration (5% C₁₄G₂), decrease in temperature increases the micellar size monotonously and surprisingly shape of the p(r) curve at 50°C; close to the critical point, mimics the shape of the two dimensional disk-like micelles indicating the onset of critical fluctuations (attractive interactions among rodlike micelles forming a weak network). A similar behavior has been observed with normal micelles in aqueous system near the critical point. When the system is heated to 60°C, shape of the p(r) curve regains rodlike structure. At fixed temperature of 60°C, increase in C₁₄G₂ concentration induced one dimensional micellar growth. Maximum length of micelles increases from ca. 23.5 to 46.0 nm upon increasing concentration from 1 to 12% keeping cross section diameter apparently unchanged at ca. 4.0 nm.

  17. Marine Synechococcus Aggregation

    Neuer, S.; Deng, W.; Cruz, B. N.; Monks, L.


    Cyanobacteria are considered to play an important role in the oceanic biological carbon pump, especially in oligotrophic regions. But as single cells are too small to sink, their carbon export has to be mediated by aggregate formation and possible consumption by zooplankton producing sinking fecal pellets. Here we report results on the aggregation of the ubiquitous marine pico-cyanobacterium Synechococcus as a model organism. We first investigated the mechanism behind such aggregation by studying the potential role of transparent exopolymeric particles (TEP) and the effects of nutrient (nitrogen or phosphorus) limitation on the TEP production and aggregate formation of these pico-cyanobacteria. We further studied the aggregation and subsequent settling in roller tanks and investigated the effects of the clays kaolinite and bentonite in a series of concentrations. Our results show that despite of the lowered growth rates, Synechococcus in nutrient limited cultures had larger cell-normalized TEP production, formed a greater volume of aggregates, and resulted in higher settling velocities compared to results from replete cultures. In addition, we found that despite their small size and lack of natural ballasting minerals, Synechococcus cells could still form aggregates and sink at measureable velocities in seawater. Clay minerals increased the number and reduced the size of aggregates, and their ballasting effects increased the sinking velocity and carbon export potential of aggregates. In comparison with the Synechococcus, we will also present results of the aggregation of the pico-cyanobacterium Prochlorococcus in roller tanks. These results contribute to our understanding in the physiology of marine Synechococcus as well as their role in the ecology and biogeochemistry in oligotrophic oceans.

  18. Structure and dynamics of the conserved protein GPI anchor core inserted into detergent micelles.

    Chevalier, Franck; Lopez-Prados, Javier; Groves, Patrick; Perez, Serge; Martín-Lomas, Manuel; Nieto, Pedro M


    A suitable approach which combines nuclear magnetic resonance (NMR) spectroscopy and molecular dynamics (MD) simulations have been used to study the structure and the dynamics of the glycosylphosphatidylinositol (GPI) anchor Manalphal-2Manalpha1-6Manalphal -4GlcNalpha1-6myo-inositol-1-OPO(3)-sn-1,2-dimyristoylglycerol (1) incorporated into dodecylphosphatidylcholine (DPC) micelles. The results have been compared to those previously obtained for the products obtainable from (1) after phospholipase cleavage, in aqueous solution. Relaxation and diffusion NMR experiments were used to establish the formation of stable aggregates and the insertion of (1) into the micelles. MD calculations were performed including explicit water, sodium and chloride ions and using the Particle Mesh Ewald approach for the evaluation of the electrostatic energy term. The MD predicted three dimensional structure and dynamics were substantiated by nuclear overhauser effect (NOE) measurements and relaxation data. The pseudopentasaccharide structure, which was not affected by incorporation of (1) into the micelle, showed a complex dynamic behaviour with a faster relative motion at the terminal mannopyranose unit and decreased mobility close to the micelle. This motion may be better described as an oscillation relative to the membrane rather than a folding event.

  19. The pressure-induced, lactose-dependent changes in the composition and size of casein micelles.

    Wang, Pengjie; Jin, Shaoming; Guo, Huiyuan; Zhao, Liang; Ren, Fazheng


    The effects of lactose on the changes in the composition and size of casein micelles induced by high-pressure treatment and the related mechanism of action were investigated. Dispersions of ultracentrifuged casein micelle pellets with 0-10% (w/v) lactose were subjected to high pressure (400 MPa) at 20 °C for 40 min. The results indicated that the level of non-sedimentable caseins was positively related to the amount of lactose added prior to pressure treatment, and negatively correlated to the size. A mechanism for the pressure-induced, lactose-dependent changes in the casein micelles is proposed. Lactose inhibits the hydrophobic interactions between the micellar fragments during or after pressure release, through the hydrophilic layer formed by their hydrogen bonds around the micellar fragments. In addition, lactose does not favour the association between calcium and the casein aggregates after pressure release. Due to these two functions, lactose inhibited the formation of larger micelles after pressure treatment.

  20. Ultrasound effects on the assembly of casein micelles in reconstituted skim milk.

    Liu, Zheng; Juliano, Pablo; Williams, Roderick P W; Niere, Julie; Augustin, Mary Ann


    Reconstituted skim milks (10 % w/w total solids, pH 6·7-8·0) were ultrasonicated (20, 400 or 1600 kHz at a specific energy input of 286 kJ/kg) at a bulk milk temperature of <30 °C. Application of ultrasound to milk at different pH altered the assembly of the casein micelle in milk, with greater effects at higher pH and lower frequency. Low frequency ultrasound caused greater disruption of casein micelles causing release of protein from the micellar to the serum phase than high frequency. The released protein re-associated to form aggregates of smaller size but with surface charge similar to the casein micelles in the original milk. Ultrasound may be used as a physical intervention to alter the size of the micelles and the partitioning of caseins between the micellar and serum phases in milk. The altered protein equilibria induced by ultrasound treatment may have potential for the development of milk with novel functionality.

  1. Specific interactions within micelle microenvironment in different charged dye/surfa

    Adina Roxana Petcu


    Full Text Available The interactions of two ionic dyes, Crystal Violet and Methyl Orange, with different charged surfactants and also with a nonionic surfactant were investigated using surface tension measurements and visible spectroscopy in pre-micellar and post-micellar regions. It was found that for the water dominant phase systems the dye was localized between the polar heads, at the exterior of the direct micelle shells for all the systems. For the oil dominant phase systems, in case of the same charged dye/surfactant couples, the dye was localized in the micelle shell between the hydrocarbon chain of the surfactant nearby the hydrophilic head groups while for nonionic surfactant and oppositely charged dye/surfactant, localization of dye was between the oxyethylenic head groups towards the interior of the micelle core. Mixed aggregates of the dye and surfactant (below the critical micellar concentration of cationic surfactant, dye-surfactant ion pair and surfactant-micelles were present. The values of equilibrium constants (for TX-114/MO and TX-114/CV systems were 0.97 and 0.98, respectively, partition coefficients between the micellar and bulk water phases and standard free energy (for the nonionic systems were −12.59 kJ/mol for MO and −10.97 kJ/mol for CV were calculated for all the studied systems. The partition processes were exothermic and occurred spontaneously.

  2. Fabrication and characterization of nuclear localization signal-conjugated glycol chitosan micelles for improving the nuclear delivery of doxorubicin

    Zhao J


    Full Text Available Jingmou Yu,1 Xin Xie,1 Meirong Zheng,1 Ling Yu,2 Lei Zhang,1 Jianguo Zhao,1 Dengzhao Jiang,1 Xiangxin Che11Key Laboratory of Systems Biology Medicine of Jiangxi Province, College of Basic Medical Science, Jiujiang University, Jiujiang, 2Division of Nursing, 2nd Affiliated Hospital, Yichun University, Yichun, People's Republic of ChinaBackground: Supramolecular micelles as drug-delivery vehicles are generally unable to enter the nucleus of nondividing cells. In the work reported here, nuclear localization signal (NLS-modified polymeric micelles were studied with the aim of improving nuclear drug delivery.Methods: In this research, cholesterol-modified glycol chitosan (CHGC was synthesized. NLS-conjugated CHGC (NCHGC was synthesized and characterized using proton nuclear magnetic resonance spectroscopy, dynamic light scattering, and fluorescence spectroscopy. Doxorubicin (DOX, an anticancer drug with an intracellular site of action in the nucleus, was chosen as a model drug. DOX-loaded micelles were prepared by an emulsion/solvent evaporation method. The cellular uptake of different DOX formulations was analyzed by flow cytometry and confocal laser scanning microscopy. The cytotoxicity of blank micelles, free DOX, and DOX-loaded micelles in vitro was investigated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay in HeLa and HepG2 cells.Results: The degree of substitution was 5.9 cholesterol and 3.8 NLS groups per 100 sugar residues of the NCHGC conjugate. The critical aggregation concentration of the NCHGC micelles in aqueous solution was 0.0209 mg/mL. The DOX-loaded NCHGC (DNCHGC micelles were observed as being almost spherical in shape under transmission electron microscopy, and the size was determined as 248 nm by dynamic light scattering. The DOX-loading content of the DNCHGC micelles was 10.1%. The DOX-loaded micelles showed slow drug-release behavior within 72 hours in vitro. The DNCHGC micelles exhibited greater

  3. 基于改进区间数密度集结算子指标群赋权方法%Research on Obtaining the Weights of Index Group Based on Modified Interval Number Density Aggregation Operator



    A decision-making method with a modified interval number density aggregation operator is proposed to solve the group weights problems with index data known and weights unknown .First, the several concepts of in-terval number and interval number density aggregation operator are introduced , the method of interval number clustering is improved , the direct algorithm is applied to cluster the one-dimensional data , and fuzzy statistics variables are defined to make sure which is the best way to clustering .Then based on a modified interval number density aggregation operator the group weights problems with index data known and weights unknown are solved . Finally it is shown that the method is feasible and effective with an example .%针对指标数据已知,而权重数据未知的群组赋权问题,给出了一种基于改进的区间数密度集结算子来进行指标群组赋权的决策方法。首先给出了区间数和区间数密度集结算子( IDM)的定义及性质,改进了以前区间数聚类的方法,应用直接法对一维区间数据组进行聚类,并定义了模糊统计量,以确定最为合理的一种聚类方式。然后基于改进的区间数密度集结算子这种数学模型,来解决指标值数据已知,而权重未知的群组赋权问题。最后举例说明该方法的可行性和实用性。

  4. Cytotoxicity Study on Luminescent Nanocrystals Containing Phospholipid Micelles in Primary Cultures of Rat Astrocytes

    Valente, Gianpiero; Fanizza, Elisabetta; Laquintana, Valentino; Denora, Nunzio; Fasano, Anna; Striccoli, Marinella; Colella, Matilde; Agostiano, Angela; Curri, M. Lucia; Liuzzi, Grazia Maria


    Luminescent colloidal nanocrystals (NCs) are emerging as a new tool in neuroscience field, representing superior optical probes for cellular imaging and medical diagnosis of neurological disorders with respect to organic fluorophores. However, only a limited number of studies have, so far, explored NC applications in primary neurons, glia and related cells. Indeed astrocytes, as resident cells in the central nervous system (CNS), play an important pathogenic role in several neurodegenerative and neuroinflammatory diseases, therefore enhanced imaging tools for their thorough investigation are strongly amenable. Here, a comprehensive and systematic study on the in vitro toxicological effect of core-shell type luminescent CdSe@ZnS NCs incorporated in polyethylene glycol (PEG) terminated phospholipid micelles on primary cultures of rat astrocytes was carried out. Cytotoxicity response of empty micelles based on PEG modified phospholipids was compared to that of their NC containing counterpart, in order to investigate the effect on cell viability of both inorganic NCs and micelles protecting NC surface. Furthermore, since the surface charge and chemistry influence cell interaction and toxicity, effect of two different functional groups terminating PEG-modified phospholipid micelles, namely amine and carboxyl group, respectively, was evaluated against bare micelles, showing that carboxyl group was less toxic. The ability of PEG-lipid micelles to be internalized into the cells was qualitatively and quantitatively assessed by fluorescence microscopy and photoluminescence (PL) assay. The results of the experiments clearly demonstrate that, once incorporated into the micelles, a low, not toxic, concentration of NCs is sufficient to be distinctly detected within cells. The overall study provides essential indications to define the optimal experimental conditions to effectively and profitably use the proposed luminescent colloidal NCs as optical probe for future in vivo

  5. Structure formation of lipid membranes: Membrane self-assembly and vesicle opening-up to octopus-like micelles

    Noguchi, Hiroshi


    We briefly review our recent studies on self-assembly and vesicle rupture of lipid membranes using coarse-grained molecular simulations. For single component membranes, lipid molecules self-assemble from random gas states to vesicles via disk-shaped clusters. Clusters aggregate into larger clusters, and subsequently the large disks close into vesicles. The size of vesicles are determined by kinetics than by thermodynamics. When a vesicle composed of lipid and detergent types of molecules is ruptured, a disk-shaped micelle called bicelle can be formed. When both surfactants have negligibly low critical micelle concentration, it is found that bicelles connected with worm-like micelles are also formed depending on the surfactant ratio and spontaneous curvature of the membrane monolayer.

  6. Propagation of Tau aggregates.

    Goedert, Michel; Spillantini, Maria Grazia


    Since 2009, evidence has accumulated to suggest that Tau aggregates form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of Tau aggregates is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighbouring cells. In mice, the intracerebral injection of Tau inclusions induced the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Short fibrils constituted the major species of seed-competent Tau. The existence of several human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.

  7. Solubilization of Phenol Derivatives in Polymer Micelles Formed by Cationic Block Copolymer

    Irma Fuentes


    Full Text Available The aggregation of cationic block copolymers formed by polystyrene (PS and poly(ethyl-4-vinylpyridine (PS-b-PE4VP was studied in aqueous solution. Diblock copolymers of PS and poly(4-vinylpyridine were synthesized by sequential anionic polymerization using BuLi as initiator. Subsequently, the 4-vinylpyridine units were quaternized with ethyl bromide to obtain cationic PS-b-PE4VP block copolymers with different quaternization degree. The self-aggregation of cationic block copolymers was studied by fluorescence probing, whereas the morphology and size of polymer micelles were determined by transmission electronic microscopy. Results indicate that spherical micelles with sizes lower than 100 nm were formed, whereas their micropolarity decreases with increasing quaternization degree. The partition of phenols between the micellar and aqueous phase was studied by using the pseudo-phase model, and the results show that the partition coefficients increase with increasing length of the side alkyl chain and are larger for star micelles. These results are discussed in terms of three-region model.

  8. Synthesis and characterization of Fe colloid catalysts in inverse micelle solutions

    Martino, A.; Stoker, M.; Hicks, M. [Sandia National Lab., Alburquerque, NM (United States)] [and others


    Surfactant molecules, possessing a hydrophilic head group and a hydrophobic tail group, aggregate in various solvents to form structured solutions. In two component mixtures of surfactant and organic solvents (e.g., toluene and alkanes), surfactants aggregate to form inverse micelles. Here, the hydrophilic head groups shield themselves by forming a polar core, and the hydrophobic tails groups are free to move about in the surrounding oleic phase. The formation of Fe clusters in inverse miscelles was studied.Iron salts are solubilized within the polar interior of inverse micelles, and the addition of the reducing agent LiBH{sub 4} initiates a chemical reduction to produce monodisperse, nanometer sized Fe based particles. The reaction sequence is sustained by material exchange between inverse micelles. The surfactant interface provides a spatial constraint on the reaction volume, and reactions carried out in these micro-heterogeneous solutions produce colloidal sized particles (10-100{Angstrom}) stabilized in solution against flocculation of surfactant. The clusters were stabilized with respect to size with transmission electron microscopy (TEM) and with respect to chemical composition with Mossbauer spectroscopy, electron diffraction, and x-ray photoelectron spectroscopy (XPS). In addition, these iron based clusters were tested for catalytic activity in a model hydrogenolysis reaction. The hydrogenolysis of naphthyl bibenzyl methane was used as a model for coal pyrolysis.

  9. Lipoamino acid-based micelles as promising delivery vehicles for monomeric amphotericin B.

    Serafim, Cláudia; Ferreira, Inês; Rijo, Patrícia; Pinheiro, Lídia; Faustino, Célia; Calado, António; Garcia-Rio, Luis


    Lipoamino acid-based micelles have been developed as delivery vehicles for the hydrophobic drug amphotericin B (AmB). The micellar solubilisation of AmB by a gemini lipoamino acid (LAA) derived from cysteine and its equimolar mixtures with the bile salts sodium cholate (NaC) and sodium deoxycholate (NaDC), as well as the aggregation sate of the drug in the micellar systems, was studied under biomimetic conditions (phosphate buffered-saline, pH 7.4) using UV-vis spectroscopy. Pure surfactant systems and equimolar mixtures were characterized by tensiometry and important parameters were determined, such as critical micelle concentration (CMC), surface tension at the CMC (γCMC), maximum surface excess concentration (Γmax), and minimum area occupied per molecule at the water/air interface (Amin). Rheological behaviour from viscosity measurements at different shear rates was also addressed. Solubilisation capacity was quantified in terms of molar solubilisation ratio (χ), micelle-water partition coefficient (KM) and Gibbs energy of solubilisation (ΔGs°). Formulations of AmB in micellar media were compared in terms of drug loading, encapsulation efficiency, aggregation state of AmB and in vitro antifungal activity against Candida albicans. The LAA-containing micellar systems solubilise AmB in its monomeric and less toxic form and exhibit in vitro antifungal activity comparable to that of the commercial formulation Fungizone.

  10. Molecular Exchange in Ordered Diblock Copolymer Micelles

    Choi, Soo-Hyung; Lodge, Timothy; Bates, Frank


    Previously, molecular exchange between spherical micelles in dilute solution (1 vol% polymer) was investigated using time-resolved small-angle neutron scattering (TR-SANS). As the concentration of spherical micelles formed by the diblock copolymers increases, the micelles begin to overlap and eventually pack onto body-centered cubic (BCC) lattice. In this study, concentrated, ordered micelles (15 vol% polymers) prepared by dispersing isotopically labeled poly(styrene- b -ethylene-alt-propylene) in an isotopic squalane mixture was investigated to understand the micellar concentration dependence of the molecular exchange. Perfectly random mixing of isotopically labeled micelles on the BCC lattice was confirmed by SANS patterns where the interparticle contribution vanishes, resulting in an intensity that directly relates to the exchange kinetics. The measured molecular exchange process for the concentrated, ordered system is qualitatively consistent with the previous observations, but the rate is more than an order of magnitude slower than that for the dilute, disordered system. Infineum(IPrime), MRSEC(NSF), NIST.

  11. Antisense precision polymer micelles require less poly(ethylenimine) for efficient gene knockdown

    Fakhoury, Johans J.; Edwardson, Thomas G.; Conway, Justin W.; Trinh, Tuan; Khan, Farhad; Barłóg, Maciej; Bazzi, Hassan S.; Sleiman, Hanadi F.


    Therapeutic nucleic acids are powerful molecules for shutting down protein expression. However, their cellular uptake is poor and requires transport vectors, such as cationic polymers. Of these, poly(ethylenimine) (PEI) has been shown to be an efficient vehicle for nucleic acid transport into cells. However, cytotoxicity has been a major hurdle in the development of PEI-DNA complexes as clinically viable therapeutics. We have synthesized antisense-polymer conjugates, where the polymeric block is completely monodisperse and sequence-controlled. Depending on the polymer sequence, these can self-assemble to produce micelles of very low polydispersity. The introduction of linear poly(ethylenimine) to these micelles leads to aggregation into size-defined PEI-mediated superstructures. Subsequently, both cellular uptake and gene silencing are greatly enhanced over extended periods compared to antisense alone, while at the same time cellular cytotoxicity remains very low. In contrast, gene silencing is not enhanced with antisense polymer conjugates that are not able to self-assemble into micelles. Thus, using antisense precision micelles, we are able to achieve significant transfection and knockdown with minimal cytotoxicity at much lower concentrations of linear PEI then previously reported. Consequently, a conceptual solution to the problem of antisense or siRNA delivery is to self-assemble these molecules into `gene-like' micelles with high local charge and increased stability, thus reducing the amount of transfection agent needed for effective gene silencing.Therapeutic nucleic acids are powerful molecules for shutting down protein expression. However, their cellular uptake is poor and requires transport vectors, such as cationic polymers. Of these, poly(ethylenimine) (PEI) has been shown to be an efficient vehicle for nucleic acid transport into cells. However, cytotoxicity has been a major hurdle in the development of PEI-DNA complexes as clinically viable


    M. S. Santos

    Full Text Available Abstract Surfactants are amphiphilic molecules that can spontaneously self-assemble in solution, forming structures known as micelles. Variations in temperature, pH, and electrolyte concentration imply changes in the interactions between surfactants and micelle stability conditions, including micelle size distribution and micelle shape. Here, molecular thermodynamics is used to describe and predict conditions of micelle formation in surfactant solutions by directly calculating the minimum Gibbs free energy of the system, corresponding to the most stable condition of the surfactant solution. In order to find it, the proposed methodology takes into account the micelle size distribution and two possible geometries (spherical and spherocylindrical. We propose a numerical optimization methodology where the minimum free energy can be reached faster and in a more reliable way. The proposed models predict the critical micelle concentration well when compared to experimental data, and also predict the effect of salt on micelle geometry transitions.

  13. Efficient deacylation of N-acylimidazoles by functionalized surfactant micelles

    Ihara, Yasuji; Nango, Mamoru; Koga, Joichi; ナンゴ, マモル; 南後, 守


    Hydroxylated surfactant micelles are powerful catalysts for the deacylation of N-acylimidazoles under neutral conditions; the deacylation rates of hydrophobia acylimidazoles are accelerated remarkably by functionalized micelles containing three hydroxy groups at the polar head.

  14. Modeling the Self-Assembly and Stability of DHPC Micelles Using Atomic Resolution and Coarse Grained MD Simulations.

    Kraft, Johan F; Vestergaard, Mikkel; Schiøtt, Birgit; Thøgersen, Lea


    Membrane mimics such as micelles and bicelles are widely used in experiments involving membrane proteins. With the aim of being able to carry out molecular dynamics simulations in environments comparable to experimental conditions, we set out to test the ability of both coarse grained and atomistic resolution force fields to model the experimentally observed behavior of the lipid 1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC), which is a widely used lipid for biophysical characterization of membrane proteins. It becomes clear from our results that a satisfactory modeling of DHPC aggregates in solution poses different demands to the force field than do the modeling of bilayers. First, the representation of the short tailed lipid DHPC in the coarse grained force field MARTINI is assessed with the intend of successfully self-assemble micelles with structural characteristics comparable to experimental data. Then, the use of the recently presented polarizable water model in MARTINI is shown to be essential for producing micelles that are structurally in accordance with experiments. For the atomistic representations of DHPC micelles in solution the GROMOS96 force field with lipid parameters by A. Kukol fails to maintain stable micelles, whereas the most recent CHARMM36 lipid parameters and GROMOS96 with the so-called Berger lipid parameters both succeed in this regard.

  15. Structure of modified [epsilon]-polylysine micelles and their application in improving cellular antioxidant activity of curcuminoids

    Yu, Hailong; Li, Ji; Shi, Ke; Huang, Qingrong (Rutgers)


    The micelle structure of octenyl succinic anhydride modified {var_epsilon}-polylysine (M-EPL), an anti-microbial surfactant prepared from natural peptide {var_epsilon}-polylysine in aqueous solution has been studied using synchrotron small-angle X-ray scattering (SAXS). Our results revealed that M-EPLs formed spherical micelles with individual size of 24-26 {angstrom} in aqueous solution which could further aggregate to form a larger dimension with averaged radius of 268-308 {angstrom}. Furthermore, M-EPL micelle was able to encapsulate curcuminoids, a group of poorly-soluble bioactive compounds from turmeric with poor oral bioavailability, and improve their water solubility. Three loading methods, including solvent evaporation, dialysis, and high-speed homogenization were compared. The results indicated that the dialysis method generated the highest loading capacity and curcuminoids water solubility. The micelle encapsulation was confirmed as there were no free curcuminoid crystals detected in the differential scanning calorimetry analysis. It was also demonstrated that M-EPL encapsulation stabilized curcuminoids against hydrolysis at pH 7.4 and the encapsulated curcuminoids showed elevated cellular antioxidant activity compared with free curcuminoids. This work suggested that M-EPL could be used as new biopolymer micelles for delivering poorly soluble drugs/phytochemicals and improving their bioactivities.

  16. New Insights into the Dynamics of Zwitterionic Micelles and Their Hydration Waters by Gigahertz-to-Terahertz Dielectric Spectroscopy

    George, Deepu K; Hull, Olivia A; Mishra, Archana; Capelluto, Daniel G S; Mitchell-Koch, Katie R; Vinh, Nguyen Q


    Gigahertz-to-terahertz spectroscopy of macromolecules in aqueous environments provides an important approach for identifying their global and transient molecular structures, as well as directly assessing hydrogen-bonding. We report dielectric properties of zwitterionic dodecylphosphocholine (DPC) micelles in aqueous solutions over a wide frequency range, from 50 MHz to 1.12 THz. The dielectric relaxation spectra reveal different polarization mechanisms at the molecular level, reflecting the complexity of DPC micelle-water interactions. We have made a deconvolution of the spectra into different components and combined them with the effective-medium approximation to separate delicate processes of micelles in water. Our measurements demonstrate reorientational motion of the DPC surfactant head groups within the micelles, and two levels of hydration water shells, including tightly- and loosely-bound hydration water layers. From the dielectric strength of bulk water in DPC solutions, we found that the number of wa...

  17. Exploring molecular insights into aggregation of hydrotrope sodium cumene sulfonate in aqueous solution: a molecular dynamics simulation study.

    Das, Shubhadip; Paul, Sandip


    Hydrotropes are an important class of molecules that enhance the solubility of an otherwise insoluble or sparingly soluble solute in water. Besides this, hydrotropes are also known to self-assemble in aqueous solution and form aggregates. It is the hydrotrope aggregate that helps in solubilizing a solute molecule in water. In view of this, we try to understand the underlying mechanism of self-aggregation of hydrotrope sodium cumene sulfonate (SCS) in water. We have carried out classical molecular dynamics simulations of aqueous SCS solutions with a regime of concentrations. Moreover, to examine the effect of temperature change on SCS aggregation, if any, we consider four different temperatures ranging from 298 to 358 K. From the estimation of densities of different solutions we calculate apparent and partial molal volumes of the hydrotrope. The changes in these quantities increase sharply at a characteristic minimum hydrotrope concentration. The determination of molal expansibility at infinite dilution for different temperatures indicates the water structure breaking by SCS molecules, which is further confirmed by the calculations of water-water pair correlation functions. In comparison with typical surfactants in micelles, a slightly lower value of volumetric change upon aggregation per carbon atom suggests the formation of a more closely packed structure of hydrotrope aggregates. A close examination of different structural properties of hydrotrope solutions reveals that the hydrophobic interactions through their hydrophobic tails significantly contribute in hydrotrope aggregation,and the dehydration of hydrophobic tail at elevated temperatures is also visible. Remarkably, the aggregates have little or no impact on the average number of water-SCS hydrogen bonds.

  18. Mechanism of Molecular Exchange in Copolymer Micelles

    Choi, Soo-Hyung; Lodge, Timothy; Bates, Frank


    Compared to thermodynamic structure, much less has been known about the kinetics of block copolymer micelles which should underlay the attainment of thermodynamic equilibrium. In this presentation, molecular exchange between spherical micelles formed by isotopically labeled diblock copolymers was investigated using time-resolved small-angle neutron scattering. Two pairs of structurally matched poly(styrene-b-ethylene-alt-propylene) (PS-PEP) were synthesized and dispersed in isotopic mixture of squalane, highly selective to PEP block. Each pair includes polymers with fully deuterated (dPS-PEP) and a normal (hPS-PEP) PS blocks. Temperature dependence of the micelle exchange rate R(t) is consistent with melt dynamics for the core polymer. Furthermore, R(t) is significantly sensitive to the core block length N due to the thermodynamic penalty associated with ejecting a core block into the solvent. This hypersensitivity, combined with modest polydispersity in N, leads to an approximately logarithmic decay in R(t).

  19. Coal desulfurization through reverse micelle biocatalysis process

    Lee, K.; Yen, T.F.


    A novel bioprocess using micelle biocatalysis has been attempted to minimize several disadvantages of conventional microbial coal desulfurization scale-up processes. The reverse micelle biocatalysis process consists of a water-immiscible organic medium, a surfactant, an aqueous phase and sulfur-oxidizing bacteria or enzymes. This process has been successful for removing sulfur from bituminous coal (Illinois coal 5). The preliminary results showed that coal desulfurization through the use of cell-free enzyme extracts of Thiobacillus ferrooxidans ATCC 19859 was better than that of bacteria itself. The use of enzymes has shown potential for commercial coal desulfurization process as well. This same process is being applied to the thermophillic bacteria Sulfolobus acidocaldarius ATCC 33909. The implications of these experimental results are discussed, including a hypothetical mechanism using reverse micelle biocatalytical process for coal desulfurization.

  20. Salt-induced release of lipase from polyelectrolyte complex micelles

    Lindhoud, Saskia; de Vries, Renko; Schweins, Ralf; Stuart, Martien A. Cohen; Norde, Willem


    With the aim to gain insight into the possible applicability of protein-filled polyelectrolyte complex micelles under physiological salt conditions, we studied the behavior of these micelles as a function of salt concentration. The micelles form by electrostatically driven co-assembly from strong ca

  1. Stability of casein micelles in milk

    Tuinier, R.; de Kruif, C. G.


    Casein micelles in milk are proteinaceous colloidal particles and are essential for the production of flocculated and gelled products such as yogurt, cheese, and ice-cream. The colloidal stability of casein micelles is described here by a calculation of the pair potential, containing the essential contributions of brush repulsion, electrostatic repulsion, and van der Waals attraction. The parameters required are taken from the literature. The results are expressed by the second osmotic virial coefficient and are quite consistent with experimental findings. It appears that the stability is mainly attributable to a steric layer of κ-casein, which can be described as a salted polyelectrolyte brush.

  2. Polymeric micelles as carriers of diagnostic agents.



    This review deals with diagnostic applications of polymeric micelles composed of amphiphilic block-copolymers. In aqueous solutions these polymers spontaneously form particles with diameter 20-100 nm. A variety of diagnostic moieties can be incorporated covalently or non-covalently into the particulates with high loads. Resulting particles can be used as particulate agents for diagnostic imaging using three major imaging modalities: gamma-scintigraphy, magnetic resonance imaging and computed tomography. The use of polyethyleneoxide-diacyllipid micelles loaded with chelated (111)In/Gd(3+) as well as iodine-containing amphiphilic copolymer in percutaneous lymphography and blood pool/liver imaging are discussed as specific examples.

  3. Structural investigations of sodium caseinate micelles in complex environments

    Huck Iriart, C.; Herrera, M.L.; Candal, R. [Universidad de Buenos Aires, Buenos Aires (Argentina); Oliveira, C.L.P. [Universidade de Sao Paulo (USP), Sao Paulo, SP (Brazil); Torriani, I. [Laboratorio Nacional de Luz Sincrotron (LNLS), Campinas, SP (Brazil)


    Full text: The most frequent destabilization mechanisms in Sodium Caseinate (NaCas) emulsions are creaming and flocculation. Coarse or fine emulsions with low protein con- tent destabilize mainly by creaming. If migration mechanism is suppressed, flocculation may become the main mechanism of destabilization. Small Angle X-Ray Scattering (SAXS) technique was applied to investigate sodium caseinate micelles structure in different environments. As many natural products, Sodium Caseinate samples have large polydisperse size distribution. The experimental data was analyzed using advanced modeling approaches. The Form Factor for the Caseinate micelle subunits was described by an ellipsoidal core shell model and the structure factor was split into two contributions, one corresponding to the particle-particle interactions and another one for the long range correlation of the subunits in the supramolecular structure. For the first term the hard sphere structure factor using the Percus-Yevick approximation for closure relation was used and for the second term a fractal model was applied. Three concentrations of sodium Caseinate (2, 5 and 7.5 %wt.) were measured in pure water, sugar solutions (20 %wt.) and in three different lipid phase emulsions containing 10 %wt. sunflower seed, olive and fish oils. Data analysis provided an average casein subunit radius of 4 nm, an average distance between the subunits of around 20nm and a fractal dimension value of around 3 for all samples. As indicated by the values of the correlation lengths for the set of studied samples, the casein aggregation is strongly affected by simple sugar additions and it is enhanced by emulsion droplets hydrophobic interaction. As will be presented, these nanoscale structural results provided by scattering experiments is consistent with macroscopic results obtained from several techniques, providing a new understanding of NaCas emulsions. (author)

  4. Spectroscopic studies of interaction of Safranine T with nonionic micelles and mixed micelles.

    Chatterjee, Sujan; Bhattacharya, Subhash Chandra


    The visible spectra of Safranine T (ST) in micellar solution of Brij 58, Tween 20 and Tween 40 and mixed micellar solution of Brij 58/Tween 20 and Brij 58/Tween 40 indicate formation of 1:1 charge transfer (CT) complex between acceptor ST and donor nonionic micelles and mixed micelles. The experimental CT transition energies are well correlated (through Mulliken's equation) with the vertical ionization potential of the donors. The solvent parameters, i.e. the intramolecular charge transfer energy ET(30) have been determined from the Stokes spectral shift. Variations of ionization potential and micropolarity in the mixed micellar region have been investigated as a function of surfactant composition and the obtained results in mixed micellar medium has been compared to the normal micelles. The critical micelle concentration (CMC) values determined at various surfactant compositions are lower than the ideal values indicating a synergistic interaction. The interaction parameter (beta) and micellar stability has been calculated using regular solution theory.

  5. Molecular Exchange Dynamics in Block Copolymer Micelles

    Bates, Frank; Lu, Jie; Choi, Soohyung; Lodge, Timothy


    Poly(styrene-b-ethylene propylene) (PS-PEP) diblock copolymers were mixed with squalane (C30H62) at 1% by weight resulting in the formation of spherical micelles. The structure and dynamics of molecular exchange were characterized by synchrotron small-angle x-ray scattering (SAXS) and time resolved small-angle neutron scattering (TR-SANS), respectively, between 100 C and 160 C. TR-SANS measurements were performed with solutions initially containing deuterium labeled micelle cores and normal cores dispersed in a contrast matched squalane. Monitoring the reduction in scattering intensity as a function of time at various temperatures revealed molecular exchange dynamics highly sensitive to the core molecular weight and molecular weight distribution. Time-temperature superposition of data acquired at different temperatures produced a single master curve for all the mixtures. Experiments conducted with isotopically labeled micelle cores, each formed from two different but relatively mondisperse PS blocks, confirmed a simple dynamical model based on first order kinetics and core Rouse single chain relaxation. These findings demonstrate a dramatic transition to nonergodicity with increasing micelle core molecular weight and confirm the origins of the logarithmic exchange kinetics in such systems.




    This review presents a summary of attempts to characterize the morphology of the complexes formed between ionic and non-ionic surfactants and water-soluble polymers. It is now generally accepted that complex formation involves the binding of micelles to the macromolecule. This binding process modifi

  7. Non-diffusing radiochromic micelle gel

    Jordan, Kevin; Sekimoto, Masaya


    The addition of Laponite, a synthetic clay nanoparticle material to radiochromic leuco Malachite Green micelle hydrogel eliminates diffusion of the cationic dye by electrostatic binding. The clay nanoparticles also increased dose sensitivity ten-fold relative to the parent gel formulation. This material is a suitable 3D water equivalent dosimeter with optical CT readout.

  8. SANS analysis of aqueous ionic perfluoropolyether micelles

    Gambi, C M C; Chittofrati, A; Pieri, R; Baglioni, P; Teixeira, J


    Preliminary SANS results of ionic chlorine terminated perfluoropolyether micelles in water are given. The experimental spectra have been analyzed by a two-shell ellipsoidal model for the micellar form factor and a screened Coulombic plus hard-sphere repulsion potential for the structure factor. (orig.)

  9. Acid Hydrolysis of Bromazepam Catalyzed by Micelles, Reverse Micelles, and Microemulsions

    Ferdousi Begum


    Full Text Available Kinetics of the acid hydrolysis of bromazepam (Bz has been investigated in micelles, reverse micelles, and microemulcions of cetyltrimethylammonium bromide (CTAB by spectrophotometric method. The rate of the acid hydrolysis of Bz was found to be enhanced both below and above the critical micelle concentration (CMC of CTAB in aqueous solution. The pseudo-first-order rate constant (k′ shows an initial decrease for both low and high H+ concentrations. With further increase in [CTAB], at low [H+], the k′ attains an almost constant value, while, at high [H+], the k′ passes through a maximum and then decreases. The kinetic data for catalysis by micelles of CTAB was interpreted with the pseudophase ion exchange (PIE model. In CTAB/cyclohexane/1-butanol/water microemulsions, as the water to surfactant ratio (wo increases, the physicochemical properties and droplet sizes of microemulsions significantly change and distinct changes in reaction environment can be marked. The rate of the hydrolysis reaction exhibits excellent correlation with the physicochemical properties and droplet sizes of the microemulsions and reverse micelles of CTAB. At [H+] = 0.001 M, in reverse micelles and microemulsions of CTAB, the k′ of the acid hydrolysis of Bz decreases sharply followed by a slight increase with increasing wo.

  10. Casein micelles and their internal structure

    De Kruif, Cornelis G [ORNL; Huppertz, Thom [NIZO Food Research; Urban, Volker S [ORNL; Petukhov, Andrei V [Van ' t Hoff laboratory for Physical and Colloid Chemistry, Utrecht University, The Netherlands


    The internal structure of casein micelles was studied by calculating the small-angle neutron and X-ray scattering and static light scattering spectrum (SANS, SAXS, SLS) as a function of the scattering contrast and composition. We predicted experimental SANS, SAXS, SLS spectra self consistently using independently determined parameters for composition size, polydispersity, density and voluminosity. The internal structure of the casein micelles, i.e. how the various components are distributed within the casein micelle, was modeled according to three different models advocated in the literature; i.e. the classical sub-micelle model, the nanocluster model and the dual binding model. In this paper we present the essential features of these models and combine new and old experimental SANS, SAXS, SLS and DLS scattering data with new calculations that predict the spectra. Further evidence on micellar substructure was obtained by internally cross linking the casein micelles using transglutaminase, which led to casein nanogel particles. In contrast to native casein micelles, the nanogel particles were stable in 6 M urea and after sequestering the calcium using trisodium citrate. The changed scattering properties were again predicted self consistently. An important result is that the radius of gyration is independent of contrast, indicating that the mass distribution within a casein micelle is homogeneous. Experimental contrast is predicted quite well leading to a match point at a D{sub 2}O volume fraction of 0.41 ratio in SANS. Using SANS and SAXS model calculations it is concluded that only the nanocluster model is capable of accounting for the experimental scattering contrast variation data. All features and trends are predicted self consistently, among which the 'famous' shoulder at a wave vector value Q = 0.35 nm{sup -1}. In the nanocluster model, the casein micelle is considered as a (homogeneous) matrix of caseins in which the colloidal calcium phosphate (CCP

  11. Construction aggregates

    Nelson, T.I.; Bolen, W.P.


    Construction aggregates, primarily stone, sand and gravel, are recovered from widespread naturally occurring mineral deposits and processed for use primarily in the construction industry. They are mined, crushed, sorted by size and sold loose or combined with portland cement or asphaltic cement to make concrete products to build roads, houses, buildings, and other structures. Much smaller quantities are used in agriculture, cement manufacture, chemical and metallurgical processes, glass production and many other products.

  12. Multi-scale times and modes of fast and slow relaxation in solutions with coexisting spherical and cylindrical micelles according to the difference Becker-Döring kinetic equations

    Babintsev, Ilya A.; Adzhemyan, Loran Ts.; Shchekin, Alexander K.


    The eigenvalues and eigenvectors of the matrix of coefficients of the linearized kinetic equations applied to aggregation in surfactant solution determine the full spectrum of characteristic times and specific modes of micellar relaxation. The dependence of these relaxation times and modes on the total surfactant concentration has been analyzed for concentrations in the vicinity and well above the second critical micelle concentration (cmc2) for systems with coexisting spherical and cylindrical micelles. The analysis has been done on the basis of a discrete form of the Becker-Döring kinetic equations employing the Smoluchowsky diffusion model for the attachment rates of surfactant monomers to surfactant aggregates with matching the rates for spherical aggregates and the rates for large cylindrical micelles. The equilibrium distribution of surfactant aggregates in solution has been modeled as having one maximum for monomers, another maximum for spherical micelles and wide slowly descending branch for cylindrical micelles. The results of computations have been compared with the analytical ones known in the limiting cases from solutions of the continuous Becker-Döring kinetic equation. They demonstrated a fair agreement even in the vicinity of the cmc2 where the analytical theory looses formally its applicability.

  13. SAAS-CNV: A Joint Segmentation Approach on Aggregated and Allele Specific Signals for the Identification of Somatic Copy Number Alterations with Next-Generation Sequencing Data.

    Zhongyang Zhang


    Full Text Available Cancer genomes exhibit profound somatic copy number alterations (SCNAs. Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1 extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2 performing joint segmentation on the two signal dimensions; 3 correcting the copy number baseline from which the SCNA state is determined; 4 calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity.

  14. SAAS-CNV: A Joint Segmentation Approach on Aggregated and Allele Specific Signals for the Identification of Somatic Copy Number Alterations with Next-Generation Sequencing Data.

    Zhang, Zhongyang; Hao, Ke


    Cancer genomes exhibit profound somatic copy number alterations (SCNAs). Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1) extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2) performing joint segmentation on the two signal dimensions; 3) correcting the copy number baseline from which the SCNA state is determined; 4) calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS) as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity.

  15. Spectroscopic Characterization of Intermolecular Interaction of Amyloid β Promoted on GM1 Micelles

    Maho Yagi-Utsumi


    Full Text Available Clusters of GM1 gangliosides act as platforms for conformational transition of monomeric, unstructured amyloid β (Aβ to its toxic β-structured aggregates. We have previously shown that Aβ(1–40 accommodated on the hydrophobic/hydrophilic interface of lyso-GM1 or GM1 micelles assumes α-helical structures under ganglioside-excess conditions. For better understanding of the mechanisms underlying the α-to-β conformational transition of Aβ on GM1 clusters, we performed spectroscopic characterization of Aβ(1–40 titrated with GM1. It was revealed that the thioflavin T- (ThT- reactive β-structure is more populated in Aβ(1–40 under conditions where the Aβ(1–40 density on GM1 micelles is high. Under this circumstance, the C-terminal hydrophobic anchor Val39-Val40 shows two distinct conformational states that are reactive with ThT, while such Aβ species were not generated by smaller lyso-GM1 micelles. These findings suggest that GM1 clusters promote specific Aβ-Aβ interactions through their C-termini coupled with formation of the ThT-reactive β-structure depending on sizes and curvatures of the clusters.

  16. Preparation and Evaluation of Inhalable Itraconazole Chitosan Based Polymeric Micelles

    Esmaeil Moazeni


    Full Text Available Background: This study evaluated the potential of chitosan based polymeric micelles as a nanocarrier system for pulmonary delivery of itraconazole (ITRA.Methods: Hydrophobically modified chitosan were synthesized by conjugation of stearic acid to the hydrophilic depolymerized chitosan. FTIR and 1HNMR were used to prove the chemical structure and physical properties of the depolymerized and the stearic acid grafted chitosan. ITRA was entrapped into the micelles and physicochemical properties of the micelles were investigated. Fluorescence spectroscopy, dynamic laser light scattering andtransmission electron microscopy were used to characterize the physicochemical properties of the prepared micelles. The in vitro pulmonary profile of polymeric micelles was studied by an air-jet nebulizer connected to a twin stage impinger.Results: The polymeric micelles prepared in this study could entrap up to 43.2±2.27 μg of ITRA per milliliter. All micelles showed mean diameter between 120–200 nm. The critical micelle concentration of the stearic acid grafted chitosan was found to be 1.58×10-2 mg/ml. The nebulization efficiency was up to 89% and the fine particle fraction (FPF varied from 38% to 47%. The micelles had enough stability to remain encapsulation of the drug during nebulization process.Conclusions: In vitro data showed that stearic acid grafted chitosan based polymeric micelles has a potential to be used as nanocarriers for delivery of itraconazole through inhalation.

  17. Cooperative catalysis with block copolymer micelles: a combinatorial approach.

    Bukhryakov, Konstantin V; Desyatkin, Victor G; O'Shea, John-Paul; Almahdali, Sarah R; Solovyeva, Vera; Rodionov, Valentin O


    A rapid approach to identifying complementary catalytic groups using combinations of functional polymers is presented. Amphiphilic polymers with "clickable" hydrophobic blocks were used to create a library of functional polymers, each bearing a single functionality. The polymers were combined in water, yielding mixed micelles. As the functional groups were colocalized in the hydrophobic microphase, they could act cooperatively, giving rise to new modes of catalysis. The multipolymer "clumps" were screened for catalytic activity, both in the presence and absence of metal ions. A number of catalyst candidates were identified across a wide range of model reaction types. One of the catalytic systems discovered was used to perform a number of preparative-scale syntheses. Our approach provides easy access to a range of enzyme-inspired cooperative catalysts.

  18. Cooperative catalysis with block copolymer micelles: A combinatorial approach

    Bukhryakov, Konstantin V.


    A rapid approach to identifying complementary catalytic groups using combinations of functional polymers is presented. Amphiphilic polymers with "clickable" hydrophobic blocks were used to create a library of functional polymers, each bearing a single functionality. The polymers were combined in water, yielding mixed micelles. As the functional groups were colocalized in the hydrophobic microphase, they could act cooperatively, giving rise to new modes of catalysis. The multipolymer "clumps" were screened for catalytic activity, both in the presence and absence of metal ions. A number of catalyst candidates were identified across a wide range of model reaction types. One of the catalytic systems discovered was used to perform a number of preparative-scale syntheses. Our approach provides easy access to a range of enzyme-inspired cooperative catalysts.

  19. Biodegradable polyurethane micelles with pH and reduction responsive properties for intracellular drug delivery.

    Guan, Yayuan; Su, Yuling; Zhao, Lili; Meng, Fancui; Wang, Quanxin; Yao, Yongchao; Luo, Jianbin


    Polyurethane micelles with disulfide linkage located at the interface of hydrophilic shell and hydrophobic core (PU-SS-I) have been shown enhanced drug release profiles. However, the payloads could not be released completely. The occurrence of aggregation of hydrophobic cores upon shedding hydrophilic PEG coronas was considered as the reason for the incomplete release. To verify the above hypothesis and to develop a new polyurethane based micelles with dual stimuli respond properties and controllable location of pH and reduction responsive groups in the PU main chains, a tertiary amine was incorporated into the hydrophobic core PU-SS-I, which resulted polyurethane with both reduction and pH sensitive properties (PU-SS-N). Biodegradable polyurethane with only disulfide linkages located between the hydrophilic PEG segment and the hydrophobic PCL segments (PU-SS-I) and polyurethane with only pH sensitive tertiary amine at the hydrophobic core (PU-N-C) were used as comparisons. Paclitaxel (PTX) was chosen as mode hydrophobic drug to evaluate the loading and redox triggered release profiles of the PU micelles. It was demonstrated that PU-SS-N micelles disassembled instantly at the presence of 10mM GSH and at an acidic environment (pH=5.5), which resulted the nearly complete release (~90%) of the payloads within 48h, while about ~70% PTX was released from PU-SS-I and PU-SS-N micelles at neutral environment (pH=7.4) with the presence of 10mM GSH. The rapid and complete redox and pH stimuli release properties of the PU-SS-N nanocarrier will be a promising anticancer drug delivery system to ensure sufficient drug concentration to kill the cancer cells and to prevent the emergency of MDR. The in vitro cytotoxicity and cell uptake of the PTX-loaded micelles was also assessed in H460 and HepG2 cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Effect of 1-Butyl-3-methylimidazolium Halide on the Relative Stability between Sodium Dodecyl Sulfate Micelles and Sodium Dodecyl Sulfate-Poly(ethylene oxide) Nanoaggregates.

    Ferreira, Gabriel M Dias; Ferreira, Guilherme M Dias; Agudelo, Álvaro J Patiño; Hespanhol da Silva, Maria C; Rezende, Jaqueline de Paula; Pires, Ana Clarissa Dos Santos; da Silva, Luis Henrique Mendes


    It is well-known that ionic liquids (ILs) alter the properties of aqueous systems containing only surfactants. However, the effect of ILs on polymer-surfactant systems is still unknown. Here, the effect of 1-butyl-3-methylimidazolium bromide (bmimBr) and chloride (bmimCl) on the micellization of sodium dodecyl sulfate (SDS) and its interaction with poly(ethylene oxide) (PEO) was evaluated using conductimetry, fluorimetry, and isothermal titration calorimetry. The ILs decreased the critical micellar concentration (cmc) of the surfactant, stabilizing the SDS micelles. A second critical concentration (c2thc) was verified at high SDS concentrations, due to the micelle size decrease. The stability of PEO/SDS aggregates was also affected by ILs, and the critical aggregation concentration (cac) of SDS increased. Integral aggregation enthalpy changed from -0.72 in water to 2.16 kJ mol(-1) in 4.00 mM bmimBr. IL anions did not affect the SDS micellization or the beginning of PEO/SDS aggregation. Nevertheless, when chloride was replaced with bromide, the amount of SDS bound to the polymer increased. At 100.0 mM IL, the PEO-SDS interaction vanished. We suggest that the effect of ILs comes from participating in the structure of the formed aggregates, interacting with the SDS monomers at the core/interface of the micelles, and promoting preferential solvation of the polymer.

  1. On the stability and morphology of complex coacervate core micelles: from spherical to wormlike micelles.

    van der Kooij, Hanne M; Spruijt, Evan; Voets, Ilja K; Fokkink, Remco; Cohen Stuart, Martien A; van der Gucht, Jasper


    We present a systematic study of the stability and morphology of complex coacervate core micelles (C3Ms) formed from poly(acrylic acid) (PAA) and poly(N-methyl-2-vinylpyridinium)-b-poly(ethylene oxide) (PM2VP-b-PEO). We use polarized and depolarized dynamic and static light scattering, combined with small-angle X-ray scattering, to investigate how the polymer chain length and salt concentration affect the stability, size, and shape of these micelles. We show that C3Ms are formed in aqueous solution below a critical salt concentration, which increases considerably with increasing PAA and PM2VP length and levels off for long chains. This trend is in good agreement with a mean-field model of polyelectrolyte complexation based on the Voorn-Overbeek theory. In addition, we find that salt induces morphological changes in C3Ms when the PAA homopolymer is sufficiently short: from spherical micelles with a diameter of several tens of nanometers at low salt concentration to wormlike micelles with a contour length of several hundreds of nanometers just before the critical salt concentration. By contrast, C3Ms of long PAA homopolymers remain spherical upon addition of salt and shrink slightly. A critical review of existing literature on other C3Ms reveals that the transition from spherical to wormlike micelles is probably a general phenomenon, which can be rationalized in terms of a classical packing parameter for amphiphiles.

  2. 葡萄糖对脱脂乳酪蛋白胶束稳定性的影响研究%Study on the influence of glucose on the stability of casein micelles in skim milk

    杨敏; 梁琪; 乔海军; 张卫兵; 孙雪燕; 甘伯中


    摘要:研究了葡萄糖添加量、体系pH、热处理温度、热处理时间对脱脂牛乳酪蛋白胶束稳定性的影响。研究表明,在接近中性pH条件下,少量葡萄糖分子可降低脱脂乳酪蛋白胶束的稳定性,大量葡萄糖分子可增强其稳定性。添加葡萄糖后,在高温热处理的诱导下,酪蛋白沉淀的pH升高。随着热处理时间的延长,脱脂乳中酪蛋白胶束表现出聚集行为.致使粒径增大.浊度和沉淀率总体呈现上升趋势。该研究结论可为乳品加工提供参考依据。%The influence of the glucose amount,the system pH,the heat treatment temperature,the heat treatment time on the stability of casein micelles of skim milk were studied. The result showed that,nearly neutral pH,the stability of skim milk casein micelles was reduced with a small amount of glucose,which was increased with a large number of glucose. The pH of the casein precipitation was increased by adding glucose on the high temperature heat treatment. With the extension of the heat treatment time,casein micelles showed aggregation behavior,the particle size was increased,which induced the turbidity and sedimentation amount upward. The conclusion would provide a reference for the dairy processing.

  3. Determination of aggregation thresholds of UV absorbing anionic surfactants by frontal analysis continuous capillary electrophoresis.

    Le Saux, Thomas; Varenne, Anne; Gareil, Pierre


    Aggregation of anionic surfactants was investigated by frontal analysis continuous capillary electrophoresis (FACCE), a method involving the continuous electrokinetic introduction of the surfactant sample into the separation capillary. This process results in a partial separation of the monomeric and aggregated forms without perturbing the monomer-aggregate equilibrium. The critical micelle concentration (CMC) can then be easily derived from the height of the firstly detected migration front, corresponding to the monomeric form. This approach is exemplified with octyl and dodecylbenzenesulfonates and compared with conductimetry and surface tension measurements. FACCE turns out to be an effective method for the determination of CMC and intermediate aggregation phenomena with very small sample and short time requirements.

  4. Review on aggregation of acid extractants in solvent extraction of metal ions: remark on the general model


    The aggregation behavior of various acid extractants in the solvent extraction systems of metal ions is re-examined and explained according to knowledge obtained in recent work. The conclusions are as follows. (1) Complexes formed by the extractants and metal ions can form reversed micelles in organic diluents, depending on the microstructures of the complexes. The dimers of the acid extractant cannot percolate to the metal-extractant aggregates, and the acid-salt complexes are always formed in the aggregates. The reversed micelles or the W/O microemulsions formed by different species cannot be associated with each other to form a unified aggregate. (2) In solvent extraction systems, hydration of the extractants and metal ions can be considered as the driving force of forming reversed micelles. (3) Information of the first approach to the insight of the bicontinuous microemulsion of NaDEHP shows that various components in the aqueous phase behave confined and very similar to the typical AOT/n-heptane W/O microemulsions. (4) In the extraction of lanthanide ions by the W/O microemulsion of sodium naphthenate, the saponification is a process of forming reversed micelle or W/O microemulsion, while the extraction step is a process of destroying reversed micelles or W/O microemulsion droplets.

  5. The renneting of milk : a kinetic study of the enzymic and aggregation reactions

    Hooydonk, van A.C.M.


    The rennet-induced clotting of milk was studied under various conditions. The kinetics of the enzymic and aggregation reactions was analysed separately and, where possible, related to the physico-chemical properties of the casein micelle and its environment.

    The effects of important

  6. Competitive solubilization of phenol by cationic surfactant micelles in the range of low additive and surfactant concentrations.

    Chaghi, Radhouane; de Ménorval, Louis-Charles; Charnay, Clarence; Derrien, Gaëlle; Zajac, Jerzy


    Competitive interactions of phenol (PhOH) with micellar aggregates of hexadecyltrimethylammonium bromide (HTAB) against 1-butanol (BuOH) in aqueous solutions at surfactant concentrations close to the critical micelle concentration (CMC), BuOH concentration of 0.5 mmol kg(-1), and phenol contents of 1, 5, or 10 mmol kg(-1) have been investigated at 303 K by means of (1)H NMR spectroscopy, titration calorimetry, and solution conductimetry. The solubilization loci for phenol were deduced from the composition-dependence of the (1)H chemical shifts assigned to various protons in the surfactant and additive units. Since in pure HTAB solutions phenol is already in competition with Br(-), addition of 1 mmol kg(-1) NaBr to the system weakens the phenol competitiveness. The presence of butanol in the HTAB micelles causes phenol to penetrate deeper toward the hydrophobic micelle core. For higher phenol contents, the butanol molecules are constrained to remain in the bulk solution and are progressively replaced within the HTAB micelles by the aromatic units. The competitive character of phenol solubilization against butanol is well supported by changes in the thermodynamic parameters of HTAB micellization in the presence of both of the additives.

  7. Chain exchange in triblock copolymer micelles

    Lu, Jie; Lodge, Timothy; Bates, Frank


    Block polymer micelles offer a host of technological applications including drug delivery, viscosity modification, toughening of plastics, and colloidal stabilization. Molecular exchange between micelles directly influences the stability, structure and access to an equilibrium state in such systems and this property recently has been shown to be extraordinarily sensitive to the core block molecular weight in diblock copolymers. The dependence of micelle chain exchange dynamics on molecular architecture has not been reported. The present work conclusively addresses this issue using time-resolved small-angle neutron scattering (TR-SANS) applied to complimentary S-EP-S and EP-S-EP triblock copolymers dissolved in squalane, a selective solvent for the EP blocks, where S and EP refer to poly(styrene) and poly(ethylenepropylene), respectively. Following the overall SANS intensity as a function of time from judiciously deuterium labelled polymer and solvent mixtures directly probes the rate of molecular exchange. Remarkably, the two triblocks display exchange rates that differ by approximately ten orders of magnitude, even though the solvophobic S blocks are of comparable size. This discovery is considered in the context of a model that successfully explains S-EP diblock exchange dynamics.

  8. Headgroup effects on the Krafft temperatures and self-assembly of ω-hydroxy and ω-carboxy hexadecyl quaternary ammonium bromide bolaform amphiphiles: micelles versus molecular clusters?

    Holder, Simon J; Sriskantha, Bruntha C; Bagshaw, Stephen A; Bruce, Ian J


    Eight bolaform amphiphiles were synthesised and characterised; 4 α,ω-hydroxy-alkane trialkyl (and pyridyl) ammonium bromides and 4 α,ω-carboxy-alkane trialkyl (and pyridyl) ammonium bromides where the alkyl groups were methyl, ethyl and propyl. Four of these represented new compounds. Overall the Krafft temperatures (T(K)) of the eight amphiphiles were high, with 6 of the eight possessing T(K)s greater than 45 °C. Thus most of the amphiphiles could only expect to find applications at raised temperatures limiting their potential utility. However in addition to the previously reported α,ω-hydroxy-hexadecyl triethylammonium bromide (2b) with a T(K) of 19.1 °C, another amphiphile, α,ω-carboxy-hexadecyl tripropylammonium bromide (2c) has been identified with a T(K) near ambient temperatures (T(K) of 22.1 °C). This provides an acid functional ammonium bolaform amphiphile that micellises at ambient temperatures to complement the hydroxyl derivative. A correlation between T(K) and the product of the enthalpies and T(m)s of the compounds was observed for 7 of the eight compounds. No correlation between the amphiphile critical micelle concentrations (cmc) and T(K)s was observed confirming previous reports that T(K) values are predominantly determined by crystalline stability rather than solubility. Considerable differences were observed between the various amphiphile T(K)s at different pHs but no clear trend was apparent for the various compounds (despite the degree to which the compounds' carboxylic acid and hydroxyl functionalities were likely to be ionised). The cmcs for the amphiphiles were an order of magnitude larger than those for analogous mono-ammonium amphiphiles with little difference in between the hydroxyl- and carboxy-functionalised compounds. The aggregation numbers (N(agg)) obtained for all compounds were very low (N(agg)bolaforms were in the range 1.0-1.4 nm whereas those for the carboxy-compounds were in the range 2.1-2.4 nm. These results

  9. Self-assembled or mixed peptide amphiphile micelles from Herpes simplex virus glycoproteins as potential immunomodulatory treatment

    Accardo A


    Full Text Available Antonella Accardo,1 Mariateresa Vitiello,2,3 Diego Tesauro,1 Marilena Galdiero,2 Emiliana Finamore,2 Francesca Martora,2 Rosalba Mansi,1 Paola Ringhieri,1 Giancarlo Morelli11Department of Pharmacy, Interuniversitary Centre for Research on Bioactive peptides, CIRPeB, University of Naples "Federico II", Institute of Biostructures and Bioimaging IBB-CNR, Naples, Italy; 2Department of Experimental Medicine, Section of Microbiology and Clinical Microbiology, Second University of Naples, Naples, Italy; 3Department of Clinical Pathology and Transfusion Medicine, University Hospital “Ruggi d'Aragona”, Salerno, ItalyAbstract: The use of micelle aggregates formed from peptide amphiphiles (PAs as potential synthetic self-adjuvant vaccines to treat Herpes simplex virus (HSV infection are reported here. The PAs were based on epitopes gB409-505 and gD301-309, selected from HSV envelope glycoprotein B (gB and glycoprotein D (gD, that had their N-terminus modified with hydrophobic moieties containing two C18 hydrocarbon chains. Pure and mixed micelles of gB and/or gD peptide epitopes were easily prepared after starting with the synthesis of corresponding PAs by solid phase methods. Structural characterization of the aggregates confirmed that they were sufficiently stable and compatible with in vivo use: critical micelle concentration values around 4.0 · 10-7 mol · Kg-1; hydrodynamic radii (RH between 50–80 nm, and a zeta potential (ζ around – 40 mV were found for all aggregates. The in vitro results indicate that both peptide epitopes and micelles, at 10 µM, triggered U937 and RAW 264.7 cells to release appreciable levels of cytokines. In particular, interleukin (IL-23-, IL-6-, IL-8- or macrophage inflammatory protein (MIP-2-, and tumor necrosis factor (TNF-α-release increased considerably when cells were treated with the gB-micelles or gD-micelles compared with the production of the same cytokines when the stimulus was the single gB or gD peptide

  10. Sequence-dependent internalization of aggregating peptides.

    Couceiro, José R; Gallardo, Rodrigo; De Smet, Frederik; De Baets, Greet; Baatsen, Pieter; Annaert, Wim; Roose, Kenny; Saelens, Xavier; Schymkowitz, Joost; Rousseau, Frederic


    Recently, a number of aggregation disease polypeptides have been shown to spread from cell to cell, thereby displaying prionoid behavior. Studying aggregate internalization, however, is often hampered by the complex kinetics of the aggregation process, resulting in the concomitant uptake of aggregates of different sizes by competing mechanisms, which makes it difficult to isolate pathway-specific responses to aggregates. We designed synthetic aggregating peptides bearing different aggregation propensities with the aim of producing modes of uptake that are sufficiently distinct to differentially analyze the cellular response to internalization. We found that small acidic aggregates (≤500 nm in diameter) were taken up by nonspecific endocytosis as part of the fluid phase and traveled through the endosomal compartment to lysosomes. By contrast, bigger basic aggregates (>1 μm) were taken up through a mechanism dependent on cytoskeletal reorganization and membrane remodeling with the morphological hallmarks of phagocytosis. Importantly, the properties of these aggregates determined not only the mechanism of internalization but also the involvement of the proteostatic machinery (the assembly of interconnected networks that control the biogenesis, folding, trafficking, and degradation of proteins) in the process; whereas the internalization of small acidic aggregates is HSF1-independent, the uptake of larger basic aggregates was HSF1-dependent, requiring Hsp70. Our results show that the biophysical properties of aggregates determine both their mechanism of internalization and proteostatic response. It remains to be seen whether these differences in cellular response contribute to the particular role of specific aggregated proteins in disease.

  11. Neutron scattering characterization of homopolymers and graft-copolymer micelles in supercritical carbon dioxide

    Chillura-Martino, D; Triolo, R. [Palermo Univ. (Italy). Ist. di Chimica Fisica; McClain, J.B. [North Carolina Univ., Chapel Hill, NC (United States)] [and others


    Supercritical fluids are becoming an attractive alternative to the liquid solvents traditionally used as polymerization media. As the synthesis proceeds, a wide range of colloidal aggregates form, but there has hitherto been no way to measure such structures directly. We have applied small-angle neutron scattering (SANS) to characterize such systems, and although SCF polymerizations are carried out at high pressures, the penetrating power of the neutron beam means that typical cell windows are virtually transparent. Systems studied include molecules soluble in CO{sub 2} (e.g. polyfluoro-octyl acrylate or PFOA) and this polymer has previously been shown to exhibit a positive second virial coefficient (A{sub 2}). Other CO{sub 2}-soluble polymers include hexafluoro-polypropylene oxide (HFPPO), which appears to have a second virial coefficient which is close to zero (10{sup 4}A{sub 2} {approx_equal} 0 +{+-} 0.2 cm{sup 3} g{sup -2} mol). Polydimethylsiloxane (PDMS), is soluble on the molecular level only in the limit of dilute solution and seems to form aggregates as the concentration increases (c > 0.01 g cm{sup -3}). Other polymers (e.g. polystyrene) are insoluble in CO{sub 2}, though polymerizations may be accomplished via the use of PS-PFOA blockcopolymer stabilizers, which are also amenable to SANS characterization, and have been shown to form micelles in CO{sub 2}. Other amphiphilic surfactant molecules that form micelles include PFOA-polyethylene oxide (PFOA-PEO) graft copolymers, which swell as the CO{sub 2} medium is saturated with water. These systems have been characterized by SANS, by taking advantage of the different contrast options afforded by substituting D{sub 2}O for H{sub 2}O. This paper illustrates the utility of SANS to measure molecular dimensions, thermodynamic variables, molecular weights, micelle structures etc. in supercritical CO{sub 2}.

  12. Micelles and gels of oxyethylene-oxybutylene diblock copolymers in aqueous solution: The effect of oxyethylene-block length

    Derici, L.; Ledger, S.; Mai, S.M.


    Block copolymer E(90)B(10) (E = oxyethylene, B = oxybutylene) was synthesised and characterised by gel permeation chromatography and (13)C NMR spectroscopy. Dynamic light scattering (DLS) and static light scattering (SLS) were used to characterise the micelles in solution (both in water and in aq......Block copolymer E(90)B(10) (E = oxyethylene, B = oxybutylene) was synthesised and characterised by gel permeation chromatography and (13)C NMR spectroscopy. Dynamic light scattering (DLS) and static light scattering (SLS) were used to characterise the micelles in solution (both in water.......e., the association number, the hard-sphere radius, the micelle volume fraction and the corresponding expansion factors. A comparison of the appropriate quantities showed good agreement between the two techniques. SANS gave additional information e.g., volume fraction profiles for the micelles and volume fraction...... of water in the micelle core. Moderately concentrated solutions of copolymer E(90)B(10) were studied in the gel state by small-angle X-ray scattering (SAXS) in tandem with rheology (oscillatory shear). Values for the dynamic elastic modulus (G') of the gels significantly exceeded 10(4) Pa across the range...

  13. In vitro evaluation of pH-sensitive cholesterol-containing stable polymeric micelles for delivery of camptothecin.

    Laskar, Partha; Samanta, Sintu; Ghosh, Sudip Kumar; Dey, Joykrishna


    Two novel amphiphilic statistical copolymers poly(cholesteryl acrylate-co-methoxypoly(ethylene glycol) methacrylate), poly[CHOL(y)-co-mPEG(n,x)] (for n=5, x=110 and y=15, and for n=23, x=22 and y=3) with copolymer composition (x:y) of 7:1 were designed and synthesized as a delivery system for water-insoluble anticancer agent, S-(+)-camptothecin (CPT). The polymers were synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization technique and they were found to form stable polymeric micelles in water above a relatively low critical concentration. The polymeric micelles (PMs) were characterized by a number of techniques including surface tension, fluorescence, dynamic light scattering, and electron microscopy. Incorporation of CPT into the micelles and the stability of CPT-loaded micelles were studied by spectrophotometric method. Sustained release of an encapsulated fluorescent guest triggered by hydrolysis of the ester linkages in acidic pH is demonstrated. The polymers are not only hemocompatible and nontoxic in the allowed concentration range, but also they can easily permeate into the cancer cells (MCF7 and HeLa). The in vitro drug delivery assay of CPT-loaded polymeric micelles on cancer cells (HeLa) showed very good chemotherapeutic activity in the biocompatible concentration range of the copolymers. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Stimuli-responsive biodegradable polymeric micelles for targeted cancer therapy

    Talelli, M.A.


    Thermosensitive and biodegradable polymeric micelles based on mPEG-b-pHPMAmLacn have shown very promising results during the past years. The results presented in this thesis illustrate the high potential of these micelles for anticancer therapy and imaging and fully justify further pharmaceutical


    Xiao-chun Qin; Chun-lai Ren


    Combining self-consistent-field theory and density-functional theory,we systematically study the deformation of copolymer micelles induced by the presence of amphiphilic dimer particles.Due to the amphiphilic nature,dimer particles tend to accumulate onto the interface of the copolymer micelle.With increasing concentration of the symmetric dimer particles,which are made of two identical spherical particles,the micelle deforms from the initial sphere to ellipse,dumbbell,and finally separates into two micelles.Furthermore,asymmetric dimer particles,composed by two particles with different sizes,are considered to investigate the influence of geometry of dimer particles on the deformation of the micelle.It is found that the micelle inclines to deform into dumbbell due to the additional curvature originating in the gathering of asymmetric dimer particles onto the interface of the micelle.The present study on the deformation of micelles is useful to understand the possible shape variation in the course of cell division/fusion.

  16. Absorption Complex between Porphyrin and Phenothiazine in Reverse Micelles


    The interaction between amphiphilic porphyrin and phenothiazine in AOT/isooctane/ water reverse micelle was investigated by UV-Vis spectra. A new absorption complex between the two species is formed in such circumstances, which is ascribed to the enrichment of the components by the reverse micelle. The fluorescence quenching of CHTTP by PTH becomes more efficient after the formation of the absorption complex.

  17. Anthracene functionalized thermosensitive and UV-crosslinkable polymeric micelles

    Shi, Yang; Cardoso, Renata M.; Van Nostrum, Cornelus F.; Hennink, Wim E.


    An anthracene-functionalized thermosensitive block copolymer was synthesized, which formed micelles by heating its aqueous solution above the lower critical solution temperature (LCST). The micelles were subsequently crosslinked by UV illumination at 365 nm with a normal handheld UV lamp. The micell

  18. Structure and stability of complex coacervate core micelles with lysozyme

    Lindhoud, Saskia; de Vries, Renko; Norde, Willem; Cohen Stuart, Martien A.

    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA(42)PAAm(417)

  19. Structure and Stability of Complex Coacervate Core Micelles with Lysozyme

    Lindhoud, Saskia; de Vries, Renko; Norde, Willem; Cohen Stuart, Martinus Abraham


    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and

  20. Structure and stability of complex coacervate core micelles with lysozyme

    Lindhoud, S.; Vries, de R.J.; Norde, W.; Cohen Stuart, M.A.


    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and th

  1. Designing Dendrimers to Offer Micelle-Type Nanocontainers

    King, Angela G.


    The properties of a dendrimer with hydrophobic and hydrophilic substituents on an orthogonal plane is synthesized and studied. The resulting polymer contains one of the substituents in its concave interior and the other at the convex surface and the design promotes micelle-like behavior in polar solvent and inverted micelle arrangement in…

  2. Lactoferrin binding to transglutaminase cross-linked casein micelles

    Anema, S.G.; de Kruif, C.G.


    Casein micelles in skim milk were either untreated (untreated milk) or were cross-linked using transglutaminase (TGA-milk). Added lactoferrin (LF) bound to the casein micelles and followed Langmuir adsorption isotherms. The adsorption level was the same in both milks and decreased the micellar zeta

  3. Structure and Stability of Complex Coacervate Core Micelles with Lysozyme

    Lindhoud, Saskia; Vries, de Renko; Norde, Willem; Cohen Stuart, Martien A.


    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and th

  4. Structure and stability of complex coacervate core micelles with lysozyme

    Lindhoud, Saskia; de Vries, Renko; Norde, Willem; Cohen Stuart, Martien A.


    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA(42)PAAm(417) an

  5. Photoinduced charge separation and enzyme reactions in reversed micelles.

    Verhaert, R.M.D.


    In this thesis the performance and coupling of two types of reaction, photoinduced charge separation and enzymatic conversion were studied in reversed micelles. Reversed micelles are 1 to 10 nm sized water droplets dispersed in an organic solution. The dispersant is a detergent (cationogenic, nonion

  6. Magainin II modified polydiacetylene micelles for cancer therapy

    Yang, Danling; Zou, Rongfeng; Zhu, Yu; Liu, Ben; Yao, Defan; Jiang, Juanjuan; Wu, Junchen; Tian, He


    Polydiacetylene (PDA) micelles have been widely used to deliver anticancer drugs in the treatment of a variety of tumours and for imaging living cells. In this study, we developed an effective strategy to directly conjugate magainin II (MGN-II) to the surface of PDA micelles using a fluorescent dye. These stable and well-defined PDA micelles had high cytotoxicity in cancer cell lines, and were able to reduce the tumour size in mice. The modified PDA micelles improved the anticancer effects of MGN-II in the A549 cell line only at a concentration of 16.0 μg mL-1 (IC50). In addition, following irradiation with UV light at 254 nm, the PDA micelles gave rise to an energy transfer from the fluorescent dye to the backbone of PDA micelles to enhance the imaging of living cells. Our results demonstrate that modified PDA micelles can not only be used in the treatment of tumors in vitro and in vivo in a simple and directed way, but also offer a new platform for designing functional liposomes to act as anticancer agents.Polydiacetylene (PDA) micelles have been widely used to deliver anticancer drugs in the treatment of a variety of tumours and for imaging living cells. In this study, we developed an effective strategy to directly conjugate magainin II (MGN-II) to the surface of PDA micelles using a fluorescent dye. These stable and well-defined PDA micelles had high cytotoxicity in cancer cell lines, and were able to reduce the tumour size in mice. The modified PDA micelles improved the anticancer effects of MGN-II in the A549 cell line only at a concentration of 16.0 μg mL-1 (IC50). In addition, following irradiation with UV light at 254 nm, the PDA micelles gave rise to an energy transfer from the fluorescent dye to the backbone of PDA micelles to enhance the imaging of living cells. Our results demonstrate that modified PDA micelles can not only be used in the treatment of tumors in vitro and in vivo in a simple and directed way, but also offer a new platform for

  7. Effect of temperature, water content and free fatty acid on reverse micelle formation of phospholipids in vegetable oil.

    Lehtinen, Olli-Pekka; Nugroho, Robertus Wahyu N; Lehtimaa, Tuula; Vierros, Sampsa; Hiekkataipale, Panu; Ruokolainen, Janne; Sammalkorpi, Maria; Österberg, Monika


    The self-assembly of phospholipids in oil, specifically lecithin in rapeseed oil, was investigated by combining experimental and computational methods The influence of temperature, water, and free fatty acids on the onset of lecithin aggregation in the rapeseed oil was determined using the 7,7,8,8 -tetracyanoquinodimethane dye (TCNQ) solubilization method and the size and shape of the self-assembled lecithin structures were investigated by small-angle X-ray scattering and cryogenic transmission electron microscopy. In the absence of excess water in the system (0.03wt-% water in oil), stable cylindrical lecithin reverse micelles were observed above the critical micelle concentration (CMC). Comparing the aggregation response in room temperature and at 70°C revealed that CMC decreased with increasing temperature. Furthermore, already a modest amount of added water (0.3wt-% water in oil) was sufficient to induce the formation of lamellar lecithin structures, that phase separated from the oil. In low water content, oleic acid suppressed the formation of lecithin reverse micelles whereas in the presence of more water, the oleic acid stabilized the reverse micelles. Consequently, more water was needed to induce phase separation in the presence of oleic acid. Molecular dynamics simulations indicated that the stabilizing effect of oleic acid resulted from oleic acid enhancing phospholipid solubilization in the oil by forming a solvating shell around the phosphate head group. The findings showed that the response of the mixed surfactant system is a delicate interplay of the different components and variables. The significance of the observations is that multiple parameters need to be controlled for desired system response, for example towards vegetable oil purification or phospholipid based microemulsions. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Studies on properties of different reverse micelles%不同反胶束体系特性研究

    杨颖莹; 布冠好; 陈复生; 廖志雄


      该实验旨在研究不同反胶束体系性质,测定丁二酸二异辛酯磺酸钠(AOT)/异辛烷单一反胶束溶液及丁二酸二异辛酯磺酸钠(AOT)―吐温85(Tween 85)/异辛烷―正辛醇混合反胶束溶液的含水量(Wo)、粘度及电导率。结果显示,在相同含水量(Wo)条件下,AOT–Tween 85混合反胶束粘度及电导率均大于AOT单一反胶束溶液;AOT反胶束溶液粘度随含水量增加呈先增加后降低,而AOT–Tween 85反胶束溶液粘度随含水量增加而增大;两种不同反胶束体系电导率均随含水量增加而先增加后降低,混合反胶束体系随AOT比例增大,电导率最大时含水量(Wo,max)向Wo值更大方向移动。通过实验结果表明,由于Wo增大,反胶束之间分子间作用力增强,从而增加反胶束聚集数,粘度随之增加;但两种反胶束体系区别主要是由于增溶水能力不同;电导率也可反映胶束化行为;在相同条件下,AOT–Tween 85反胶束“水池”直径大于AOT反胶束“水池”直径。%  This experiment is designed to study the properties of different reverse micelle ,and determine Wo,viscosity and conductivity value of AOT/isooctane single reverse micelle system and AOT–Tween 85/isooctane–n–octyl alcohol mixed reverse micelle system. Results show that,on the same Wo conditions,the viscosity of AOT–Tween 85 mixed reverse micelle is greater than AOT single reverse micelle. The viscosity of AOT reverse micelle increased and then reduced with the increase of Wo,but AOT–Tween 85 reverse micelle increased. The conductivity value of two different reverse micelle system are increased and then decreased with the increase of Wo,and the Wo,max of AOT–Tween 85 conductivity value moved to a bigger Wo value as the mass ratio of the AOT increased. The experimental results show that,due to the increase of Wo,reverse micelle inter–atomic forces increase between molecules,thus the number of gathered reverse

  9. Polymer Micelles Laden Hydrogel Contact Lenses for Ophthalmic Drug Delivery.

    Hu, Xiaohong; Tan, Huaping; Chen, Pin; Wang, Xin; Pang, Juan


    Hydrogel contact lens is an attractive drug carrier for the delivery of ophthalmic drugs. But limited drug loading capacity and burst release restricted its application in this field. Polymer micelle laden hydrogel contact lenses were designed for ophthalmic drug delivery in the work. β-CD/PAA/PEG ternary system was chosen to form polymer micelle. The micelle size could be adjusted by β-CD content and PAA/PEG concentration. The zeta potential of micelle was irrelevant to β-CD content, but influenced by PAA/PEG concentration. The absorbed drug concentration in micelle solution depended on both β-CD content and PAA/PEG concentration. Polymer micelle laden hydrogels were obtained by radical polymerization in situ. The transparency of polymer micelle laden hydrogel declined with PAA/PEG concentration increasing. The equilibrium water content and water loss showed that polymer micelle laden hydrogel with higher PAA/PEG concentration was in a higher swollen state. The dynamic viscoelastic properties howed that all polymer micelle laden hydrogels had some characteristics of crosslinked elastomers. The surface structure of freeze dried composite hydrogels was different from freeze dried pure hydrogel. The drug loading and releasing behaviors were detected to evaluate the drug loading and releasing capacity of hydrogels using orfloxacin and puerarin as model drugs. The results indicated the polymer micelle in hydrogel could hold or help to hold some ophthalmic drugs, and slow down orfloxacin release speed or keep puerarin stably stay for a time in hydrogels. In the end, it was found that the transparency of composite hydrogel became better after the hydrogel had been immersed in PBS for several weeks.


    CAONingning; YUYaoting; 等


    Cholesterol modified dextran(CHD) having self-aggrgation or self-assembly property was synthesized from cholesterol and 1,6-hexyldiisocyanate.The degree of substitution of cholesteryl moiety in dextran main line is 3-5 cholesterols the 100 glucose units.We have prepared water solution of CHD using probe type sonifier and N-Phenyl-a-naphthylamine(PNA) as a fluorescent probe to study CHD self-aggregate process.For each solution of two samples,we found that the maximum emission of PNA in CHD concentration.This change corresponds to the formation of micelle-like clusters self-aggregated by the cholesterol moiety once the CHD concentration.This change corresponds to the formation of micelle-like clusters self-aggregated by the cholesterol moiety once the CHD concentration exceeds 0.01mg/ml.

  11. Physico-chemical properties of meso-tetrakis(p-methoxyphenylporphyrin (TMPP incorporated into pluronicTM p-123 and f-127 polymeric micelles

    Bruno H. Vilsinski


    Full Text Available The physicochemical properties (solubilization, structural organization and stability of meso-tetrakis(p-methoxyphenylporphyrin (TMPP, a promising photosensitizer for photodynamic therapy, solubilized in polymeric micelles of tri-block copolymers PluronicTM P-123 and F-127, were studied. The formulations obtained by the solid dispersion method led to monomerization of TMPP in these copolymers. Solubility studies showed that P-123 solubilizes double the photosensitizer than F-127. The self-aggregation phenomenon was affected by the [TMPP]/[poloxamer] ratio and medium temperature. The decrease in the temperature of these systems promoted the formation of different kinds of TMPP aggregates intrinsically connected with the structural changes occurring in the micelles.

  12. Application of DPD in the design of polymeric nano-micelles as drug carriers.

    Ramezani, Mohammad; Shamsara, Jamal


    Developing new drug carrier systems are of a great importance in the treatment approach for a wide range of diseases. The simulation techniques can be valuable for decreasing the time and cost of developing novel drug carriers. Among the simulation methods there are a vast number of studies using dissipative particle dynamics (DPD) method for the prediction of different aspects of polymeric nano-micelles for encapsulating drugs. Here, we reviewed the results of the studies employing DPD for the simulation of drug loading and release in different polymeric micelles carriers. In some cases the simulation results were compared with the experimental results by the authors that were demonstrated the reliability of the DPD predictions.

  13. Complex coacervate core micelles with a lysozyme-modified corona.

    Danial, Maarten; Klok, Harm-Anton; Norde, Willem; Stuart, Martien A Cohen


    This paper describes the preparation, characterization, and enzymatic activity of complex coacervate core micelles (C3Ms) composed of poly(acrylic acid) (PAA) and poly(N-methyl-2-vinyl pyridinium iodide)-b-poly(ethylene oxide) (PQ2VP-PEO) to which the antibacterial enzyme lysozyme is end-attached. C3Ms were prepared by polyelectrolyte complex formation between PAA and mixtures containing different ratios of aldehyde and hydroxyl end-functionalized PQ2VP-PEO. This resulted in the formation of C3Ms containing 0-40% (w/w) of the aldehyde end-functionalized PQ2VP-PEO block copolymer (PQ2VP-PEO-CHO). Chemical conjugation of lysozyme was achieved via reductive amination of the aldehyde groups, which are exposed at the surface of the C3M, with the amine groups present in the side chains of the lysine residues of the protein. Dynamic and static light scattering indicated that the conjugation of lysozyme to C3Ms prepared using 10 and 20% (w/w) PQ2VP-PEO-CHO resulted in the formation of unimicellar particles. Multimicellar aggregates, in contrast, were obtained when lysozyme was conjugated to C3Ms prepared using 30 or 40% (w/w) PQ2VP-PEO-CHO. The enzymatic activity of the unimicellar lysozyme-C3M conjugates toward the hydrolysis of the bacterial substrate Micrococcus lysodeikticus was comparable to that of free lysozyme. For the multimicellar particles, in contrast, significantly reduced enzymatic rates of hydrolysis, altered circular dichroism, and red-shifted tryptophan fluorescence spectra were measured. These results are attributed to the occlusion of lysozyme in the interior of the multimicellar conjugates.

  14. 分子动力学模拟研究盐离子对十二烷基硫酸钠胶束溶液中亲水亲油协调机制的影响%Molecular Dynamics Simulation of Effect of Salt on the Compromise of Hydrophilic and Hydrophobic Interactions in Sodium Dodecyl Sulfate Micelle Solutions

    高健; 任瑛; 葛蔚


    The presence of salt has a profound effect on the size, shape and structure of sodium dodecyl sulfate (SDS) micelles. There have been a great number of experiments on SDS micelles in the presence and absence of salt to study this complex problem. Unfortunately, it is not clear yet how electrolyte ions influence the structure of micelles. By describing the compromise between dominant mechanisms, a simplified atomic model of SDS in presence of salt has been developed and the molecular dynamics (MD) simulations of two series of systems with different concentrations of salt and charges of ion have been performed. Polydispersity of micelle size is founded at relatively high concentration of SDS and low charge of cation. Although the counter-ion pairs with head groups are formed, the transition of micelle shape is not observed because the charge of cation is not enough to neutralize the polar of micelle surface.

  15. Ultrasonic transformation of micelle structures: effect of frequency and power.

    Yusof, Nor Saadah Mohd; Ashokkumar, Muthupandian


    A comprehensive investigation on the effect of ultrasonic frequency and power on the structural transformation of CTABr/NaSal micelles has been carried out. Sonication of this micelle system at various ultrasonic frequencies and power resulted in the formation and separation of two types of micelles. High viscoelastic threadlike micelles of ∼ 2 nm in diameter and several μm in length and tubular micelles possessing a viscosity slightly above that of water with ∼ 30-50 nm diameter and few hundred nm length. The structural transformation of micelles was induced by the shear forces generated during acoustic cavitation. At a fixed acoustic power of 40 W, the structural transformation was found to decrease from 211 to 647 kHz frequency due to the decreasing shear forces generated, as evidenced by rheological measurements and cryo-TEM images. At 355 kHz, an increase in the structural transformation was observed with an increase in acoustic power. These findings provide a knowledge base that could be useful for the manipulation of viscosity of micelles that may have applications in oil industry.

  16. Counter anion effect on the self-aggregation of dimethyl-di-N-octylammonium cation: a dual behavior between hydrotropes and surfactants.

    Collinet-Fressancourt, Marion; Leclercq, Loïc; Bauduin, Pierre; Aubry, Jean-Marie; Nardello-Rataj, Véronique


    Self-aggregation of eight dimethyl-di-N-octylammonium salts ([DiC(8)]) has been investigated as a function of the nature of the counteranion. Tensiometry, conductimetry, and [DiC(8)]-selective electrode measurements highlighted three different behaviors and led to a rationalization of the aggregation process depending on the counteranion: "hydrophilic" anions (MoO(4)(2-), WO(4)(2-), SO(4)(2-), F(-)) give only unimers and micelles, whereas less hydrated anions form unimers, dimers, and either one micelle-like structure (NO(3)(-), Br(-)) or two micelle-like structures (CH(3)SO(3)(-), Cl(-)). Small-angle neutron and dynamic light scattering confirms the unusual behavior of [DiC(8)][Cl], which forms two types of aggregates: (i) disk or vesicles between 10 and 30 mM and (ii) ellipsoidal micelles above 30 mM. For [DiC(8)][MoO(4)(2-)], the formation of ellipsoidal micelles is supported between 10 and 300 mM. Finally, shapes and sizes of the aggregates are confirmed by molecular dynamic experiments.

  17. Gemini阳离子表面活性剂的合成及其胶束生成 Gemini阳离子表面活性剂的合成及其胶束生成%Synthesis of Alkanediyl-α,ω-bis(Dimethyl Dodecylammonium Bromide) and their Micelle Formation in Aqueous Solutions

    游毅; 郑欧; 邱羽; 郑叶鸿; 赵剑曦; 韩国彬


    Cationic Gemini surfactants, alkanediyl-α,ω-bis(dimethyldodecylammonium bromide) have been synthesized by the following method: firstly dodecyl bromide was prepared by the reaction of dodecanol with bromic acid in the presence of strong sulfuric acid. Dodecylbromide was then reacted with N,N-tetramethyl ethane diamine(or N,N-tetramethyl hexana diamine) to prepare the title-compounds. Micellization of these Gemini surfactants was investigated using conductivity measurement. The results showed that the critical micelle concentration(cmc) of the Gemini surfactants has a much lower value compared with that of the corresponding “ monomer” . For a series of the Geminis with the same length(s) in the spacer chain, the cmc decreased with increasing the carbon number (m) in the alkyl chain. The aggregation number(N) of the micelle also drastically decreased with m. For the same value of m, the cmc varied slightly with s, which indicated that the electrostatic interaction between the ionic-groups of the “ monomer” has been naturally changed duo to a link between the two ionic-groups of the “ monomer” through a spacer. However, N was strongly decreased with s,which may be a reason of steric inhibition coming from the ionic-groups due to a link of spacer. With increasing temperature, micellization of the Gemini surfactants was slightly enhanced.

  18. Mesoscopic Simulation of Aggregates in Surfactant/Oil/Water Systems

    苑世领; 蔡政亭; 徐桂英


    The aggregates in sodium dedecylsulphate(SDS)/dimethylbenzene/water systems have been investigated using dissipative particles dynamic(DPD) simulation method.Through analyzing three-dimensional structures of aggregates,three simulated results are found.One is the phase separation,which is clearly observed by water density and the aggregates in the simulated cell;another is the water morphology in reverse micelle,which can be found through the isodensity slice of water including bound water,trapped water and bulky water;the third is about the water/oil interface,i.e.,ionic surfactant molecules,SDS,prefer to exist in the interface between water and oil phase at the low concentraion.

  19. Stereocomplex micelle from nonlinear enantiomeric copolymers efficiently transports antineoplastic drug

    Wang, Jixue; Shen, Kexin; Xu, Weiguo; Ding, Jianxun; Wang, Xiaoqing; Liu, Tongjun; Wang, Chunxi; Chen, Xuesi


    Nanoscale polymeric micelles have attracted more and more attention as a promising nanocarrier for controlled delivery of antineoplastic drugs. Herein, the doxorubicin (DOX)-loaded poly(D-lactide)-based micelle (PDM/DOX), poly(L-lactide)-based micelle (PLM/DOX), and stereocomplex micelle (SCM/DOX) from the equimolar mixture of the enantiomeric four-armed poly(ethylene glycol)-polylactide (PEG-PLA) copolymers were successfully fabricated. In phosphate-buffered saline (PBS) at pH 7.4, SCM/DOX exhibited the smallest hydrodynamic diameter ( D h) of 90 ± 4.2 nm and the slowest DOX release compared with PDM/DOX and PLM/DOX. Moreover, PDM/DOX, PLM/DOX, and SCM/DOX exhibited almost stable D hs of around 115, 105, and 90 nm at above normal physiological condition, respectively, which endowed them with great potential in controlled drug delivery. The intracellular DOX fluorescence intensity after the incubation with the laden micelles was different degrees weaker than that incubated with free DOX · HCl within 12 h, probably due to the slow DOX release from micelles. As the incubation time reached to 24 h, all the cells incubated with the laden micelles, especially SCM/DOX, demonstrated a stronger intracellular DOX fluorescence intensity than free DOX · HCl-cultured ones. More importantly, all the DOX-loaded micelles, especially SCM/DOX, exhibited potent antineoplastic efficacy in vitro, excellent serum albumin-tolerance stability, and satisfactory hemocompatibility. These encouraging data indicated that the loading micelles from nonlinear enantiomeric copolymers, especially SCM/DOX, might be promising in clinical systemic chemotherapy through intravenous injection.

  20. Aggregation Behavior of Long-Chain Piperidinium Ionic Liquids in Ethylammonium Nitrate

    Caili Dai


    Full Text Available Micelles formed by the long-chain piperidinium ionic liquids (ILs N-alkyl-N-methylpiperidinium bromide of general formula CnPDB (n = 12, 14, 16 in ethylammonium nitrate (EAN were investigated through surface tension and dissipative particle dynamics (DPD simulations. Through surface tension measurements, the critical micelle concentration (cmc, the effectiveness of surface tension reduction (Πcmc, the maximum excess surface concentration (Гmax and the minimum area occupied per surfactant molecule (Amin can be obtained. A series of thermodynamic parameters (DG0 m, DH0 m and DS0 m of micellization can be calculated and the results showed that the micellization was entropy-driven. In addition, the DPD simulation was performed to simulate the whole aggregation process behavior to better reveal the micelle formation process.

  1. Novel Pyridinium Surfactants with Unsaturated Alkyl Chains : Aggregation Behavior and Interactions with Methyl Orange in Aqueous Solution

    Kuiper, Johanna M.; Buwalda, Rixt T.; Hulst, Ron; Engberts, Jan B.F.N.


    This paper presents the synthesis and a study of the aggregation behavior of 4-undecyl-1-methyl- and 4-undecenyl-1-methylpyridinium iodide surfactants. The effect of the position of the double bond in the alkyl chain of the surfactant on the critical micelle concentration (cmc), degree of counterion

  2. Self-assembly of micelles into designed networks

    Pyatenko Alexander


    Full Text Available AbstractThe EO20PO70EO20(molecular weight 5800 amphiphile as a template is to form dispersed micelle structures. Silver nanoparticles, as inorganic precursors synthesized by a laser ablation method in pure water, are able to produce the highly ordered vesicles detected by TEM micrography. The thickness of the outer layer of a micelle, formed by the silver nanoparticles interacting preferentially with the more hydrophilic EO20block, was around 3.5 nm. The vesicular structure ensembled from micelles is due to proceeding to the mixture of cubic and hexagonal phases.

  3. Pressure-induced structural transition of nonionic micelles

    V K Aswal; R Vavrin; J Kohlbrecher; A G Wagh


    We report dynamic light scattering and small angle neutron scattering studies of the pressure-induced structural transition of nonionic micelles of surfactant polyoxyethylene 10 lauryl ether (C12E10) in the pressure range 0 to 2000 bar. Measurements have been performed on 1 wt% C12E10 in aqueous solution with and without the addition of KF. Micelles undergo sphere to lamellar structural transitions as the pressure is increased. On addition of KF, rod-like micelles exist at ambient pressure, which results in rod-like to lamellar structural transition at a much lower pressure in the presence of KF. Micellar structural transitions have been observed to be reversible.

  4. Polyion complex micelles from plasmid DNA and poly(ethylene glycol)-poly(L-lysine) block copolymer as serum-tolerable polyplex system: physicochemical properties of micelles relevant to gene transfection efficiency.

    Itaka, Keiji; Yamauchi, Kyosuke; Harada, Atsushi; Nakamura, Kozo; Kawaguchi, Hiroshi; Kataoka, Kazunori


    Polyion complex (PIC) micelles composed of the poly(ethylene glycol)-poly(L-lysine) (PEG-PLL) block copolymer and plasmid DNA (pDNA) were investigated in this study from a physicochemical viewpoint to get insight into the structural feature of the PIC micellar vector system to show practical gene transfection efficacy particularly under serum-containing medium. The residual ratio (r) of the lysine units in PEG-PLL to the phosphate units of pDNA in the system significantly affects the size of the PIC micelles evaluated from dynamic light scattering, being decreased from approximately 120 to 80 nm with an increase in the r value for the region with r > or = 1.0. The zeta potential of the complexes slightly increased with r in the same region, yet maintained a very small absolute value and leveled off to a few mV at r approximately 2.0. These results suggest that the micelles are most likely to take the core-shell structure with dense PEG palisades surrounding the PIC core to compartmentalize the condensed pDNA. Furthermore, an increasing r value in the region of r > or = 1 induces a rearrangement of the stoichiometric complex formed at r=1.0 to the non-stoichiometric complex composed of the excess block copolymer. The association number of pDNA and the block copolymer in the micelle was estimated from the apparent micellar molecular weight determined by static light scattering measurements, indicating that a single pDNA molecule was incorporated in each of the micelles prepared from the PEG (Mw=12,000 g/mol)-PLL (polymerization degree of PLL segment: 48) (12-48) block copolymer at r=2.0. These 12-48/pDNA micelles showed a gene expression comparable to the lipofection toward cultured 293 cells, though 100 microM chloroquine was required in the transfection medium. Notably, even in the presence of serum, the PIC micelles achieved appreciable cellular association to attain a high gene expression, which is in sharp contrast with the drastic decrease in the gene

  5. Hydrophobically modified polyelectrolytes: Characterization, aggregation and adsorption

    Islam, Mohammad Ferdous

    The focus of our work was to experimentally study the aggregation and adsorption behavior of model HM polyelectrolytes. Hydrophobically modified alkali soluble emulsions (HASE), the model HM polyelectrolytes, were chosen because they had complex architecture yet possessed key variables for systematic study. The HASE polymers have methacrylic acid (MAA) and ethyl acrylate (EA) in the backbone with pendent hydrophobic groups. Characterization of a single molecule is an important first step in understanding the aggregation and adsorption of these polymers. However, characterizations of the HASE polymers using conventional techniques such as gel permeation chromatography or static light scattering were difficult because of the hydrophobic association. In this study, two different approaches have been taken to prevent the hydrophobic association in aqueous solution: (1) hydrolyze the polymer to cleave the hydrophobic constituents, and (2) use methyl beta-cyclodextrin that has a hydrophobic cavity and a hydrophilic outer shell, to shield the hydrophobes from associating. By taking these two approaches and using gel permeation chromatography (GPC), dynamic (DLS) and static (SLS) light scattering techniques, the molecular weight, hydrodynamic radius and radius of gyration of a single molecule were determined. Except for one chemical site, we were able to determine that branching or grafting did not occur in the polymer chain during synthesis. Our aggregation studies showed that, in aqueous solutions, the HASE polymers formed small aggregates (presumably single micelles of single or a few chains) and large aggregates (presumably formed by bridging between micelles). The radii and masses of the larger aggregates, measured using DLS and SLS, were found to increase with an increase in the polymer concentration, indicating an open association process for the HASE polymers. Our SLS results also showed that, at high salt concentration, the aggregates of the HASE polymer with

  6. Anion Exchange on Cationic Surfactant Micelles, and a Speciation Model for Estimating Anion Removal on Micelles during Ultrafiltration of Water.

    Chen, Ming; Jafvert, Chad T


    Surfactant micelles combined with ultrafiltration can partially, or sometimes nearly completely, separate various ionic and nonionic pollutants from water. To this end, the selectivity of aqueous micelles composed of either cetyltrimethylammonium (CTA(+)) bromide or cetylpyridinium (CP(+)) chloride toward many environmentally relevant anions (IO3(-), F(-), Cl(-), HCO3(-), NO2(-), Br(-), NO3(-), H2PO4(-), HPO4(2-), SO4(2-), and CrO4(2-)) was investigated. Selectivity coefficients of CTA(+) micelles (with respect to Br(-)) and CP(+) micelle (with respect to Cl(-)) for these anions were evaluated using a simple thermodynamic ion exchange model. The sequence of anion affinity for the CTA(+) micelles and for the CP(+) micelles were the same, with decreasing affinity occurring in the order of: CrO4(2-) > SO4(2-) > HPO4(2-) > NO3(-) > Br(-) > NO2(-) > Cl(-) > HCO3(-) > H2PO4(-) ≈ F(-). From the associated component mass balance and ion exchange (i.e., mass action) equations, an overall speciation model was developed to predict the distribution of all anions between the aqueous and micellar pseudophase for complex ionic mixtures. Experimental results of both artificial and real surface waters were in good agreement to model predictions. Further, the results indicated that micelles combined with ultrafiltration may be a potential technology for nutrient and other pollutant removal from natural or effluent waters.

  7. Iron oxide nanoparticle-micelles (ION-micelles for sensitive (molecular magnetic particle imaging and magnetic resonance imaging.

    Lucas W E Starmans

    Full Text Available BACKGROUND: Iron oxide nanoparticles (IONs are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI. METHODS AND RESULTS: IONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles. Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles bound to blood clots. CONCLUSIONS: The presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular MPI and warrants further investigation of the FibPep-ION-Micelle

  8. Photophysical study of a charge transfer oxazole dye in micelles: Role of surfactant headgroups

    Maiti, Jyotirmay [Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126 (India); Sarkar, Yeasmin; Parui, Partha Pratim [Department of Chemistry, Jadavpur University, Kolkata 700032 (India); Chakraborty, Sandipan [Department of Microbiology, University of Calcutta, Kolkata 700019 (India); Biswas, Suman [Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126 (India); Das, Ranjan, E-mail: [Department of Chemistry, West Bengal State University, Barasat, Kolkata 700126 (India)


    Photophysics of 5-(4′′-dimethylaminophenyl)-2-(4′-sulfophenyl)oxazole, sodium salt (DMO) which undergoes intramolecular charge transfer in the excited state was studied in micelles. In the cationic and the nonionic micelles, significantly higher fluorescence quantum yield is observed in comparison to the anionic micelles, due to much lower accessibility of DMO to the water molecules in the former micelles than the latter. Time-resolved fluorescence decays were characterized by a fast (τ{sub 1}) and a slow (τ{sub 2}) component of decay in all the micelles. The fast decay component (τ{sub 1}) increases significantly in going from the anionic micelles to the cationic micelles, because of the poorly hydrated headgroup region of the latter micelles compared to the former. Furthermore, much higher value of the slow component of decay (τ{sub 2}) is observed for the cationic and the neutral micelles than the anionic micelles. This is attributed to the increased penetration of water molecules into the micellar core of the anionic micelles compared to the cationic and the neutral micelles. - Highlights: • Photophysics of the fluorophore are remarkably different in the cationic and the anionic micelles. • Differential hydration of the surfactant headgroups gives rise to significantly different fluorescence quantum yield and lifetime in oppositely charged micelles. • Electrostatic interactions fine tune location of the fluorophore in the micelle–water interface of ionic micelles.

  9. In vivo pharmacokinetics, biodistribution and antitumor effect of amphiphilic poly(L-amino acids) micelles loaded with a novel all-trans retinoic acid derivative.

    Tang, Jihui; Wang, Xinqun; Wang, Ting; Chen, Feihu; Zhou, Jianping


    Poly(amino acid)s are well-known as biodegradable and environmentally acceptable materials. In this study, a series of poly(L-aspartic acid)-b-poly(L-phenylalanine) (PAA-PPA) compounds with different degrees of polymerization were used to prepare copolymer micelles for a poorly water-soluble drug 4-amino-2-trifluoromethyl-phenyl retinate (ATPR, a novel all-trans retinoic acid derivative) and in vivo pharmacokinetics, biodistribution and antitumor efficacy of ATPR delivered by PAA-PPA micelles were evaluated. The area under the plasma concentration time curve AUC0→∞ of ATPR-loaded PAA20PPA20 micelles was 2.23 and 1.97 times higher than that of ATPR solution and ATPR CrmEL solution, respectively; In addition, the mean residence time (MRT) was increased 1.67 and 1.97-fold, respectively and the total body clearance (CL) was reduced 2.25 and 1.98-fold, respectively. The biodistribution study indicated that most of the ATPR in the ATPR-M group was distributed in the liver and there was delayed liver aggregation compared with the ATPR solution and ATPR CrmEL solution groups. Furthermore, the antitumor efficacy of ATPR-loaded PAA20PPA20 micelles was demonstrated in in vivo antitumor models involving mice inoculated with the human gastric cancer cell line SGC-7901. At the same dose of 7mg/kg, the ATPR-loaded micelles group demonstrated a better tumor growth inhibition and induced differentiation than the groups given ATPR solution and ATPR CrmEL solution. Therefore, the ATPR-loaded PAA-PPA micelles appear to be a potentially useful drug delivery system for ATPR and suitable for the chemotherapy of gastric cancer.

  10. Polydispersity-Driven Block Copolymer Amphiphile Self-Assembly into Prolate-Spheroid Micelles

    Schmitt, Andrew L.; Repollet-Pedrosa, Milton H.; Mahanthappa, Mahesh K. (UW)


    The aqueous self-assembly behavior of polydisperse poly(ethylene oxide-b-1,4-butadiene-b-ethylene oxide) (OBO) macromolecular triblock amphiphiles is examined to discern the implications of continuous polydispersity in the hydrophobic block on the resulting aqueous micellar morphologies of otherwise monodisperse polymer surfactants. The chain length polydispersity and implicit composition polydispersity of these samples furnishes a distribution of preferred interfacial curvatures, resulting in dilute aqueous block copolymer dispersions exhibiting coexisting spherical and rod-like micelles with vesicles in a single sample with a O weight fraction, w{sub O}, of 0.18. At higher w{sub O} = 0.51-0.68, the peak in the interfacial curvature distribution shifts and we observe the formation of only American football-shaped micelles. We rationalize the formation of these anisotropically shaped aggregates based on the intrinsic distribution of preferred curvatures adopted by the polydisperse copolymer amphiphiles and on the relief of core block chain stretching by chain-length-dependent intramicellar segregation.

  11. Determination of micelle formation of ketorolac tromethamine in aqueous media by acoustic measurements

    Savaroglu, Gokhan, E-mail: [Eskisehir Osmangazi University, Department of Physics, 26480 Eskisehir (Turkey); Genc, Luetfi [Anadolu University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 26470 Eskisehir (Turkey)


    Graphical abstract: Value of critical micelle concentration (CMC) were detected by speed of sound and determined by an analytical method based on the Phillips definition of the CMC. Highlights: Black-Right-Pointing-Pointer The aim of this study was to investigate the aggregation behaviour of KT. Black-Right-Pointing-Pointer Influence of KT concentration and temperature upon volumetric properties was studied. Black-Right-Pointing-Pointer CMC of KT aqueous solution was determined by using speeds of sound measurements. - Abstract: Density and speed of sound of ketorolac tromethamine in aqueous solutions have been measured as a function of concentration at atmospheric pressure and in the temperature range from 293.15 to 313.15 K. Apparent molar volumes, apparent isentropic compressibility and isentropic compressibility values have also been calculated from the experimental density and speed of sound data. Partial molar volume and partial molar isentropic compressibility are obtained from fitting procedures the data on apparent molar volume, V{sub {phi}}, and apparent isentropic compressibility, K{sub {phi}(S)}. Partial molar volume, V{sub {phi}}{sup 0}, and partial molar isentropic compressibility, k{sub {phi}(S)}{sup 0}, are informative thermodynamic characteristics that reflect solute hydration. The critical micelle concentration (CMC) was determined from speed of sound data by an analytical method based on the Phillips definition of the CMC. Using these results, it was possible to establish the solvent-drug interactions.

  12. PEE-PEO block copolymer exchange rate between micelles is detergent and temperature activated

    Schantz, Allen; Saboe, Patrick; Lee, Hee-Young; Sines, Ian; Butler, Paul; Bishop, Kyle; Maranas, Janna; Kumar, Manish

    We examine the kinetics of polymer chain exchange between polymer/detergent micelles, a system relevant to the synthesis of protein-containing biomimetic membranes. Although chain exchange between polymer aggregates in water is too slow to observe, adding detergent allows us to determine chain exchange rates using time-resolved small-angle neutron scattering (TR-SANS). We examine a membrane-protein-relevant, vesicle-forming ultra-short polymer, Poly(ethyl ethylene)20-Poly(ethylene oxide)18 (PEE20-PEO18). PEE20-PEO18 is solubilized in mixed micelles with the membrane-protein-compatible non-ionic detergent octyl- β -D-glucoside (OG). We show that OG activates block copolymer exchange, and obtain rate constants at two detergent concentrations above the CMC (critical micellar concentration) of OG. We find that chain exchange increases two orders of magnitude when temperature increases from 308 to 338 K, and that even a 1 mg/mL increase in OG concentration leads to a noticeable increase in exchange rate. We also calculate the activation energy for chain exchange and find that it is much higher than for lipid exchange. These findings explain the need for high detergent concentration and/or temperature to synthesize densely packed polymer/protein membranes.

  13. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

    Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo


    Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

  14. High-resolution NMR structure of the antimicrobial peptide protegrin-2 in the presence of DPC micelles

    Usachev, K. S., E-mail:; Efimov, S. V.; Kolosova, O. A.; Filippov, A. V.; Klochkov, V. V. [Kazan Federal University (Russian Federation)


    PG-1 adopts a dimeric structure in dodecylphosphocholine (DPC) micelles, and a channel is formed by the association of several dimers but the molecular mechanisms of the membrane damage by non-α-helical peptides are still unknown. The formation of the PG-1 dimer is important for pore formation in the lipid bilayer, since the dimer can be regarded as the primary unit for assembly into the ordered aggregates. It was supposed that only 12 residues (RGGRL-CYCRR-RFCVC-V) are needed to endow protegrin molecules with strong antibacterial activity and that at least four additional residues are needed to add potent antifungal properties. Thus, the 16-residue protegrin (PG-2) represents the minimal structure needed for broad-spectrum antimicrobial activity encompassing bacteria and fungi. As the peptide conformation and peptide-to-membrane binding properties are very sensitive to single amino acid substitutions, the solution structure of PG-2 in solution and in a membrane mimicking environment are crucial. In order to find evidence if the oligomerization state of PG-1 in a lipid environment will be the same or not for another protegrins, we investigate in the present work the PG-2 NMR solution structure in the presence of perdeuterated DPC micelles. The NMR study reported in the present work indicates that PG-2 form a well-defined structure (PDB: 2MUH) composed of a two-stranded antiparallel β-sheet when it binds to DPC micelles.

  15. Effect of double quaternary ammonium groups on micelle formation of partially fluorinated surfactant.

    Matsuoka, Keisuke; Chiba, Nagisa; Yoshimura, Tomokazu; Takeuchi, Emi


    To investigate the effect of divalency on the micelle properties, we synthesized divalent cationic surfactants composed of fluorocarbons and double quaternary ammonium groups N,N-dimethyl-N-[2-(N'-trimethylammonium)ethyl]-1-(3-perfluoroalkyl-2-hydroxypropyl) ammonium bromide [C(n)(F)C(3)-2Am; where n (=8 or 10) represents the number of carbon atoms in the fluorocarbon chain]. The double quaternary ammonium groups are continuously combined by the ethylene spacer in the surfactant head group, which clearly distinguishes the molecular design of the surfactant from those of the other typical divalent surfactants, bolaform and gemini types. The presence of the divalent head group results in an advantageous increase in their solubility [i.e., rise in the critical micelle concentration (cmc)]; however, the extra electrostatic repulsion between divalent cations decreases the surface activity in comparison with monovalent homologous fluorinated surfactants. The cmc, surface tension at cmc, and area occupied by a surfactant molecule in aqueous solution at 298.2K are 4.32 mM, 30.6 mN m(-1), and 0.648 nm(2 )molecule(-1), respectively, for C(8)(F)C(3)-2Am, and 1.51 mM, 30.4 mN m(-1), and 0.817 nm(2) molecule(-1), respectively, for C(10)(F)C(3)-2Am. The micellar size and shape were investigated by dynamic light scattering and freeze-fracture transmission electron microscopy (TEM). The TEM micrographs show that C(n)(F)C(3)-2Am (n=8 and 10) mainly forms ellipsoidal micelles approximately 10-100 nm in size for n=8 and approximately 10-20 nm in size for n=10. The degree of counterion binding to micelle was determined by selective electrode potential measurements, and the results of 0.7-0.8 agree with the average values for conventional monovalent ionic surfactants.

  16. Encapsulation into complex coacervate core micelles promotes EGFP dimerization

    Nolles, A.; Dongen, Van N.J.E.; Westphal, A.H.; Visser, A.J.W.G.; Kleijn, J.M.; Berkel, Van W.J.H.; Borst, J.W.


    Complex coacervate core micelles (C3Ms) are colloidal structures useful for encapsulation of biomacromolecules. We previously demonstrated that enhanced green fluorescent protein (EGFP) can be encapsulated into C3Ms using the diblock copolymer

  17. Enantiomer separation by ultrafiltration of enantioselective micelles in multistage systems

    Overdevest, P.E.M.


    The Food and Bioprocess Engineering Group of Wageningen University, The Netherlands, is developing a new enantiomer separation system that is based on ultrafiltration (UF) of enantioselective micelles containing chiral selector molecules. Enantiomer molecules are optical isomers (mirror images), and

  18. Rheology and phase behavior of dense casein micelle dispersions

    Bouchoux, A.; Debbou, B.; Gésan-Guiziou, G.; Famelart, M.-H.; Doublier, J.-L.; Cabane, B.


    Casein micelle dispersions have been concentrated through osmotic stress and examined through rheological experiments. In conditions where the casein micelles are separated from each other, i.e., below random-close packing, the dispersions have exactly the flow and dynamic properties of the polydisperse hard-sphere fluid, demonstrating that the micelles interact only through excluded volume effects in this regime. These interactions cause the viscosity and the elastic modulus to increase by three orders of magnitude approaching the concentration of random-close packing estimated at Cmax≈178 g/l. Above Cmax, the dispersions progressively turn into "gels" (i.e., soft solids) as C increases, with elastic moduli G' that are nearly frequency independent. In this second regime, the micelles deform and/or deswell as C increases, and the resistance to deformation results from the formation of bonds between micelles combined with the intrinsic mechanical resistance of the micelles. The variation in G' with C is then very similar to that observed with concentrated emulsions where the resistance to deformation originates from a set of membranes that separate the droplets. As in the case of emulsions, the G' values at high frequency are also nearly identical to the osmotic pressures required to compress the casein dispersions. The rheology of sodium caseinate dispersions in which the caseins are not structured into micelles is also reported. Such dispersions have the behavior of associative polymer solutions at all the concentrations investigated, further confirming the importance of structure in determining the rheological properties of casein micelle systems.

  19. Effects of copolymer component on the properties of phosphorylcholine micelles

    Wu Z


    Full Text Available Zhengzhong Wu,1 Mengtan Cai,1 Jun Cao,2 Jiaxing Zhang,1 Xianglin Luo1,3 1College of Polymer Science and Engineering, 2National Engineering Research Center for Biomaterials, 3State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, People’s Republic of China Abstract: Zwitterionic polymers have unique features, such as good compatibility, and show promise in the application of drug delivery. In this study, the zwitterionic copolymers, poly(ε-caprolactone-b-poly(2-methacryloyloxyethyl phosphorylcholine with disulfide (PCL-ss-PMPC or poly(ε-caprolactone-b-poly(2-methacryloyloxyethyl phosphorylcholine or without disulfide (PCL-PMPC and with different block lengths in PCL-ss-PMPC, were designed. The designed copolymers were obtained by a combination of ring-opening polymerization and atom transferring radical polymerization. The crystallization properties of these polymers were investigated. The micelles were prepared based on the obtained copolymers with zwitterionic phosphorylcholine as the hydrophilic shell and PCL as the hydrophobic core. The size distributions of the blank micelles and the doxorubicin (DOX-loaded micelles were uniform, and the micelle diameters were <100 nm. In vitro drug release and intracellular drug release results showed that DOX-loaded PCL-ss-PMPC micelles could release drugs faster responding to the reduction condition and the intracellular microenvironment in contrast to PCL-PMPC micelles. Moreover, in vitro cytotoxicity evaluation revealed that the designed copolymers possessed low cell toxicity, and the inhibiting effect of DOX-loaded phosphorylcholine micelles to tumor cells was related to the components of these copolymers. These results reveal that the reduction-responsive phosphorylcholine micelles with a suitable ratio of hydrophilic/hydrophobic units can serve as promising drug carriers. Keywords: zwitterionic, reduction-sensitive, disulfide, phosphorylcholine

  20. Self-Assembly of Amphiphilic Block Copolypeptoids – Micelles, Worms and Polymersomes

    Fetsch, Corinna; Gaitzsch, Jens; Messager, Lea; Battaglia, Giuseppe; Luxenhofer, Robert


    Polypeptoids are an old but recently rediscovered polymer class with interesting synthetic, physico-chemical and biological characteristics. Here, we introduce new aromatic monomers, N-benzyl glycine N-carboxyanhydride and N-phenethyl glycine N-carboxyanhydride and their block copolymers with the hydrophilic polysarcosine. We compare their self-assembly in water and aqueous buffer with the self-assembly of amphiphilic block copolypeptoids with aliphatic side chains. The aggregates in water were investigated by dynamic light scattering and electron microscopy. We found a variety of morphologies, which were influenced by the polymer structure as well as by the preparation method. Overall, we found polymersomes, worm-like micelles and oligo-lamellar morphologies as well as some less defined aggregates of interconnected worms and vesicles. Such, this contribution may serve as a starting point for a more detailed investigation of the self-assembly behavior of the rich class of polypeptoids and for a better understanding between the differences in the aggregation behavior of non-uniform polypeptoids and uniform peptoids. PMID:27666081

  1. Structure and stability of complex coacervate core micelles with lysozyme.

    Lindhoud, Saskia; Vries, Renko de; Norde, Willem; Stuart, Martien A Cohen


    Encapsulation of enzymes by polymers is a promising method to influence their activity and stability. Here, we explore the use of complex coacervate core micelles for encapsulation of enzymes. The core of the micelles consists of negatively charged blocks of the diblock copolymer PAA42PAAm417 and the positively charged homopolymer PDMAEMA150. For encapsulation, part of the positively charged homopolymer was replaced by the positively charged globular protein lysozyme. We have studied the formation, structure, and stability of the resulting micelles for three different mixing ratios of homopolymer and lysozyme: a system predominantly consisting of homopolymer, a system predominantly consisting of lysozyme, and a system where the molar ratio between the two positively charged molecules was almost one. We also studied complexes made of only lysozyme and PAA42PAAm417. Complex formation and the salt-induced disintegration of the complexes were studied using dynamic light-scattering titrations. Small-angle neutron scattering was used to investigate the structures of the cores. We found that micelles predominantly consisting of homopolymer are spherical but that complex coacervate core micelles predominantly consisting of lysozyme are nonspherical. The stability of the micelles containing a larger fraction of lysozyme is lower.

  2. Microemulsions and Aggregation Formation in Extraction Processes for Used Nuclear Fuel: Thermodynamic and Structural Studies

    Nilsson, Mikael [Univ. of California, Irvine, CA (United States)


    Advanced nuclear fuel cycles rely on successful chemical separation of various elements in the used fuel. Numerous solvent extraction (SX) processes have been developed for the recovery and purification of metal ions from this used material. However, the predictability of process operations has been challenged by the lack of a fundamental understanding of the chemical interactions in several of these separation systems. For example, gaps in the thermodynamic description of the mechanism and the complexes formed will make predictions very challenging. Recent studies of certain extraction systems under development and a number of more established SX processes have suggested that aggregate formation in the organic phase results in a transformation of its selectivity and efficiency. Aggregation phenomena have consistently been interfering in SX process development, and have, over the years, become synonymous with an undesirable effect that must be prevented. This multiyear, multicollaborative research effort was carried out to study solvation and self-organization in non-aqueous solutions at conditions promoting aggregation phenomena. Our approach to this challenging topic was to investigate extraction systems comprising more than one extraction reagent where synergy of the metal ion could be observed. These systems were probed for the existence of stable microemulsions in the organic phase, and a number of high-end characterization tools were employed to elucidate the role of the aggregates in metal ion extraction. The ultimate goal was to find connections between synergy of metal ion extraction and reverse micellar formation. Our main accomplishment for this project was the expansion of the understanding of metal ion complexation in the extraction system combining tributyl phosphate (TBP) and dibutyl phosphoric acid (HDBP). We have found that for this system no direct correlation exists for the metal ion extraction and the formation of aggregates, meaning that the

  3. Structuration in the Interface of Direct and Reversed Micelles of Sucrose Esters, Studied by Fluorescent Techniques

    Sandoval, Catalina; Ortega, Anakenna; Sanchez, Susana A.; Morales, Javier; Gunther, German


    Background Reactors found in nature can be described as micro-heterogeneous systems, where media involved in each micro-environment can behave in a markedly different way compared with the properties of the bulk solution. The presence of water molecules in micro-organized assemblies is of paramount importance for many chemical processes, ranging from biology to environmental science. Self-organized molecular assembled systems are frequently used to study dynamics of water molecules because are the simplest models mimicking biological membranes. The hydrogen bonds between sucrose and water molecules are described to be stronger (or more extensive) than the ones between water molecules themselves. In this work, we studied the capability of sucrose moiety, attached to alkyl chains of different length, as a surface blocking agent at the water-interface and we compared its properties with those of polyethylenglycol, a well-known agent used for this purposes. Published studies in this topic mainly refer to the micellization process and the stability of mixed surfactant systems using glycosides. We are interested in the effect induced by the presence of sucrose monoesters at the interface (direct and reverse micelles) and at the palisade (mixtures with Triton X-100). We believe that the different functional group (ester), the position of alkyl chain (6-O) and the huge capability of sucrose to interact with water will dramatically change the water structuration at the interface and at the palisade, generating new possibilities for technological applications of these systems. Results Our time resolved and steady state fluorescence experiments in pure SEs micelles show that sucrose moieties are able to interact with a high number of water molecules promoting water structuration and increased viscosity. These results also indicate that the barrier formed by sucrose moieties on the surface of pure micelles is more effective than the polyoxyethylene palisade of Triton X-100

  4. Structuration in the interface of direct and reversed micelles of sucrose esters, studied by fluorescent techniques.

    Catalina Sandoval

    Full Text Available Reactors found in nature can be described as micro-heterogeneous systems, where media involved in each micro-environment can behave in a markedly different way compared with the properties of the bulk solution. The presence of water molecules in micro-organized assemblies is of paramount importance for many chemical processes, ranging from biology to environmental science. Self-organized molecular assembled systems are frequently used to study dynamics of water molecules because are the simplest models mimicking biological membranes. The hydrogen bonds between sucrose and water molecules are described to be stronger (or more extensive than the ones between water molecules themselves. In this work, we studied the capability of sucrose moiety, attached to alkyl chains of different length, as a surface blocking agent at the water-interface and we compared its properties with those of polyethylenglycol, a well-known agent used for this purposes. Published studies in this topic mainly refer to the micellization process and the stability of mixed surfactant systems using glycosides. We are interested in the effect induced by the presence of sucrose monoesters at the interface (direct and reverse micelles and at the palisade (mixtures with Triton X-100. We believe that the different functional group (ester, the position of alkyl chain (6-O and the huge capability of sucrose to interact with water will dramatically change the water structuration at the interface and at the palisade, generating new possibilities for technological applications of these systems.Our time resolved and steady state fluorescence experiments in pure SEs micelles show that sucrose moieties are able to interact with a high number of water molecules promoting water structuration and increased viscosity. These results also indicate that the barrier formed by sucrose moieties on the surface of pure micelles is more effective than the polyoxyethylene palisade of Triton X-100. The

  5. Balancing energy flexibilities through aggregation

    Valsomatzis, Emmanouil; Hose, Katja; Pedersen, Torben Bach


    One of the main goals of recent developments in the Smart Grid area is to increase the use of renewable energy sources. These sources are characterized by energy fluctuations that might lead to energy imbalances and congestions in the electricity grid. Exploiting inherent flexibilities, which exist...... in both energy production and consumption, is the key to solving these problems. Flexibilities can be expressed as flex-offers, which due to their high number need to be aggregated to reduce the complexity of energy scheduling. In this paper, we discuss balance aggregation techniques that already during...

  6. Aggregation kinetics of a simulated telechelic polymer

    Wilson, Mark; Rabinovitch, Avinoam; Baljon, Arlette R. C.


    We investigate the aggregation kinetics of a simulated telechelic polymer gel. In the hybrid molecular dynamics (MD)/Monte Carlo (MC) algorithm, aggregates of associating end groups form and break according to MC rules, while the position of the polymers in space is dictated by MD. As a result, the aggregate sizes change over time. In order to describe this aggregation process, we employ master equations. They define changes in the number of aggregates of a certain size in terms of reaction rates. These reaction rates indicate the likelihood that two aggregates combine to form a large one, or that a large aggregate splits into two smaller parts. The reaction rates are obtained from the simulations for a range of temperatures. Our results indicate that the rates are not only temperature dependent, but also a function of the sizes of the aggregates involved in the reaction. Using the measured rates, solutions to the master equations are shown to be stable and in agreement with the aggregate size distribution, as obtained directly from simulation data. Furthermore, we show how temperature-induced variations in these rates give rise to the observed changes in the aggregate distribution that characterizes the sol-gel transition.

  7. A vertically resolved model for phytoplankton aggregation

    Iris Kriest; Geoffrey T Evans


    This work presents models of the vertical distribution and flux of phytoplankton aggregates, including changes with time in the distribution of aggregate sizes and sinking speeds. The distribution of sizes is described by two parameters, the mass and number of aggregates, which greatly reduces the computational cost of the models. Simple experiments demonstrate the effects of aggregation on the timing and depth distribution of primary production and export. A more detailed ecological model is applied to sites in the Arabian Sea; it demonstrates that aggregation can be important for deep sedimentation even when its effect on surface concentrations is small, and it presents the difference in timing between settlement of aggregates and fecal pellets.

  8. Self-assembly and supramolecular liquid crystals based on organic cation encapsulated polyoxometalate hybrid reverse micelles and pyridine derivatives.

    Yin, Shengyan; Sun, Hang; Yan, Yi; Zhang, Hui; Li, Wen; Wu, Lixin


    The controlled self-assembly of multi-components in one system represents the capability integrating intermolecular interactions and functions of components and is believed the key procedure leading to multifunctional materials finally. In pursuing this goal, we used a double-chain cationic surfactant with a benzoic acid group at the end of one tail to encapsulate Keggin-type polyanion clusters via electrostatic interaction, obtaining uniform supramolecular hybrid reverse micelles, which served as hydrogen-bonding donors. Five pyridine derivatives containing conjugated and non-conjugated groups were chosen as hydrogen-bonding acceptors to bind with reverse micelles. Through mixing with these components according to chemical stoichiometry, the hybrid reverse micelle changed to a new self-assembly precursor through intermolecular hydrogen bonding. The as-prepared reverse micelles bearing conjugated pyridine groups exhibit supramolecular liquid crystal properties, which were characterized by differential scanning calorimetry, polarizing optical microscopy, and X-ray diffraction. The length and number of the alky chain in the pyridine derivatives, as well as the charges of polyoxometalates were also studied with regard to the liquid crystal structure. The synergistic effect of among three components was analyzed, and the liquid crystal properties could be conveniently adjusted through the modification of the hydrogen-bonding acceptor components.

  9. Interaction of quinine sulfate with anionic micelles of sodium dodecylsulfate: A time-resolved fluorescence spectroscopy at different pH

    Joshi, Sunita; Pant, Debi D.


    Photophysical behavior and rotational relaxation dynamics of quinine sulfate (QS) in anionic surfactant, sodium dodecylsulfate (SDS) at different pH have been studied using steady state and time resolved fluorescence spectroscopy. It has been observed that the cationic form of quinine sulfate (at pH 2) forms a fluorescent ion pair complex with the surfactant molecules at lower concentrations of surfactant. However, for higher concentrations of SDS, the probe molecules bind strongly with the micelles and reside at the water-micelle interface. At pH 7, QS is singly protonated in bulk aqueous solution. At lower concentrations of SDS aggregation between probe and surfactant molecules has been observed. However, for higher concentrations of SDS, an additional fluorescence peak corresponding to dicationic form of QS appears and this has been attributed to double protonation of the QS molecule in micellar solution. At pH 7, in the presence of SDS micelles, the photophysical properties of QS showed substantial changes compared to that in the bulk water solution. At pH 12, an increase in fluorescence intensity and lifetime has been observed and this has been attributed to the increase in radiative rate due to the incorporation of QS at the micelle-water interface. The local pH at micellar surface has been found different from the pH of bulk solution.

  10. 酪蛋白胶束结构研究方法综述%A review on the studying means of casein micelle structure

    史莹; 杨敏; 梁琪; 乔海军; 张卫兵


    Caseins,the main components of milk protein, represent about 80% of the total protein in the milk.Owing to the importance of casein and casein micelles for the functional behavior of dairy products, and widely application of caseins, the study of casein is always drawing more attention.Especially, the exact structure of casein micelles is still under debate.Many scholars have proposed various theoretic models for casein micelle structure. This paper reviewed kinds means of casein micelles structure,dissociation and aggregation in order to provide a reference for studying casein in the future.%酪蛋白是乳中蛋白质的主要成分,约占其80%。由于酪蛋白胶束对乳制品的功能特性起重要作用,因此其研究一直备受关注,但酪蛋白胶束的内部结构至今没有确切的定义,而是许多学者提出了各种理论模型。文章综述了酪蛋白胶束结构、解离与聚集的多种研究方法,为以后学者研究酪蛋白提供借鉴。

  11. Characterization of nanostructured zirconia prepared by hydrolysis and reverse micelle synthesis by small-angle neutron and X-ray scattering

    Thiyagarajan, P.; Li, X.; Littrell, K.; Seifert, S.; Csencsits, R.; Loong, C.


    Low temperature techniques such as hydrolysis and reverse micelle syntheses provide the opportunity to determine the relationship between the structural properties and preparation conditions of zirconia powders as well as to tailor their physicochemical properties. The authors have performed small-angle neutron and synchrotron X-ray scattering (SANS and SAXS) experiments to study the nucleation and organization of zirconia nanoparticles via different preparation routes. First, the formation of reverse micelles in individual and mixed solutions of (ZrOCl{sub 2}+D{sub 2}O)/AOT/C{sub 6}D{sub 5}CD{sub 3}, and (NH{sub 4}OH+H{sub 2}O)/AOT/C{sub 6}D{sub 5}CD{sub 3} systems at water/AOT molar ratio of 20 was characterized. Second, the aggregation of zirconia gels obtained from the reaction of the reverse micelle solutions after heat treatments was studied. Third, the nanostructure of zirconia powders prepared by the reverse micelle method is compared with the corresponding powders prepared by hydrolysis after different heat treatments.

  12. Aggregation behavior and electrical properties of amphiphilic pyrrole-tailed ionic liquids in water, from the viewpoint of dielectric relaxation spectroscopy.

    Fan, Xiaoqing; Zhao, Kongshuang


    The self-aggregation behavior of amphiphilic pyrrole-tailed imidazolium ionic liquids (Py(CH₂)₁₂mim⁺Br⁻: Py = pyrrole, mim = methylimidazolium) in water is investigated by dielectric spectroscopy from 40 Hz to 110 MHz. Dielectric determination shows that the critical micelle concentration (CMC) is 8.5 mM, which is lower than that for traditional ionic surfactants. The thermodynamic parameter of the micellization, the Gibbs free energy ΔG, was calculated for Py(CH₂)₁₂mim⁺Br⁻ and compared to those of the corresponding C(n)mim⁺Br⁻ (n = 12, 14). It was found that the main driven forces of the Py(CH₂)₁₂mim⁺Br⁻ aggregation were hydrophobic interaction and π-π interactions among the adjacent Py groups. Further, the structure of aggregation was speculated theoretically that Py groups partially insert into the alkyl chains and the staggered arrangement in micelles is formed. When the concentration of Py(CH₂)₁₂mim⁺Br⁻ is higher than CMC, two remarkable relaxations which originated from diffusion of counterions and interfacial polarization between the micelles and solution, were observed at about 1.3 MHz and 55 MHz. The relaxation parameters representing the real properties of the whole system were obtained by fitting the experimental data with Cole-Cole equation. A dielectric model characterizing the structure and electrical properties of spherical micelles was proposed by which the conductivity, permittivity and the volume fraction of micelles as well as electrical properties of solution were calculated from the relaxation parameters. An intriguingly high permittivity of about 150 for the micelle was found to be a direct consequence of the strong orientational order of water molecules inside the core of micelle, and essentially is attributed to the special structure of the micelle. Furthermore, the calculation of the interfacial electrokinetic parameters of the micelles, i.e., the surface conductivity, surface charge density

  13. Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

    Giuseppina Raffaini


    Full Text Available Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD, which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties.

  14. Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations

    Mazzaglia, Antonino; Ganazzoli, Fabio


    Summary Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a “bottom up” approach that can provide important information about the initial aggregates of few molecules. The focus is on the interaction pattern of amphiphilic cyclodextrin (aCD), which may interact by mutual inclusion of the substituent groups in the hydrophobic cavity of neighbouring molecules or by dispersion interactions at their lateral surface. We suggest that these aggregates can also form the nucleation stage of larger systems as well as the building blocks of micelles, vesicle, membranes, or generally nanoparticles thus opening new perspectives in the design of aggregates correlating their structures with the pharmaceutical properties. PMID:26734094

  15. Micelles and reverse micelles in the nickel bis(2-ethylhexyl) sulfosuccinate/water/isooctane microemulsion.

    Garza, Cristina; Carbajal-Tinoco, Mauricio D; Castillo, Rolando


    The ternary system Ni(2+)(AOT)(2) (nickel 2-bis[2-ethylhexyl] sulfosuccinate)/water/isooctane presents w/o and o/w microemulsions with a Winsor progression (2Phi-3Phi-2Phi), without the addition of salt; the "fish diagram" was obtained for alpha=0.5 and gamma=0.02-0.22. Using static and dynamic light scattering the micellar size, the ratio of water to surfactant, and the density of micelles for this system were estimated. In addition, the mean interfacial curvature as a function of temperature was obtained.

  16. Surface induced ordering of micelles at the solid-liquid interface

    Gerstenberg, M.C.; Pedersen, J.S.; Smith, G.S.


    The surface induced ordering of triblock copolymer micelles in aqueous solution was measured with neutron reflectivity far above the critical micelle concentration. The scattering length density profiles showed a clear indication of ordered layers of micelles perpendicular to a quartz surface....... The structure and interactions of the micelles were modeled in detail. The convolution of the center distribution of the micelles, obtained from Monte Carlo simulations of hard spheres at a hard wall, and the projected density of the micelle showed excellent agreement with the experimental profiles. [S1063-651X...

  17. Formation and stability of micelles and vesicles

    Engberts, Jan B.F.N.; Kevelam, Jan


    Recent studies on the self-assembly of novel catanionic, bolaform and gemini surfactants provide evidence that the Israelachvili packing parameter approach can often be successfully used to predict the morphology of surfactant aggregates on the basis of the geometrical properties of the surfactant m

  18. Distinguishing aggregate formation and aggregate clearance using cell based assays

    E. Eenjes, E.; J.M. Dragich; H. Kampinga (Harm); A. Yamamoto, A.


    textabstractThe accumulation of ubiquitinated proteinaceous inclusions represents a complex process, reflecting the disequilibrium between aggregate formation and aggregate clearance. Although decreasing aggregate formation or augmenting aggregate clearance will ultimately lead to diminished aggrega

  19. Milk protein suspensions enriched with three essential minerals: Physicochemical characterization and aggregation induced by a novel enzymatic pool.

    Lombardi, Julia; Spelzini, Darío; Corrêa, Ana Paula Folmer; Brandelli, Adriano; Risso, Patricia; Boeris, Valeria


    Structural changes of casein micelles and their aggregation induced by a novel enzymatic pool isolated from Bacillus spp. in the presence of calcium, magnesium or zinc were investigated. The effect of cations on milk protein structure was studied using fluorescence and dynamic light scattering. In the presence of cations, milk protein structure rearrangements and larger casein micelle size were observed. The interaction of milk proteins with zinc appears to be of a different nature than that with calcium or magnesium. Under the experimental conditions assayed, the affinity of each cation for some groups present in milk proteins seems to play an important role, besides electrostatic interaction. On the other hand, the lowest aggregation times were achieved at the highest calcium and zinc concentrations (15 mM and 0.25 mM, respectively). The study found that the faster the aggregation of casein micelles, the less compact the gel matrix obtained. Cation concentrations affected milk protein aggregation kinetics and the structure of the aggregates formed.

  20. Polymeric micelles based on poly(ethylene oxide) and α-carbon substituted poly(ɛ-caprolactone): An in vitro study on the effect of core forming block on polymeric micellar stability, biocompatibility, and immunogenicity.

    Garg, Shyam M; Vakili, Mohammad Reza; Lavasanifar, Afsaneh


    A series of block copolymers based on methoxy poly(ethylene oxide)-block-poly(ɛ-caprolactone) (PEO-b-PCL), PEO-b-PCL bearing side groups of benzyl carboxylate (PEO-b-PBCL), or free carboxyl (PEO-b-PCCL) on the PCL backbone with increasing degrees of polymerization of the PCL backbone were synthesized. Prepared block copolymers assembled to polymeric micelles by co-solvent evaporation. The physical stability of prepared micelles was assessed by measuring their tendency toward aggregation over time using dynamic light scattering (DLS). The resistance of micelles against dissociation in the presence of a micelle destabilizing agent, i.e., sodium dodecyl sulfate (SDS), was also investigated using DLS. The rate of micellar core degradation was determined using (1)H NMR for polymer molecular weight measurement upon incubation of micelles in PBS (pH=7.4) at 37°C followed by dialysis of the remaining polymer at different time intervals. The effect of pendent group chemistry in the micellar core on the adsorption of serum proteins to micellar structure was then evaluated using Bradford Protein assay kit. Finally, the effect of micellar core structure on the induction of bone marrow derived dendritic cell (BMDC) maturation and secretion of IL-12 was studied as a measure of micellar immunogenicity. The results showed micelle structures from polymers with higher degree of polymerization in the hydrophobic block and/or those with more hydrophobic substituents on the core-forming block, to be more stable. This was reflected by a decreased tendency for micellar aggregation, reduced dissociation of micelles in the presence of SDS, and diminished core degradation. All micelles were shown to have insignificant adsorption of serum protein suggesting that the hydrophilic PEO shell provided sufficient protection of the core. However, the protein adsorption increased with increase in the hydrophobicity and molecular weight of the core-forming block. Irrespective of the micellar core

  1. Ageing and hypoxia cause protein aggregation in mitochondria.

    Kaufman, Daniel M; Wu, Xia; Scott, Barbara A; Itani, Omar A; Van Gilst, Marc R; Bruce, James E; Michael Crowder, C


    Aggregation of cytosolic proteins is a pathological finding in disease states, including ageing and neurodegenerative diseases. We have previously reported that hypoxia induces protein misfolding in Caenorhabditis elegans mitochondria, and electron micrographs suggested protein aggregates. Here, we seek to determine whether mitochondrial proteins actually aggregate after hypoxia and other cellular stresses. To enrich for mitochondrial proteins that might aggregate, we performed a proteomics analysis on purified C. elegans mitochondria to identify relatively insoluble proteins under normal conditions (110 proteins identified) or after sublethal hypoxia (65 proteins). A GFP-tagged mitochondrial protein (UCR-11 - a complex III electron transport chain protein) in the normally insoluble set was found to form widespread aggregates in mitochondria after hypoxia. Five other GFP-tagged mitochondrial proteins in the normally insoluble set similarly form hypoxia-induced aggregates. Two GFP-tagged mitochondrial proteins from the soluble set as well as a mitochondrial-targeted GFP did not form aggregates. Ageing also resulted in aggregates. The number of hypoxia-induced aggregates was regulated by the mitochondrial unfolded protein response (UPRmt) master transcriptional regulator ATFS-1, which has been shown to be hypoxia protective. An atfs-1(loss-of-function) mutant and RNAi construct reduced the number of aggregates while an atfs-1(gain-of-function) mutant increased aggregates. Our work demonstrates that mitochondrial protein aggregation occurs with hypoxic injury and ageing in C. elegans. The UPRmt regulates aggregation and may protect from hypoxia by promoting aggregation of misfolded proteins.

  2. The role of casein micelles and their aggregates in foam stabilization

    Chen, Min


    Many foam products derived from milk or specific dairy ingredients suffer from drainage, coalescence and/or disproportionation. Previous studies indicated that foam properties of milk are strongly influenced by the composition of the milk as well as by the processing conditions during foam productio

  3. Population balance modeling of antibodies aggregation kinetics.

    Arosio, Paolo; Rima, Simonetta; Lattuada, Marco; Morbidelli, Massimo


    The aggregates morphology and the aggregation kinetics of a model monoclonal antibody under acidic conditions have been investigated. Growth occurs via irreversible cluster-cluster coagulation forming compact, fractal aggregates with fractal dimension of 2.6. We measured the time evolution of the average radius of gyration, , and the average hydrodynamic radius, , by in situ light scattering, and simulated the aggregation kinetics by a modified Smoluchowski's population balance equations. The analysis indicates that aggregation does not occur under diffusive control, and allows quantification of effective intermolecular interactions, expressed in terms of the Fuchs stability ratio (W). In particular, by introducing a dimensionless time weighed on W, the time evolutions of measured under various operating conditions (temperature, pH, type and concentration of salt) collapse on a single master curve. The analysis applies also to data reported in the literature when growth by cluster-cluster coagulation dominates, showing a certain level of generality in the antibodies aggregation behavior. The quantification of the stability ratio gives important physical insights into the process, including the Arrhenius dependence of the aggregation rate constant and the relationship between monomer-monomer and cluster-cluster interactions. Particularly, it is found that the reactivity of non-native monomers is larger than that of non-native aggregates, likely due to the reduction of the number of available hydrophobic patches during aggregation.

  4. Interfacial aggregation of a nonionic surfactant: Effect on the stability of silica suspensions

    Giordano-Palmino, F.; Denoyel, R.; Rouquerol, J. (CNRS, Marseille (France). Centre de thermodynamique et Microcalorimetrie)


    Nonionic surfactants are in widespread use in technological applications such as flotation, detergency, suspension stabilization (paints, ceramic preparation, pharmaceuticals, cosmetics), and enhanced oil recovery. The adsorption of the nonionic surfactant TX 100 in two silica suspensions (Ludox HS40 and Syton W30) has been studied with the aim of relating the structure of the adsorbed layer to the stability of the suspension. First, a thermodynamic study based on the determination of adsorption isotherms and displacement enthalpies as a function of pH and solid/liquid ratio was carried out and lead to the conclusion that such a surfactant forms micelle-like aggregates on the silica surface. Then, a stability study based on visual observation, turbidimetry, and particle size determination (by photon correlation spectroscopy) was performed in order to determine the TX 100 concentration range in which flocculation occurs. Considering that the surface is covered with micelle-like aggregates in the flocculation range and that the [zeta]-potential (determined by microelectrophoresis) has varied only slightly at the onset of flocculation, it is concluded that the flocculation mechanism is a bridging of particles by surface micelles. This bridging of particles by aggregates similar in size and shape could be an explanation of the presence, in such systems, of optimum flocculation at half surface coverage.

  5. Direct observation and characterization of DMPC/DHPC aggregates under conditions relevant for biological solution NMR.

    van Dam, Lorens; Karlsson, Göran; Edwards, Katarina


    We have used cryo-transmission electron microscopy (cryo-TEM) for inspection of aggregates formed by dimyristoylphosphatidylcholine (DMPC) and dihexanoylphosphatidylcholine (DHPC) in aqueous solution at total phospholipid concentrations cL DHPC ratios q < or = 4.0. In combination with ocular inspections, we are able to sketch out this part of phase-diagram at T = 14-80 degrees C. The temperature and the ratio q are the dominating variables for changing sample morphology, while cL to a lesser extent affects the aggregate structure. At q = 0.5, small, possibly disc-shaped, aggregates with a diameter of approximately 6 nm are formed. At higher q-values, distorted discoidal micelles that tend to short cylindrical micelles are observed. The more well-shaped discs have a diameter of around 20 nm. Upon increasing q or the temperature, long slightly flattened cylindrical micelles that eventually branch are formed. A holey lamellar phase finally appears upon further elevation of q or temperature. The implications for biological NMR work are two. First, discs prepared as membrane mimics are frequently much smaller than predicted by current "ideal bicelle" models. Second, the q approximately 3 preparations used for aligning water-soluble biomolecules in magnetic fields consist of perforated lamellar sheets. Furthermore, the discovered sequence of morphological transitions may have important implications for the development of bicelle-based membrane protein crystallization methods.

  6. Characterisation of aggregation of tributylphosphate molecules in organic solvent; Caracterisation de l'auto-organisation du phosphate de tributyle en solvant organique

    Mandin, C.; Martinet, L.; Zemb, Th.; Berthon, L.; Madic, Ch


    This report presents a structural study of the aggregates formed with the organic phases of the extractant tri-n-butyl phosphate, used in the industrial PUREX process (Plutonium and Uranium Extraction; liquid-liquid solvent extraction) for the treatment of high radioactive waste. Combined Small Angle X-ray Scattering and Small Angle Neutron Scattering show that organic TBP solutions (in equilibrium with acid solutions) are organised in oligomeric aggregates. The influence of various parameters such as HNO{sub 3} or TBP concentrations, diluent or acid natures, does not seem to modify the aggregate shape and size, whereas the interactions are modified. Moreover the aggregates disappear under high temperatures, whereas the attractive interactions between them increase at low temperatures. The 'drop weight' method gives the critical micellar concentration values of TBP in case of H{sub 2}O or HNO{sub 3} extractions (H{sub 2}O: 0.48 M; HNO{sub 3} 2M: 0.65 M; at 21 deg C). Furthermore, the measures at different acid concentrations show that the c.m.c. varies with the acidity. The more acid the aqueous phase is, the smaller is the entropy in the system because of the numerous negative charges, i.e. the harder the micellization occurs, so the higher the c.m.c. value is. The sticky sphere model proposed by Baxter, can be used to model successfully small reverse micelles of the organic TBP phases. The aggregation number would be 4{+-}1 (water extraction) and 5{+-}1(HNO{sub 3}2M extraction). These values are also given by vapor pressure measurements. (authors)

  7. Characterisation of aggregation of tributylphosphate molecules in organic solvent; Caracterisation de l'auto-organisation du phosphate de tributyle en solvant organique

    Mandin, C.; Martinet, L.; Zemb, Th.; Berthon, L.; Madic, Ch


    This report presents a structural study of the aggregates formed with the organic phases of the extractant tri-n-butyl phosphate, used in the industrial PUREX process (Plutonium and Uranium Extraction; liquid-liquid solvent extraction) for the treatment of high radioactive waste. Combined Small Angle X-ray Scattering and Small Angle Neutron Scattering show that organic TBP solutions (in equilibrium with acid solutions) are organised in oligomeric aggregates. The influence of various parameters such as HNO{sub 3} or TBP concentrations, diluent or acid natures, does not seem to modify the aggregate shape and size, whereas the interactions are modified. Moreover the aggregates disappear under high temperatures, whereas the attractive interactions between them increase at low temperatures. The 'drop weight' method gives the critical micellar concentration values of TBP in case of H{sub 2}O or HNO{sub 3} extractions (H{sub 2}O: 0.48 M; HNO{sub 3} 2M: 0.65 M; at 21 deg C). Furthermore, the measures at different acid concentrations show that the c.m.c. varies with the acidity. The more acid the aqueous phase is, the smaller is the entropy in the system because of the numerous negative charges, i.e. the harder the micellization occurs, so the higher the c.m.c. value is. The sticky sphere model proposed by Baxter, can be used to model successfully small reverse micelles of the organic TBP phases. The aggregation number would be 4{+-}1 (water extraction) and 5{+-}1(HNO{sub 3}2M extraction). These values are also given by vapor pressure measurements. (authors)

  8. Applications of polymeric micelles with tumor targeted in chemotherapy

    Ding Hui; Wang Xiaojun; Zhang Song; Liu Xinli, E-mail: [Shandong Polytechnic University, Shandong Provincial Key Laboratory of Microbial Engineering (China)


    Polymeric micelles (PMs) have gained more progress as a carrier system with the quick development of biological and nanoparticle techniques. In particular, PMs with smart targeting can deliver anti-cancer drugs directly into tumor cells at a sustained rate. PMs with core-shell structure (with diameters of 10 {approx} 100 nm) have been prepared by a variety of biodegradable and biocompatible polymers via a self-assembly process. The preparation of polymeric micelles with stimuli-responsive block copolymers or modification of target molecules on polymeric micelles' surface are able to significantly improve the efficiency of drug delivery. Polymeric micelles, which have been considered as a novel promising drug carrier for cancer therapeutics, are rapidly evolving and being introduced in an attempt to overcome several limitations of traditional chemotherapeutics, including water solubility, tumor-specific accumulation, anti-tumor efficacy, and non-specific toxicity. This review describes the preparation of polymeric micelles and the targeted modification which greatly enhance the effects of chemotherapeutic agents.

  9. A novel temperature-responsive micelle for enhancing combination therapy

    Peng CL


    Full Text Available Cheng-Liang Peng,1,* Yuan-I Chen,2,3,* Hung-Jen Liu,2 Pei-Chi Lee,2 Tsai-Yueh Luo,1 Ming-Jium Shieh2,3 1Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, 2Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, 3Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: A novel thermosensitive polymer p(N-isopropylacrylamide-co-poly[ethylene glycol] methyl ether acrylate-block-poly(epsilon-caprolactone, p(NIPAAM-co-PEGMEA-b-PCL, was synthesized and developed as nanomicelles. The hydrophobic heat shock protein 90 inhibitor 17-allylamino-17-demethoxygeldanamycin and the photosensitizer cyanine dye infrared-780 were loaded into the core of the micelles to achieve both chemotherapy and photothermal therapy simultaneously at the tumor site. The release of the drug could be controlled by varying the temperature due to the thermosensitive nature of the micelles. The micelles were less than 200 nm in size, and the drug encapsulation efficiency was >50%. The critical micelle concentrations were small enough to allow micelle stability upon dilution. Data from cell viability and animal experiments indicate that this combination treatment using photothermal therapy with chemotherapy had synergistic effects while decreasing side effects. Keywords: thermosensitive, photothermal therapy, chemotherapy, nanocarrier, control release, synergistic effect

  10. Determination of the critical micelle concentration in simulations of surfactant systems

    Santos, Andrew P.; Panagiotopoulos, Athanassios Z., E-mail: [Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersey 08544 (United States)


    Alternative methods for determining the critical micelle concentration (cmc) are investigated using canonical and grand canonical Monte Carlo simulations of a lattice surfactant model. A common measure of the cmc is the “free” (unassociated) surfactant concentration in the presence of micellar aggregates. Many prior simulations of micellizing systems have observed a decrease in the free surfactant concentration with overall surfactant loading for both ionic and nonionic surfactants, contrary to theoretical expectations from mass-action models of aggregation. In the present study, we investigate a simple lattice nonionic surfactant model in implicit solvent, for which highly reproducible simulations are possible in both the canonical (NVT) and grand canonical (μVT) ensembles. We confirm the previously observed decrease of free surfactant concentration at higher overall loadings and propose an algorithm for the precise calculation of the excluded volume and effective concentration of unassociated surfactant molecules in the accessible volume of the solution. We find that the cmc can be obtained by correcting the free surfactant concentration for volume exclusion effects resulting from the presence of micellar aggregates. We also develop an improved method for determination of the cmc based on the maximum in curvature for the osmotic pressure curve determined from μVT simulations. Excellent agreement in cmc and other micellar properties between NVT and μVT simulations of different system sizes is observed. The methodological developments in this work are broadly applicable to simulations of aggregating systems using any type of surfactant model (atomistic/coarse grained) or solvent description (explicit/implicit)

  11. Membrane-micelle model for humus in soils and sediments and its relation to humification

    Wershaw, Robert L.


    Humification, the process whereby biomass consisting of dead plant and animal remains is converted into soil organic matter (humus), is one of the basic processes of the carbon cycle. The organic compounds that make up plant and animal tissue are thermodynamically unstable in the oxidizing atmosphere at the surface of the Earth. After the organisms in which they are incorporated die, the compounds are converted back to carbon dioxide and water by degradation reactions catalyzed by enzymes secreted by micro-organisms. However, not all the organic compounds in the dead biomass are immediately converted; some of the material is only partially oxidized. The residue left after partial oxidative degradation of the dead biomass is the source of the organic compounds that accumulate in soils and sediments as humus. Previously, humification was thought to involve a conversion of degradation products by a series of polymerization reactions into new types of polymeric species that are different from the precursor molecular species in the original biomass. However, it is proposed here that the depolymerization and oxidation reactions that take place during the enzymatic degradation of biopolymers produce amphiphiles--molecules that have a polar (hydrophilic) part and a nonpolar (hydrophobic) part. These amphiphiles that result from the partial oxidative degradation of dead biomass assemble spontaneously into ordered aggregates in which the hydrophobic parts of the molecules form the interiors and the hydrophilic parts of the molecules make up the exterior surfaces of the aggregates. These ordered aggregates constitute the humus in soils and sediments. Humus ordered aggregates most likely exist as bilayer membranes coating mineral grains and as micelles in solution.

  12. DNA packaging induced by micellar aggregates: a novel in vitro DNA condensation system.

    Ghirlando, R; Wachtel, E J; Arad, T; Minsky, A


    Evidence for a conceptually novel DNA packaging process is presented. X-ray scattering, electron microscopy, and circular dichroism measurements indicate that in the presence of positively charged micellar aggregates and flexible anionic polymers, such as negatively charged polypeptides or single-stranded RNA species, a complex is formed in which DNA molecules are partially embedded within a micellar scaffold and partially condensed into highly packed chiral structures. Based on studies of micelle-DNA and micelle-flexible anionic polymer systems, as well as on the known effects of a high charge density upon the micellar organization, a DNA packaging model is proposed. According to this model, the DNA induces the elongation of the micelles into rodlike aggregates, forming a closely packed matrix in which the DNA molecules are immobilized. In contrast, the flexible anionic polymers stabilize clusters of spherical micelles which are proposed to effect a capping of the rodlike micelles, thus arresting their elongation and creating surfactant-free segments of the DNA that are able to converge and collapse. Thus, unlike other in vitro DNA packaging systems, in which condensation follows encounters between charge-neutralized DNA molecules, a prepackaging phase where the DNA is immobilized within a matrix is proposed in this case. Cellular and nuclear membranes have been implicated in DNA packaging processes in vivo, and negatively charged polyelectrolytes were shown to be involved in the processes. These observations, combined with the basic tenets of the DNA condensation system described here, allow for the progression to the study of more elaborate model systems and thus might lead to insights into the nature and roles of the intricate in vivo DNA-membrane complexes.

  13. Biomimetic oral mucin from polymer micelle networks

    Authimoolam, Sundar Prasanth

    Mucin networks are formed by the complexation of bottlebrush-like mucin glycoprotein with other small molecule glycoproteins. These glycoproteins create nanoscale strands that then arrange into a nanoporous mesh. These networks play an important role in ensuring surface hydration, lubricity and barrier protection. In order to understand the functional behavior in mucin networks, it is important to decouple their chemical and physical effects responsible for generating the fundamental property-function relationship. To achieve this goal, we propose to develop a synthetic biomimetic mucin using a layer-by-layer (LBL) deposition approach. In this work, a hierarchical 3-dimensional structures resembling natural mucin networks was generated using affinity-based interactions on synthetic and biological surfaces. Unlike conventional polyelectrolyte-based LBL methods, pre-assembled biotin-functionalized filamentous (worm-like) micelles was utilized as the network building block, which from complementary additions of streptavidin generated synthetic networks of desired thickness. The biomimetic nature in those synthetic networks are studied by evaluating its structural and bio-functional properties. Structurally, synthetic networks formed a nanoporous mesh. The networks demonstrated excellent surface hydration property and were able capable of microbial capture. Those functional properties are akin to that of natural mucin networks. Further, the role of synthetic mucin as a drug delivery vehicle, capable of providing localized and tunable release was demonstrated. By incorporating antibacterial curcumin drug loading within synthetic networks, bacterial growth inhibition was also demonstrated. Thus, such bioactive interfaces can serve as a model for independently characterizing mucin network properties and through its role as a drug carrier vehicle it presents exciting future opportunities for localized drug delivery, in regenerative applications and as bio

  14. Thermodynamics and Structural Evolution during a Reversible Vesicle-Micelle Transition of a Vitamin-Derived Bolaamphiphile Induced by Sodium Cholate.

    Tian, Jun-Nan; Ge, Bing-Qiang; Shen, Yun-Feng; He, Yu-Xuan; Chen, Zhong-Xiu


    Interaction of endogenous sodium cholate (SC) with dietary amphiphiles would induce structural evolution of the self-assembled aggregates, which inevitably affects the hydrolysis of fat in the gut. Current work mainly focused on the interaction of bile salts with classical double-layered phospholipid vesicles. In this paper, the thermodynamics and structural evolution during the interaction of SC with novel unilamellar vesicles formed from vitamin-derived zwitterionic bolaamphiphile (DDO) were characterized. It was revealed that an increased temperature and the presence of NaCl resulted in narrowed micelle-vesicle coexistence and enlarged the vesicle region. The coexistence of micelles and vesicles mainly came from the interaction of monomeric SC with DDO vesicles, whereas micellar SC contributed to the total solubilization of DDO vesicles. This research may enrich the thermodynamic mechanism behind the structure transition of the microaggregates formed by amphiphiles in the gut. It will also contribute to the design of food formulation and drug delivery system.

  15. Dexamethasone-loaded poly(D, L-lactic acid) microspheres/poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) micelles composite for skin augmentation.

    Fan, Min; Liao, Jinfeng; Guo, Gang; Ding, Qiuxia; Yang, Yi; Luo, Feng; Qian, Zhiyong


    Soft tissue augmentation using various injectable fillers has gained popularity as more patients seek esthetic improvement through minimally invasive procedures requiring little or no recovery time. The currently available injectable skin fillers can be divided into three categories. With careful assessment, stimulatory fillers are the most ideal fillers. In this study, dexamethasone-loaded poly(D, L-lactic acid) (PLA) microspheres of approximately 90 micro m suspended in poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles were prepared as stimulatory filler for skin augmentation. The biodegradable PECE copolymer can form nano-sized micelles in water, which instantly turns into a non-flowing gel at body temperature due to micellar aggregation. The PECE micelles (making up 90% of composite) served as vehicle for subcutaneous injection were metabolized within 44 days. At the same time, the dexamethasone-loaded PLA microspheres (10% of composite) merely served as stimulus for connective tissue formation. Dexamethasone-loaded PLA microspheres/PECE micelles composite presented great hemocompatibility in vitro. It was demonstrated in the in vive study that the composite was biodegradable, biocompatible, nontoxic and nonmigratory. Histopathological studies indicated that the composite could stimulate collagen regeneration. Furthermore, granuloma, the main complication of the stimulatory fillers, did not appear when the composite was injected into the back of SD rats, because of the dexamethasone controlled release from the composite. All results suggested that dexamethasone-loaded PLA microspheres/PECE micelles composite may be an efficient and promising biomaterial for skin augmentation.

  16. Artificial Self-Sufficient P450 in Reversed Micelles

    Teruyuki Nagamune


    Full Text Available Cytochrome P450s are heme-containing monooxygenases that require electron transfer proteins for their catalytic activities. They prefer hydrophobic compounds as substrates and it is, therefore, desirable to perform their reactions in non-aqueous media. Reversed micelles can stably encapsulate proteins in nano-scaled water pools in organic solvents. However, in the reversed micellar system, when multiple proteins are involved in a reaction they can be separated into different micelles and it is then difficult to transfer electrons between proteins. We show here that an artificial self-sufficient cytochrome P450, which is an enzymatically crosslinked fusion protein composed of P450 and electron transfer proteins, showed micelle-size dependent catalytic activity in a reversed micellar system. Furthermore, the presence of thermostable alcohol dehydrogenase promoted the P450-catalyzed reaction due to cofactor regeneration.

  17. Multicompartment Micelles From π-Shaped ABC Block Copolymers

    XIA Jun; ZHONG Chong-Li


    Dissipative particle dynamics simulations were performed on the morphology and structure of multicompartment micelles formed from n-shaped ABC block copolymers in water. The influences of chain architectures were studied in a systematic way, and a rich variety of morphologies were observed, such as spherical, wormlike,X-shaped, Y-shaped, ribbon-like, layered rod-like, layered disk-like, as well as network morphologies. The simulations show that the distance between the two grafts plays an important role in control of the morphology. Since π-shaped ABC block copolymers can be reduced to linear ABC and star ABC block copolymers, they are good model copolymers for studying the self-assembly of complex block copolymers into micelles. The knowledge obtained in this work as well as the new morphologies identified provide useful information for future rational design and synthesis of novel multicompartment micelles.

  18. Enzymatically triggered multifunctional delivery system based on hyaluronic acid micelles

    Deng, Lin


    Tumor targetability and stimuli responsivity of drug delivery systems (DDS) are key factors in cancer therapy. Implementation of multifunctional DDS can afford targetability and responsivity at the same time. Herein, cholesterol molecules (Ch) were coupled to hyaluronic acid (HA) backbones to afford amphiphilic conjugates that can self-assemble into stable micelles. Doxorubicin (DOX), an anticancer drug, and superparamagnetic iron oxide (SPIO) nanoparticles (NPs), magnetic resonance imaging (MRI) contrast agents, were encapsulated by Ch-HA micelles and were selectively released in the presence of hyaluronidase (Hyals) enzyme. Cytotoxicity and cell uptake studies were done using three cancer cell lines (HeLa, HepG2 and MCF7) and one normal cell line (WI38). Higher Ch-HA micelles uptake was seen in cancer cells versus normal cells. Consequently, DOX release was elevated in cancer cells causing higher cytotoxicity and enhanced cell death. © 2012 The Royal Society of Chemistry.

  19. Ionic quenching of naphthalene fluorescence in sodium dodecyl sulfate micelles.

    Silva, Alessandra F; Fiedler, Haidi D; Nome, Faruk


    Micellar effects on luminescense of organic compounds or probes are well established, and here we show that quenching is highly favored in aqueous sodium dodecyl sulfate (SDS) micelles, which concentrate a naphthalene probe and cations of lanthanides, transition metals, and noble metals. Interactions have been studied by steady state and time-resolved fluorescence in examining the fluorescence suppression of naphthalene by metal ions in anionic SDS micelles. The quenching is collisional and correlated with the unit charge and the reduction potential of the metal ion. The rate constants, calculated in terms of local metal ion concentrations, are close to the diffusion control limit in the interior of SDS micelles, where the microscopic viscosity decreases the transfer rate, following the Stokes-Einstein relation.

  20. Anomalous diffusion and stress relaxation in surfactant micelles

    Dhakal, Subas; Sureshkumar, Radhakrishna


    We investigate the mechanisms of anomalous diffusion in cationic surfactant micelles using molecular dynamics simulations in the presence of explicit salt and solvent-mediated interactions. Simulations show that when the counterion density increases, saddle-shaped branched interfaces manifest. In experiments, branched structures exhibit lower viscosity as compared to linear and wormlike micelles. This has long been attributed to stress relaxation arising from the sliding motion of branches along the main chain. Our simulations reveal a mechanism of branch motion resulting from an enhanced counterion condensation at the branched interfaces and provide quantitative evidence of stress relaxation facilitated by branched sliding. Furthermore, depending on the surfactant and salt concentrations, which in turn determine the microstructure, we observe normal, subdiffusive, and superdiffusive motions of surfactants. Specifically, superdiffusive behavior is associated with branch sliding, breakage and recombination of micelle fragments, as well as constraint release in entangled systems.


    Chun-yan Long; Ming-ming Sheng; Bin He; Yao Wu; Gang Wang; Zhong-wei Gu


    An anti-tumor drug doxombicin was encapsulated in micelles of poly(ethylene glycol)-b-poly(2,2-dihydroxyl-methyl propylene carbonate) (PEG-b-PDHPC) diblock copolymers.The morphology of both blank micelles and drug loaded micelles was characterized by TEM.The in vitro drug release profiles of micelles were investigated.The cytotoxicity of the micelles was evaluated by incubating with Hela tumor cells and 3T3 fibroblasts.The drug loaded micelles were co-cultured with HepG2 cells to evaluate the in vitro anti-tumor efficacies.The results showed that the mean sizes of both micelles with different copolymer compositions increased after being loaded with drugs.The drug release rate of PEG45-b-PDHPC34 micelles was faster than that of rnPEG114-b-PDHPC26 micelles.Both of the two block copolymers were non-toxic.The confocal laser scanning microscopy and flow cytometry results showed that both the drug loaded micelles could be internalized efficiently in HepG2 cells.The PEG45-b-PDHPC34 micelles exhibited higher anti-tumor activity comparing to mPEG114-b-PDHPC26 micelles.

  2. Controlled mixing of lanthanide(III) ions in coacervate core micelles.

    Wang, Junyou; Velders, Aldrik H; Gianolio, Eliana; Aime, Silvio; Vergeldt, Frank J; Van As, Henk; Yan, Yun; Drechsler, Markus; de Keizer, Arie; Cohen Stuart, Martien A; van der Gucht, Jasper


    This article presents a facile strategy to combine Eu(3+) and Gd(3+) ions into coacervate core micelles in a controlled way with a statistical distribution of the ions. Consequently, the formed micelles show a high tunability between luminescence and relaxivity. These highly stable micelles present great potential for new materials, e.g. as bimodal imaging probes.

  3. Shell and core cross-linked poly(L-lysine)/poly(acrylic acid) complex micelles.

    Hsieh, Yi-Hsuan; Hsiao, Yung-Tse; Jan, Jeng-Shiung


    We report the versatility of polyion complex (PIC) micelles for the preparation of shell and core cross-linked (SCL and CCL) micelles with their surface properties determined by the constituent polymer composition and cross-linking agent. The negatively and positively charged PIC micelles with their molecular structure and properties depending on the mixing weight percentage and polymer molecular weight were first prepared by mixing the negatively and positively charged polyions, poly(acrylic acid) (PAA) and poly(L-lysine) (PLL). The feasibility of preparing SCL micelles was demonstrated by cross-linking the shell of the negatively and positively charged micelles using cystamine and genipin, respectively. The core of the micelles can be cross-linked by silica deposition to stabilize the assemblies. The shell and/or core cross-linked micelles exhibited excellent colloid stability upon changing solution pH. The drug release from the drug-loaded SCL micelles revealed that the controllable permeability of the SCL micelles can be achieved by tuning the cross-linking degree and the SCL micelles exhibited noticeable pH-responsive behavior with accelerated release under acidic conditions. With the versatility of cross-linking strategies, it is possible to prepare a variety of SCL and CCL micelles from PIC micelles.

  4. Curcumin and Osteosarcoma: Can Invertible Polymeric Micelles Help?

    Avudaiappan Maran


    Full Text Available Systematic review of experimental and clinical data on the use of curcumin in the treatment of osteosarcoma is presented. The current status of curcumin’s therapeutic potential against bone cancer is analyzed in regard to using polymeric micelles (including recently developed invertible, responsive, micelles as a platform for curcumin delivery to treat osteosarcoma. The potential of micellar assemblies from responsive macromolecules in a controlled delivery of curcumin to osteosarcoma cells, and the release using a new inversion mechanism is revealed.

  5. Folding of DsbB in mixed micelles

    Otzen, Daniel


    is sensitive to changes in lipid and detergent composition. As an attempt to overcome this problem, I present a kinetic analysis of the folding of a membrane protein, disulfide bond reducing protein B (DsbB), in a mixed micelle system consisting of varying molar ratios of sodium dodecyl sulfate (SDS...... data are always open to alternative interpretations, time-resolved studies in mixed micelles provide a useful approach to measure membrane protein stability over a wide range of concentrations of SDS and DM, as well as a framework for the future characterization of the DsbB folding mechanism....

  6. Solubilization of benzene and cyclohexane by sodium deoxycholate micelles

    Christian, S.D.; Smith, L.S.; Bushong, D.S.; Tucker, E.E.


    Vapor pressure-solubility data were obtained for the aqueous systems benzene-sodium deoxycholate and cyclohexane- sodium deoxycholate at 25/sup 0/C. The results are consistent with a mass action model similar to the BET equation. Equilibrium constants are inferred to characterize interactions of hydrocarbons with solubilization sites assumed to consist of units of four deoxycholate anions. Although addition of sodium chloride increases the middle aggregation number, solubilization results are affected very little by variation in salt concentration. When pure liquid hydrocarbon standard states are employed, solubilization results for benzene and cyclohexane (at varying salt concentrations) are quite similar. 26 references.

  7. Marine particle aggregate breakup in turbulent flows

    Rau, Matthew; Ackleson, Steven; Smith, Geoffrey


    The dynamics of marine particle aggregate formation and breakup due to turbulence is studied experimentally. Aggregates of clay particles, initially in a quiescent aggregation tank, are subjected to fully developed turbulent pipe flow at Reynolds numbers of up to 25,000. This flow arrangement simulates the exposure of marine aggregates in coastal waters to a sudden turbulent event. Particle size distributions are measured by in-situ sampling of the small-angle forward volume scattering function and the volume concentration of the suspended particulate matter is quantified through light attenuation measurements. Results are compared to measurements conducted under laminar and turbulent flow conditions. At low shear rates, larger sized particles indicate that aggregation initially governs the particle dynamics. Breakup is observed when large aggregates are exposed to the highest levels of shear in the experiment. Models describing the aggregation and breakup rates of marine particles due to turbulence are evaluated with the population balance equation and results from the simulation and experiment are compared. Additional model development will more accurately describe aggregation dynamics for remote sensing applications in turbulent marine environments.

  8. Binding of chloroquine to ionic micelles: Effect of pH and micellar surface charge

    Souza Santos, Marcela de, E-mail: [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, Ribeirão Preto, São Paulo 14040-903 (Brazil); Perpétua Freire de Morais Del Lama, Maria, E-mail: [Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n, Ribeirão Preto, São Paulo 14040-903 (Brazil); Instituto Nacional de Ciência e Tecnologia de Bioanalítica, Departamento de Química Analítica, Universidade Estadual de Campinas, Cidade Universitária Zeferino Vaz, s/n, Campinas, São Paulo 13083-970 (Brazil); Siuiti Ito, Amando, E-mail: [Departamento de Física, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes, 3900, Ribeirão Preto, São Paulo 14040-901 (Brazil); and others


    The pharmacological action of chloroquine relies on its ability to cross biological membranes in order to accumulate inside lysosomes. The present work aimed at understanding the basis for the interaction between different chloroquine species and ionic micelles of opposite charges, the latter used as a simple membrane model. The sensitivity of absorbance and fluorescence of chloroquine to changes in its local environment was used to probe its interaction with cetyltrimethylammonium micelles presenting bromide (CTAB) and sulfate (CTAS) as counterions, in addition to dodecyl sulfate micelles bearing sodium (SDS) and tetramethylammonium (TMADS) counterions. Counterion exchange was shown to have little effect on drug–micelle interaction. Chloroquine first dissociation constant (pKa{sub 1}) shifted to opposite directions when anionic and cationic micelles were compared. Chloroquine binding constants (K{sub b}) revealed that electrostatic forces mediate charged drug–micelle association, whereas hydrophobic interactions allowed neutral chloroquine to associate with anionic and cationic micelles. Fluorescence quenching studies indicated that monoprotonated chloroquine is inserted deeper into the micelle surface of anionic micelles than its neutral form, the latter being less exposed to the aqueous phase when associated with cationic over anionic assemblies. The findings provide further evidence that chloroquine–micelle interaction is driven by a tight interplay between the drug form and the micellar surface charge, which can have a major effect on the drug biological activity. -- Highlights: • Chloroquine (CQ) pKa{sub 1} increased for SDS micelles and decreased for CTAB micelles. • CQ is solubilized to the surface of both CTAB and SDS micelles. • Monoprotonated CQ is buried deeper into SDS micelles than neutral CQ. • Neutral CQ is less exposed to aqueous phase in CTAB over SDS micelles. • Local pH and micellar surface charge mediate interaction of CQ with

  9. Structure and kinetics of shear aggregation in turbulent flows. I. Early stage of aggregation.

    Bäbler, Matthäus U; Moussa, Amgad S; Soos, Miroslav; Morbidelli, Massimo


    Aggregation of rigid colloidal particles leads to fractal-like structures that are characterized by a fractal dimension d(f) which is a key parameter for describing aggregation processes. This is particularly true in shear aggregation where d(f) strongly influences aggregation kinetics. Direct measurement of d(f) in the early stages of shear aggregation is however difficult, as the aggregates are small and few in number. An alternative method for determining d(f) is to use an aggregation model that when fitted to the time evolution of the cluster mass distribution allows for estimating d(f). Here, we explore three such models, two of which are based on an effective collision sphere and one which directly incorporates the permeable structure of the aggregates, and we apply them for interpreting the initial aggregate growth measured experimentally in a turbulent stirred tank reactor. For the latter, three polystyrene latexes were used that differed only in the size of the primary particles (d(p) = 420, 600, and 810 nm). It was found that all three models describe initial aggregation kinetics reasonably well using, however, substantially different values for d(f). To discriminate among the models, we therefore also studied the regrowth of preformed aggregates where d(f) was experimentally accessible. It was found that only the model that directly incorporates the permeable structure of the aggregates is able to predict correctly this second type of experiments. Applying this model to the initial aggregation kinetics, we conclude that the actual initial fractal dimension is d(f) = 2.07 +/- 0.04 as found from this model.

  10. Photophysics in single light-harvesting complexes II: from micelle to native nanodisks

    Gruber, J. Michael; Scheidelaar, Stefan; van Roon, Henny; Dekker, Jan P.; Killian, J. Antoinette; van Grondelle, Rienk


    Most photosynthetic pigment-protein complexes of algae and higher plants are integral membrane proteins and are thus usually isolated in the presence of detergent to provide a hydrophobic interface and prevent aggregation. It was recently shown that the styrene maleic acid (SMA) copolymer can be used instead to solubilize and isolate protein complexes with their native lipid environment into nanodisk particles. We isolated LHCII complexes in SMA and compared their photophysics with trimeric LHCII complexes in β-DM detergent micelles to understand the effect of the native environment on the function of light-harvesting antennae. The triplet state kinetics and the calculated relative absorption cross section of single complexes indicate the successful isolation of trimeric complexes in SMA nanodisks, confirming the trimeric structure as the likely native configuration. The survival time of complexes before they photobleach is increased in SMA compared to detergent which might be explained by a stabilizing effect of the co-purified lipids in nanodisks. We furthermore find an unquenched fluorescence lifetime of 3.5 ns for LHCII in SMA nanodisks which coincides with detergent isolated complexes and notably differs from 2 ns typically found in native thylakoid structures. A large dynamic range of partially quenched complexes both in detergent micelles and lipid nanodisks is demonstrated by correlating the fluorescence lifetime with the intensity and likely reflects the conformational freedom of these complexes. This further supports the hypothesis that fluorescence intermittency is an intrinsic property of LHCII that may be involved in excess energy dissipation in native light-harvesting.

  11. Static structure factor of polymerlike micelles: Overall dimension, flexibility, and local properties of lecithin reverse micelles in deuterated isooctane

    Jerke, G.; Pedersen, J.S.; Egelhaaf, S.U.


    We report a systematic investigation of the static structure factor S(q,c) of polymerlike reverse micelles formed by soybean lecithin and trace amounts of water in deuterated isooctane using small-angle neutron scattering and static light scattering. The experimental data for different concentrat......We report a systematic investigation of the static structure factor S(q,c) of polymerlike reverse micelles formed by soybean lecithin and trace amounts of water in deuterated isooctane using small-angle neutron scattering and static light scattering. The experimental data for different...

  12. Aggregations in Flatworms.

    Liffen, C. L.; Hunter, M.


    Described is a school project to investigate aggregations in flatworms which may be influenced by light intensity, temperature, and some form of chemical stimulus released by already aggregating flatworms. Such investigations could be adopted to suit many educational levels of science laboratory activities. (DS)

  13. Platelet activation and aggregation

    Jensen, Maria Sander; Larsen, O H; Christiansen, Kirsten


    This study introduces a new laboratory model of whole blood platelet aggregation stimulated by endogenously generated thrombin, and explores this aspect in haemophilia A in which impaired thrombin generation is a major hallmark. The method was established to measure platelet aggregation initiated...

  14. Role of Synthetic and Dimensional Synthetic Organic Chemistry in Block Copolymer Micelle Nanosensor Engineering

    Ek, Pramod Kumar

    micelles. Shell cross-linking on PEG-b-PAEMA-b-PS micelles was performed by amidation reactions between the amino groups of PAEMA blocks using a di-carboxylic acid cross-linker. Also a dendritic cross-linker based click chemistry was used to stabilize the PEG-b-PAEMA-b-PES micelle having click readied PES...... micellisation of these functionalized unimers followed by dendritic click shell cross-linking resulted in a stable cRGDfK targeted mixed micelle pH nanosensor. Thus, the engineerability of triblock core-shell-corona micelle was utilized for the synthesis of ratiometric pH nanosensor having desired p...

  15. Aggregates from mineral wastes

    Baic Ireneusz


    Full Text Available The problem concerning the growing demand for natural aggregates and the need to limit costs, including transportation from remote deposits, cause the increase in growth of interest in aggregates from mineral wastes as well as in technologies of their production and recovery. The paper presents the issue related to the group of aggregates other than natural. A common name is proposed for such material: “alternative aggregates”. The name seems to be fully justified due to adequacy of this term because of this raw materials origin and role, in comparison to the meaning of natural aggregates based on gravel and sand as well as crushed stones. The paper presents characteristics of the market and basic application of aggregates produced from mineral wastes, generated in the mining, power and metallurgical industries as well as material from demolished objects.

  16. Interactions of Pluronic nanocarriers with 2D and 3D cell cultures: Effects of PEO block length and aggregation state.

    Arranja, Alexandra; Denkova, Antonia G; Morawska, Karolina; Waton, Gilles; van Vlierberghe, Sandra; Dubruel, Peter; Schosseler, François; Mendes, Eduardo


    This work reveals how the physicochemical properties of Pluronic block copolymers influence significantly their interactions with cancer cells, whether in monolayer or spheroid cultures, and how different clinical applications can be foreseen. Two-dimensional (2D) and three-dimensional (3D) cell culture models were used to investigate the interactions of Pluronic carriers with different PEO block length and aggregation state (unimers versus cross-linked micelles) in HeLa and U87 cancer cells. Stabilized micelles of Pluronic P94 or F127 were obtained by polymerization of a crosslinking agent in the micelles hydrophobic core. Nanocarriers were functionalized with a fluorescent probe for visualization, and with a chelator for radiolabeling with Indium-111 and gamma-quantification. The 2D cell models revealed that the internalization pathways and ultimate cellular localization of the Pluronic nanocarriers depended largely on both the PEO block size and aggregation state of the copolymers. The smaller P94 unimers with an average radius of 2.1nm and the shortest PEO block mass (1100gmol(-1)) displayed the highest cellular uptake and retention. 3D tumor spheroids were used to assess the penetration capacity and toxicity potential of the nanocarriers. Results showed that cross-linked F127 micelles were more efficiently delivered across the tumor spheroids, and the penetration depth depends mostly on the transcellular transport of the carriers. The Pluronic P94-based carriers with the shortest PEO block length induced spheroid toxicity, which was significantly influenced by the spheroid cellular type.

  17. Biodegradable polymeric micelle-encapsulated doxorubicin suppresses tumor metastasis by killing circulating tumor cells

    Deng, Senyi; Wu, Qinjie; Zhao, Yuwei; Zheng, Xin; Wu, Ni; Pang, Jing; Li, Xuejing; Bi, Cheng; Liu, Xinyu; Yang, Li; Liu, Lei; Su, Weijun; Wei, Yuquan; Gong, Changyang


    Circulating tumor cells (CTCs) play a crucial role in tumor metastasis, but it is rare for any chemotherapy regimen to focus on killing CTCs. Herein, we describe doxorubicin (Dox) micelles that showed anti-metastatic activity by killing CTCs. Dox micelles with a small particle size and high encapsulation efficiency were obtained using a pH-induced self-assembly method. Compared with free Dox, Dox micelles exhibited improved cytotoxicity, apoptosis induction, and cellular uptake. In addition, Dox micelles showed a sustained release behavior in vitro, and in a transgenic zebrafish model, Dox micelles exhibited a longer circulation time and lower extravasation from blood vessels into surrounding tissues. Anti-tumor and anti-metastatic activities of Dox micelles were investigated in transgenic zebrafish and mouse models. In transgenic zebrafish, Dox micelles inhibited tumor growth and prolonged the survival of tumor-bearing zebrafish. Furthermore, Dox micelles suppressed tumor metastasis by killing CTCs. In addition, improved anti-tumor and anti-metastatic activities were also confirmed in mouse tumor models, where immunofluorescent staining of tumors indicated that Dox micelles induced more apoptosis and showed fewer proliferation-positive cells. There were decreased side effects in transgenic zebrafish and mice after administration of Dox micelles. In conclusion, Dox micelles showed stronger anti-tumor and anti-metastatic activities and decreased side effects both in vitro and in vivo, which may have potential applications in cancer therapy.

  18. Polymeric micelles in anticancer therapy : Targeting, imaging and triggered release

    Oerlemans, Chris; Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J. Frank W.; Hennink, Wim E.


    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

  19. Complex coacervate core micelles with a lysozyme-modified corona

    Danial, M.; Klok, H.A.; Norde, W.; Cohen Stuart, M.A.


    This paper describes the preparation, characterization, and enzymatic activity of complex coacervate core micelles (C3Ms) composed of poly(acrylic acid) (PAA) and poly(N-methyl-2-vinyl pyridinium iodide)-b-poly(ethylene oxide) (PQ2VP-PEO) to which the antibacterial enzyme lysozyme is end-attached.

  20. In vivo toxicity of cationic micelles and liposomes

    Knudsen, Kristina Bram; Northeved, Helle; Ek, Pramod Kumar


    This study investigated toxicity of nanocarriers comprised of cationic polymer and lipid components often used in gene and drug delivery, formulated as cationic micelles and liposomes. Rats were injected intravenously with 10, 25 or 100 mg/kg and sacrificed after 24 or 48 h, or 24 h after the last...

  1. Polymeric micelles in anticancer therapy : Targeting, imaging and triggered release

    Oerlemans, Chris; Bult, Wouter; Bos, Mariska; Storm, Gert; Nijsen, J. Frank W.; Hennink, Wim E.


    Micelles are colloidal particles with a size around 5-100 nm which are currently under investigation as carriers for hydrophobic drugs in anticancer therapy. Currently, five micellar formulations for anticancer therapy are under clinical evaluation, of which Genexol-PM has been FDA approved for use

  2. The Critical Micelle Concentration of Asphaltenes as Measured by Calorimetry

    Andersen, Simon Ivar; Christensen, S. D.


    Micellization of asphaltenes in solution has been investigated using a micro calorimetric titration procedure (Andersen, S. I.; Birdi, K. S. J Colloid Interface Sci. 1991, 142, 497). The method uses the analysis of heat of dissociation and dilution of asphaltene micelles when a pure solvent (or s...

  3. Extraction of L-Aspartic Acid with Reverse Micelle System

    Özlem AYDOĞAN


    Full Text Available The aim of this study is to investigate the extraction L-aspartic acid which is a hydrophobic amino acid with reverse micelle system. Production of amino acids by fermentation has been more important in recent years. These amino acids are obtained in dilute aqueous solutions and have to be separated from excess substrate, inorganic salts and by-products. Recently, separation of amino acids from fermentation media by reverse micelle extraction has received a great deal of attention. In this study, reverse micelle phase includes aliquat-336 as a surfactant, 1-decanol as a co-surfactant and isooctane as an apolar solvent. Experiments were performed at 150 rpm stirring rate, at 30 oC, for 30 min extraction time with equal volumes of reverse micelle and aqueous phases. Concentration of L-aspartic acid was analyzed by liquid chromatography (HPLC. The extraction yield increased with increasing pH and aliquat-336 concentration and with decreasing initial amino acid concentration. Maximum ekstraction yield (68 % was obtained at pH of 12, surfactant concentration of 200 mM and an initial amino acid concentration of 5 mM.

  4. Molecular dynamics simulation of a polysorbate 80 micelle in water

    Amani, Amir; York, Peter; de Waard, Hans; Anwar, Jamshed


    The structure and dynamics of a single molecule of the nonionic surfactant polysorbate 80 (POE (20) sorbitan monooleate; Tween 80 (R)) as well as a micelle comprising sixty molecules of polysorbate 80 in water have been investigated by molecular dynamics simulation. In its free state in water the po

  5. Fluorescence dynamics of green fluorescent protein in AOT reversed micelles

    Uskova, M.A.; Borst, J.W.; Hink, M.A.; Hoek, van A.; Schots, A.; Klyachko, N.L.; Visser, A.J.W.G.


    We have used the enhanced green fluorescent protein (EGFP) to investigate the properties of surfactant-entrapped water pools in organic solvents (reversed micelles) with steady-state and time-resolved fluorescence methods. The surfactant used was sodium bis(2-ethylhexyl)sulfosuccinate (AOT) and the

  6. Targeted therapy of colorectal neoplasia with rapamycin in peptide-labeled pegylated octadecyl lithocholate micelles.

    Khondee, Supang; Rabinsky, Emily F; Owens, Scott R; Joshi, Bishnu P; Qiu, Zhen; Duan, Xiyu; Zhao, Lili; Wang, Thomas D


    Many powerful drugs have limited clinical utility because of poor water solubility and high systemic toxicity. Here, we formulated a targeted nanomedicine, rapamycin encapsulated in pegylated octadecyl lithocholate micelles labeled with a new ligand for colorectal neoplasia, LTTHYKL peptide. CPC;Apc mice that spontaneously develop colonic adenomas were treated with free rapamycin, plain rapamycin micelles, and peptide-labeled rapamycin micelles via intraperitoneal injection for 35days. Endoscopy was performed to monitor adenoma regression in vivo. We observed complete adenoma regression at the end of therapy. The mean regression rate for peptide-labeled rapamycin micelles was significantly greater than that for plain rapamycin micelles, Prapamycin micelles compared to that of free drug, and no other toxicities were found on chemistries. Together, this unique targeted micelle represents a potential therapeutic for colorectal neoplasia with comparable therapeutic efficacy to rapamycin free drug and significantly less systemic toxicity.

  7. Periodic behavior of lanthanide coordination within reverse micelles.

    Ellis, Ross J; Meridiano, Yannick; Chiarizia, Renato; Berthon, Laurence; Muller, Julie; Couston, Laurent; Antonio, Mark R


    Trends in lanthanide(III) (Ln(III)) coordination were investigated within nanoconfined solvation environments. Ln(III) ions were incorporated into the cores of reverse micelles (RMs) formed with malonamide amphiphiles in n-heptane by contact with aqueous phases containing nitrate and Ln(III); both insert into pre-organized RM units built up of DMDOHEMA (N,N'-dimethyl-N,N'-dioctylhexylethoxymalonamide) that are either relatively large and hydrated or small and dry, depending on whether the organic phase is acidic or neutral, respectively. Structural aspects of the Ln(III) complex formation and the RM morphology were obtained by use of XAS (X-ray absorption spectroscopy) and SAXS (small-angle X-ray scattering). The Ln(III) coordination environments were determined through use of L(3)-edge XANES (X-ray absorption near edge structure) and EXAFS (extended X-ray absorption fine structure), which provide metrical insights into the chemistry across the period. Hydration numbers for the Eu species were measured using TRLIFS (time-resolved laser-induced fluorescence spectroscopy). The picture that emerges from a system-wide perspective of the Ln-O interatomic distances and number of coordinating oxygen atoms for the extracted complexes of Ln(III) in the first half of the series (i.e., Nd, Eu) is that they are different from those in the second half of the series (i.e., Tb, Yb): the number of coordinating oxygen atoms decrease from 9O for early lanthanides to 8O for the late ones--a trend that is consistent with the effect of the lanthanide contraction. The environment within the RM, altered by either the presence or absence of acid, also had a pronounced influence on the nitrate coordination mode; for example, the larger, more hydrated, acidic RM core favors monodentate coordination, whereas the small, dry, neutral core favors bidentate coordination to Ln(III). These findings show that the coordination chemistry of lanthanides within nanoconfined environments is neither

  8. Reverse micelles as suitable microreactor for increased biohydrogen production

    Pandey, Anjana [Nanotechnology and Molecular Biology Laboratory, Centre of Biotechnology, University of Allahabad, Allahabad 211002 (India); Pandey, Ashutosh [Centre of Energy Studies, MNNIT, Allahabad 211004 (India)


    Reverse micelles have been shown to act as efficient microreactors for enzymic reactions and whole cell entrapment in organic (non-aqueous) media wherein the reactants are protected from denaturation by the surrounding organic solvent. These micelles are thermodynamically stable, micrometer sized water droplets dispersed in an organic phase by a surfactant. It has been observed that when whole cells of photosynthetic bacteria (Rhodopseudomonas sphaeroides or Rhodobacter sphaeroides 2.4.1) are entrapped inside these reverse micelles, the H{sub 2} production enhanced from 25 to 35 folds. That is, 1.71mmol(mgprotein){sup -1}h{sup -1} in case of R. sphaeroides which is 25 fold higher in benzene-sodium lauryl sulfate reverse micelles. Whereas, in case of R. sphaeroides 2.4.1 the H{sub 2} production was increased by 35 fold within AOT-isooctane reverse micelles i.e. 11.5mmol(mgprotein){sup -1}h{sup -1}. The observations indicate that the entrapment of whole cells of microbes within reverse micelles provides a novel and efficient technique to produce hydrogen by the inexhaustible biological route. The two microorganisms R. sphaeroides 2.4.1 (a photosynthetic bacteria) and Citrobacter Y19 (a facultative anaerobic bacteria) together are also entrapped within AOT-isooctane and H{sub 2} production was measured i.e. 69mmol(mgprotein){sup -1}h{sup -1}. The nitrogenase enzyme responsible for hydrogen production by R. sphaeroides/R. sphaeroides 2.4.1 cells is oxygen sensitive, and very well protected within reverse micelles by the use of combined approach of two cells (R. sphaeroides 2.4.1 and Citrobacter Y19). In this case glucose present in the medium of Citrobacter Y19 serves double roles in enhancing the sustained production rate of hydrogen. Firstly, it quenches the free O{sub 2}liberated as a side product of reaction catalyzed by nitrogenase, which is O{sub 2} labile. Secondly, organic acid produced by this reaction is utilized by the Citrobacter Y19 as organic substrate in

  9. Dynamics of proteins aggregation. I. Universal scaling in unbounded media

    Zheng, Size; Javidpour, Leili; Shing, Katherine S.; Sahimi, Muhammad


    It is well understood that in some cases proteins do not fold correctly and, depending on their environment, even properly-folded proteins change their conformation spontaneously, taking on a misfolded state that leads to protein aggregation and formation of large aggregates. An important factor that contributes to the aggregation is the interactions between the misfolded proteins. Depending on the aggregation environment, the aggregates may take on various shapes forming larger structures, such as protein plaques that are often toxic. Their deposition in tissues is a major contributing factor to many neuro-degenerative diseases, such as Alzheimer's, Parkinson's, amyotrophic lateral sclerosis, and prion. This paper represents the first part in a series devoted to molecular simulation of protein aggregation. We use the PRIME, a meso-scale model of proteins, together with extensive discontinuous molecular dynamics simulation to study the aggregation process in an unbounded fluid system, as the first step toward MD simulation of the same phenomenon in crowded cellular environments. Various properties of the aggregates have been computed, including dynamic evolution of aggregate-size distribution, mean aggregate size, number of peptides that contribute to the formation of β sheets, number of various types of hydrogen bonds formed in the system, radius of gyration of the aggregates, and the aggregates' diffusivity. We show that many of such quantities follow dynamic scaling, similar to those for aggregation of colloidal clusters. In particular, at long times the mean aggregate size S(t) grows with time as, S(t) ˜ tz, where z is the dynamic exponent. To our knowledge, this is the first time that the qualitative similarity between aggregation of proteins and colloidal aggregates has been pointed out.

  10. Small-angle neutron scattering studies of sodium butyl benzene sulfonate aggregates in aqueous solution

    O R Pal; V G Gaikar; J V Joshi; P S Goyal; V K Aswal


    The aggregation behaviour of a hydrotrope, sodium -butyl benzene sulfonate (Na-NBBS), in aqueous solutions is investigated by small-angle neutron scattering (SANS). Nearly ellipsoidal aggregates of Na-NBBS at concentrations well above its minimum hydrotrope concentration were detected by SANS. The hydrotrope seems to form self-assemblies with aggregation number of 36–40 with a substantial charge on the aggregate. This aggregation number is weakly affected by the hydrotrope concentration.

  11. Protein aggregate myopathies

    Sharma M


    Full Text Available Protein aggregate myopathies (PAM are an emerging group of muscle diseases characterized by structural abnormalities. Protein aggregate myopathies are marked by the aggregation of intrinsic proteins within muscle fibers and fall into four major groups or conditions: (1 desmin-related myopathies (DRM that include desminopathies, a-B crystallinopathies, selenoproteinopathies caused by mutations in the, a-B crystallin and selenoprotein N1 genes, (2 hereditary inclusion body myopathies, several of which have been linked to different chromosomal gene loci, but with as yet unidentified protein product, (3 actinopathies marked by mutations in the sarcomeric ACTA1 gene, and (4 myosinopathy marked by a mutation in the MYH-7 gene. While PAM forms 1 and 2 are probably based on impaired extralysosomal protein degradation, resulting in the accumulation of numerous and diverse proteins (in familial types in addition to respective mutant proteins, PAM forms 3 and 4 may represent anabolic or developmental defects because of preservation of sarcomeres outside of the actin and myosin aggregates and dearth or absence of other proteins in these actin or myosin aggregates, respectively. The pathogenetic principles governing protein aggregation within muscle fibers and subsequent structural sarcomeres are still largely unknown in both the putative catabolic and anabolic forms of PAM. Presence of inclusions and their protein composition in other congenital myopathies such as reducing bodies, cylindrical spirals, tubular aggregates and others await clarification. The hitherto described PAMs were first identified by immunohistochemistry of proteins and subsequently by molecular analysis of their genes.

  12. Charged Dust Aggregate Interactions

    Matthews, Lorin; Hyde, Truell


    A proper understanding of the behavior of dust particle aggregates immersed in a complex plasma first requires a knowledge of the basic properties of the system. Among the most important of these are the net electrostatic charge and higher multipole moments on the dust aggregate as well as the manner in which the aggregate interacts with the local electrostatic fields. The formation of elongated, fractal-like aggregates levitating in the sheath electric field of a weakly ionized RF generated plasma discharge has recently been observed experimentally. The resulting data has shown that as aggregates approach one another, they can both accelerate and rotate. At equilibrium, aggregates are observed to levitate with regular spacing, rotating about their long axis aligned parallel to the sheath electric field. Since gas drag tends to slow any such rotation, energy must be constantly fed into the system in order to sustain it. A numerical model designed to analyze this motion provides both the electrostatic charge and higher multipole moments of the aggregate while including the forces due to thermophoresis, neutral gas drag, and the ion wakefield. This model will be used to investigate the ambient conditions leading to the observed interactions. This research is funded by NSF Grant 1414523.

  13. Aggregated Computational Toxicology Online Resource

    U.S. Environmental Protection Agency — Aggregated Computational Toxicology Online Resource (AcTOR) is EPA's online aggregator of all the public sources of chemical toxicity data. ACToR aggregates data...

  14. A small-angle neutron scattering study of the structure of graphitized carbon black aggregates in Triton X-100/water solutions

    Garamus, V.M.; Pedersen, J.S.


    The structure of graphitized carbon black (CB) aggregates dispersed in water solutions with a non-ionic surfactant are studied by small-angle neutron scattering using contrast variation by heavy/light water mixing. The addition of CB to Triton X-100/water mixtures shifts the critical micelle...... particles is 8% and is constant with varying CB and surfactant concentration. The volume fraction of the voids does not exceed 1% of the CB; The micelle structure is found to be the same as in surfactant/water solutions. (C) 1998 Elsevier Science B.V....

  15. Mechanical and thermodynamic properties of surfactant aggregates at the solid-liquid interface.

    Rabinovich, Yakov I; Vakarelski, Ivan U; Brown, Scott C; Singh, Pankaj K; Moudgil, Brij M


    Surfactants are widely used to stabilize colloidal systems in a variety of industrial applications through the formation of self-assembled aggregates at the solid-liquid interface. Previous studies have reported that the control of surfactant-mediated slurry stability can be achieved through the manipulation of surfactant chain length and concentration. However, a fundamental understanding of the mechanical and energetic properties of these aggregates, which may aid in the molecular-level design of these systems, is still lacking. In this study, experimentally measured force/distance curves between an atomic force microscope (AFM) tip and self-assembled surfactant aggregates on mica or silica substrates at concentrations higher than the bulk critical micelle concentration (CMC) were used to determine their mechanical and thermodynamic properties. The experimental curves were fitted to a model which describes the interaction between a hard sphere (tip) and a soft substrate (surfactant structures) based on a modified Hertz theory for the case of a thin elastic layer on a rigid substrate. The calculated mechanical properties were found to be in the same order of magnitude as those reported for rubber-like materials (e.g., polydimethylsiloxane (PDMS)). By integrating the force/distance curves, the energy required for breaking the surface aggregates was also calculated. These values are close to those reported for bulk-micelle formation.

  16. Solvation dynamics of DCM in a polypeptide-surfactant aggregate: gelatin-sodium dodecyl sulfate.

    Halder, Arnab; Sen, Pratik; Burman, Anupam Das; Bhattacharyya, Kankan


    Solvation dynamics of 4-(dicyanomethylidene)-2-[p-(dimethylamino)styryl]-6-methyl-4H-pyran (DCM) is studied in a polypeptide-surfactant aggregate consisting of gelatin and sodium dodecyl sulfate (SDS) in potassium dihydrogen phosphate (KP) buffer. The average solvation time (tauS) in gelatin-SDS aggregate at 45 degrees C is found to be 1780 ps, which is about 13 times slower than that in 15 mM SDS in KP buffer at the same temperature. The fluorescence anisotropy decay in gelatin-SDS aggregate is also different from that in SDS micelles in KP buffer. DCM displays negligible emission in the presence of gelatin in aqueous solution. Thus the solvation dynamics in the presence of gelatin and SDS is exclusively due to the probe (DCM) molecules at the gelatin-micelle interface. The slow solvation dynamics is ascribed to the restrictions imposed on the water molecules trapped between the polypeptide chain and micellar aggregates. The critical association concentration (cac) of SDS for gelatin is determined to be 0.5 +/- 0.1 mM.

  17. Mechanism of formation of metal sulfide ultrafine particles in reverse micelles using a gas injection method

    Sato, Hiroshi; Tsubaki, Yoritaka; Hirai, Takayuki; Komasawa, Isao [Osaka Univ., Toyonaka, Osaka (Japan)


    The mechanism of formation of ultrafine CdS, ZnS, and their composite particles by the injection of H{sub 2}S into reverse micelles was studied. The particle formation process was followed by the change in UV-visible absorption spectra. The kinetics of the whole process including dissolution of H{sub 2}S, nucleation, particle growth, and coagulation was analyzed from time-course changes of the size and number of formed particles. The dissolution of H{sub 2}S was the principal rate-determining step, and most of the dissolved H{sub 2}S was consumed for particle growth. The particles formed in the present gas injection method were larger in size than those in the previous solution-mixing method in most cases. A kinetic scheme based on the distribution of the species among the micelles was then proposed, and this successfully explained the particle growth. Composite particles of CdS and ZnS having mixed crystal or core-shell structures were also prepared, and the application of these particles as photocatalysts for the cleavage of water to generate H{sub 2} was then investigated.

  18. Non-Equilibrium Dynamics of Vesicles and Micelles by Self-Assembly of Block Copolymers with Double Thermoresponsivity

    Tang, Yu-Hang; Li, Zhen; Li, Xuejin; Deng, Mingge; Karniadakis, George Em


    We present a mesoscopic simulation study of doubly thermoresponsive self-assemblies, revealing previously unknown dynamic behavior and proving experimental hypotheses. By explicitly modeling internal energy as a degree of freedom of coarse-grained particles, we simulated the thermally induced self assembly process triggered by the evolution of temperature over time and space. We found that both external and intrinsic factors are responsible for altering the assembly pathway of thermoresponsive micelles and hence determining the final aggregate morphology. We identified a frequency regime where thermoresponsive unilamellar vesicles can sustain repeated heating cooling cycles in a thermal loading test, and we quantified the collapse probability and half-life of the vesicles under frequencies that cause vesicle destruction. Two molecular movement modes dominate, namely flip and slip, in thermoresponsive bilayer membranes during the inversion of composition. We demonstrated that doubly thermoresponsive micelles and vesicles, as potential drug delivery vehicles, exhibit distinct hydrodynamic behavior when flowing through capillaries whose temperature spans across the inversion temperature of the carriers.

  19. Recycled aggregates concrete: aggregate and mix properties

    González-Fonteboa, B.


    Full Text Available This study of structural concrete made with recycled concrete aggregate focuses on two issues: 1. The characterization of such aggregate on the Spanish market. This involved conducting standard tests to determine density, water absorption, grading, shape, flakiness and hardness. The results obtained show that, despite the considerable differences with respect to density and water absorption between these and natural aggregates, on the whole recycled aggregate is apt for use in concrete production. 2. Testing to determine the values of basic concrete properties: mix design parameters were established for structural concrete in non-aggressive environments. These parameters were used to produce conventional concrete, and then adjusted to manufacture recycled concrete aggregate (RCA concrete, in which 50% of the coarse aggregate was replaced by the recycled material. Tests were conducted to determine the physical (density of the fresh and hardened material, water absorption and mechanical (compressive strength, splitting tensile strength and modulus of elasticity properties. The results showed that, from the standpoint of its physical and mechanical properties, concrete in which RCA accounted for 50% of the coarse aggregate compared favourably to conventional concrete.

    Se aborda el estudio de hormigones estructurales fabricados con áridos reciclados procedentes de hormigón, incidiéndose en dos aspectos: 1. Caracterización de tales áridos, procedentes del mercado español. Para ello se llevan a cabo ensayos de densidad, absorción, granulometría, coeficiente de forma, índice de lajas y dureza. Los resultados obtenidos han puesto de manifiesto que, a pesar de que existen diferencias notables (sobre todo en cuanto a densidad y absorción con los áridos naturales, las características de los áridos hacen posible la fabricación de hormigones. 2. Ensayos sobre propiedades básicas de los hormigones: se establecen parámetros de dosificaci

  20. Protein Colloidal Aggregation Project

    Oliva-Buisson, Yvette J. (Compiler)


    To investigate the pathways and kinetics of protein aggregation to allow accurate predictive modeling of the process and evaluation of potential inhibitors to prevalent diseases including cataract formation, chronic traumatic encephalopathy, Alzheimer's Disease, Parkinson's Disease and others.

  1. Aggregation and Averaging.

    Siegel, Irving H.

    The arithmetic processes of aggregation and averaging are basic to quantitative investigations of employment, unemployment, and related concepts. In explaining these concepts, this report stresses need for accuracy and consistency in measurements, and describes tools for analyzing alternative measures. (BH)

  2. Radiolabeling of liposomes and polymeric micelles with PET-isotopes

    Ingemann Jensen, A.T.


    This thesis is divided into three separate chapters that can be read independently. Chapter 1 is a general introduction, touching upon liposomes and polymeric micelles and radiolabeling with 18F and 64Cu. Chapter 2 and 3 address two separate research projects, each described below. A complete reference list is compiled in the end, immediately after the three chapters. This is followed by the supplementary information, divided into appropriate sections. Finally, the two first-authored manuscripts are attached as appendices. Chapter 1. The field of nanoparticulate drug delivery has been hailed as a revolution in modern therapeutics, especially in chemotherapy. A major reason is the ability of nanoparticles to accumulate in tumor tissue. Liposomes are the classic nanoparticle, consisting of a lipid membrane with an aqueous core. Polymeric micelles are made from amphiphilic detergent-like copolymers, that self-assemble in water. Therapy with nanoparticles is hampered by often poor tumor accumulation, combined with massive uptake by macrophages in the liver and spleen. For this reason, visualizing nanoparticle pharmacokinetics in-vivo is a valuable tool in the on-going research. Such visualization can be done by labeling with radio isotopes. Isotopes that emit positrons (PET-isotopes) can be detected by PET (positron emission tomography) technology, an accurate technique that has gained popularity in recent years. PET-isotopes of interest include 18F and 64Cu. In addition to being a research tool, radiolabeled nanoparticles hold promise as a radiopharmaceutical in themselves, as a means of imaging tumor tissue, aiding in diagnosis and surgery. Chapter 2. A method for labeling liposomes with 18F (97% positron decay, T = 110 min) was investigated. 18F is widely available, but is hampered by a short half-life only allowing up to 8 hours scans. 18F must be covalently attached to components of the liposome. By binding to a lipid, it can be stably lodged in the membrane. A

  3. Cell aggregation and sedimentation.

    Davis, R H


    The aggregation of cells into clumps or flocs has been exploited for decades in such applications as biological wastewater treatment, beer brewing, antibiotic fermentation, and enhanced sedimentation to aid in cell recovery or retention. More recent research has included the use of cell aggregation and sedimentation to selectively separate subpopulations of cells. Potential biotechnological applications include overcoming contamination, maintaining plasmid-bearing cells in continuous fermentors, and selectively removing nonviable hybridoma cells from perfusion cultures.

  4. Interactions of phenol with cationic micelles of hexadecyltrimethylammonium bromide studied by titration calorimetry, conductimetry, and 1H NMR in the range of low additive and surfactant concentrations.

    Chaghi, Radhouane; de Ménorval, Louis-Charles; Charnay, Clarence; Derrien, Gaëlle; Zajac, Jerzy


    Interactions of phenol (PhOH) with micellar aggregates of hexadecyltrimethylammonium bromide (HTAB) in aqueous solutions at surfactant concentrations close to the CMC and phenol contents of 1, 5, or 10 mmol kg(-1) have been investigated at 303 K by means of titration calorimetry, solution conductimetry, and (1)H NMR spectroscopy. Estimates of the main thermodynamic parameters related to HTAB micellization were made for PhOH/HTAB/H(2)O systems based on the specific conductivity measurements and calorimetric determination of the cumulative enthalpy of dilution as functions of the surfactant concentration at a fixed additive content. The combined analysis of the results obtained in H(2)O solutions pointed to the preferential location of PhOH in the outer micelle parts by an enthalpy-driven mechanism. Additional PhOH molecules were located increasingly deeper within the micelle core. The (1)H NMR study of PhOH solubilization by 1.5 mmol kg(-1) HTAB solutions in D(2)O indicated that the two categories of the solubilization site became saturated with the solubilizate already at the lowest additive content. Dissimilar amounts of the solubilized material in H(2)O and D(2)O solutions were ascribed to the difference in the initial micelle structures formed in the two solvents, as inferred from calorimetry and (1)H NMR studies of the HTAB micellization in D(2)O and H(2)O.

  5. π-π Stacking induced enhanced molecular solubilization, singlet oxygen production, and retention of a photosensitizer loaded in thermosensitive polymeric micelles.

    Shi, Yang; Elkhabaz, Ahmed; Yengej, Fjodor A Yousef; van den Dikkenberg, Joep; Hennink, Wim E; van Nostrum, Cornelus F


    Cancer photodynamic therapy (PDT) by photosensitizers (PS)-loaded polymeric micelles (PM) is hampered by the tendency of PS to aggregate in PM and/or by premature release of PS in the blood circulation. In the present study, aromatic thermosensitive PM, characterized by π-π stacking interaction, are used to encapsulate an axially solketal-substituted silicon phthalocyanine (Si(sol)2 Pc) with enhanced loading capacity, smaller size, and significantly improved retention of Si(sol)2 Pc compared with systems based on thermosensitive PM lacking aromatic groups. Interestingly, Si(sol)2 Pc is much less prone to aggregation in the aromatic PM, i.e., the amount of Si(sol)2 Pc that could be encapsulated without aggregation is 330 times higher in the aromatic PM than in the nonaromatic PM. Furthermore, Si(sol)2 Pc in the aromatic PM in a molecularly dissolved (non-aggregated) form displays three times more efficient singlet oxygen production than Si(sol)2 Pc aggregated in the non-aromatic PM. As a result, the photocytotoxicity of Si(sol)2 Pc-loaded aromatic PM to B16F10 cells is increased, compared with that of the non-aromatic PM, while no significant cytotoxicity is observed in the dark. Fluorescence-activated cell sorting (FACS) and confocal laser scanning microscopy (CLSM) analysis shows cell uptake of Si(sol)2 Pc loaded in the aromatic PM, and the Si(sol)2 Pc is taken up by the cells together with the micelles. The efficient singlet oxygen production of Si(sol)2 Pc dissolved in the aromatic PM makes it an interesting formulation for cancer PDT.

  6. Familial aggregation and childhood blood pressure.

    Wang, Xiaoling; Xu, Xiaojing; Su, Shaoyong; Snieder, Harold


    There is growing concern about elevated blood pressure (BP) in children. The evidence for familial aggregation of childhood BP is substantial. Twin studies have shown that a large part of the familial aggregation of childhood BP is due to genes. The first part of this review provides the latest progress in gene finding for childhood BP, focusing on the combined effects of multiple loci identified from the genome-wide association studies on adult BP. We further review the evidence on the contribution of the genetic components of other family risk factors to the familial aggregation of childhood BP including obesity, birth weight, sleep quality, sodium intake, parental smoking, and socioeconomic status. At the end, we emphasize the promise of using genomic-relatedness-matrix restricted maximum likelihood (GREML) analysis, a method that uses genome-wide data from unrelated individuals, in answering a number of unsolved questions in the familial aggregation of childhood BP.

  7. Active matter model of Myxococcus xanthus aggregation

    Patch, Adam; Bahar, Fatmagul; Liu, Guannan; Thutupalli, Shashi; Welch, Roy; Yllanes, David; Shaevitz, Joshua; Marchetti, M. Cristina

    Myxococcus xanthus is a soil-dwelling bacterium that exhibits several fascinating collective behaviors including streaming, swarming, and generation of fruiting bodies. A striking feature of M. xanthus is that it periodically reverses its motility direction. The first stage of fruiting body formation is characterized by the aggregation of cells on a surface into round mesoscopic structures. Experiments have shown that this aggregation relies heavily on regulation of the reversal rate and local mechanical interactions, suggesting motility-induced phase separation may play an important role. We have adapted self-propelled particle models to include cell reversal and motility suppression resulting from sporulation observed in aggregates. Using 2D molecular dynamics simulations, we map the phase behavior in the space of Péclet number and local density and examine the kinetics of aggregation for comparison to experiments.

  8. Two distinct mechanisms of vesicle-to-micelle and micelle-to-vesicle transition are mediated by the packing parameter of phospholipid-detergent systems

    Stuart, Marc C. A.; Boekema, Egbert J.


    The detergent solubilization and reformation of phospholipid vesicles was studied for various detergents. Two distinct mechanisms of vesicle-to-micelle and micelle-to-vesicle transition were observed by turbidimetry and cryo-electron microscopy. The first mechanism involves fast solubilization of ph

  9. Diketopyrrolopyrrole Amphiphile-Based Micelle-Like Fluorescent Nanoparticles for Selective and Sensitive Detection of Mercury(II) Ions in Water.

    Nie, Kaixuan; Dong, Bo; Shi, Huanhuan; Liu, Zhengchun; Liang, Bo


    A technique for encapsulating fluorescent organic probes in a micelle system offers an important alternative method to manufacture water-soluble organic nanoparticles (ONPs) for use in sensing Hg(2+). This article reports on a study of a surfactant-free micelle-like ONPs based on a 3,6-di(2-thienyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (TDPP) amphiphile, (2-(2-(2-methoxyethoxy)ethyl)-3,6-di(2-thiophyl)-2,5-dihydropyrrolo[3,4-c]pyrrole-1,4-dione (NDPP) fabricated to monitor Hg(2+) in water. NDPP was synthesized through a simple one-step modification of a commercially available dye TDPP with a flexible and hydrophilic alkoxy. This study reports, for the first time, that TDPP dyes can respond reversibly, sensitively, and selectively to Hg(2+) through TDPP-Hg-TDPP complexation, similar to the well-known thymine(T)-Hg-thymine(T) model and the accompanying molecular aggregation. Interestingly, transmission electron microscopy (TEM) and dynamic light scattering (DLS) confirmed that, in water, NDPP forms loose micelle-like fluorescent ONPs with a hydrohobic TDPP portion encapsulated inside. These micelle-like nanoparticles offer an ideal location for TDPP-Hg complexation with a modest molecular aggregation, thereby providing both clear visual and spectroscopic signals for Hg(2+) sensing. An estimated detection limit of 11 nM for Hg(2+) sensing with this NDPP nanoparticle was obtained. In addition, NDPP ONPs show good water solubility and high selectivity to Hg(2+) in neutral or alkalescent water. It was superior to most micelle-based nanosensors, which require a complicated process in the selection or synthesis of suitable surfactants. The determinations in real samples (river water) were made and satisfactory results were achieved. This study provides a low-cost strategy for fabricating small molecule-based fluorescent nanomaterials for use in sensing Hg(2+). Moreover, the NDPP nanoparticles show potential ability in Hg(2+) ion adsorption and recognization of

  10. Formation of wormlike micelles in anionic surfactant AES aqueous solutions


    The growth and structure of anionic micelles of sodium dodecyl trioxyethylene sulfate (AES) in the presence 3+of multivalent counterion Al were investigated by means of dynamic rheological methods. It has been obtained by the measurements of shear viscosity, complex viscosity and dynamic moduli, as well as the application of Cox-Merz rule and Cole-Cole plot that wormlike micelle and network structure could be formed in AES/AlCl3 aqueous solutions.The structure was of a character of nonlinear viscoelastic fluid and departure from the simple Maxwell model. The technique of freeze-fracture transmission electron microscopy (FF-TEM) was also used to confirm the formation of this interesting structure.``

  11. Estimation of interfacial acidity of sodium dodecyl sulfate micelles

    Arghya Dey; G Naresh Patwari


    An enhancement in the excited state proton transfer (ESPT) processes of coumarin-102 (C-102) dye was observed upon addition of salicylic acid and hydrochloric acid in sodium dodecyl sulfate (SDS) micellar solution. The phenomenon was observed only in the micellar medium of anionic surfactant SDS and not in case of cationic (CTAB) or neutral (Trition X -100) surfactants. ESPT of C-102 was also observed in aqueous solutions but on addition of very high concentrations of hydrochloric acid. However, on comparing the ratio of the protonated species from the emission spectra in the presence and absence of SDS micelle, a conclusive estimation of the local proton concentration at the Stern layer of SDS micelles could be evaluated.

  12. Large magnetic anisotropy in ferrihydrite nanoparticles synthesized from reverse micelles

    Duarte, E L [Instituto de Fisica, Universidade de Sao Paulo, CP 66318, Sao Paulo, 05315-970 (Brazil); Itri, R [Instituto de Fisica, Universidade de Sao Paulo, CP 66318, Sao Paulo, 05315-970 (Brazil); Jr, E Lima [Instituto de Fisica, Universidade de Sao Paulo, CP 66318, Sao Paulo, 05315-970 (Brazil); Baptista, M S [Instituto de Quimica, Universidade de Sao Paulo, Avenida Professor Lineu Prestes 748, Sao Paulo (Brazil); Berquo, T S [Institute for Rock Magnetism, University of Minnesota, 100 Union Street SE, Minneapolis, MN 55455-0128 (United States); Goya, G F [Instituto de Nanociencias de Aragon (INA), Universidad de Zaragoza, Pedro Cerbuna 12 (50009), Zaragoza (Spain)


    Six-line ferrihydrite (FH) nanoparticles have been synthesized in the core of reverse micelles, used as nanoreactors to obtain average particle sizes {approx} 2-4 nm. The blocking temperatures T{sub B}{sup m} extracted from magnetization data increased from {approx}10 to 20 K for increasing particle size. Low-temperature Moessbauer measurements allowed us to observe the onset of differentiated contributions from the particle core and surface as the particle size increases. The magnetic properties measured in the liquid state of the original emulsion showed that the ferrihydrite phase is not present in the liquid precursor, but precipitates in the micelle cores after the free water is freeze-dried. Systematic susceptibility {chi}{sub ac}(f,T) measurements showed the dependence of the effective magnetic anisotropy energies E{sub a} with particle volume, and yielded an effective anisotropy value of K{sub eff} = 312 {+-} 10 kJ m{sup -3}.

  13. Highly ordered binary assembly of silica mesochannels and surfactant micelles for extraction and electrochemical analysis of trace nitroaromatic explosives and pesticides.

    Yan, Fei; He, Yayun; Ding, Longhua; Su, Bin


    The rapid and sensitive detection of nitroaromatic compounds is of great significance for human health, the environment, and public security. The present work reports on the extraction and electrochemical analysis of trace nitroaromatic compounds, such as explosives and organophosphate pesticides (OPs), using the indium tin oxide (ITO) electrodes modified with a highly ordered and aligned binary assembly of silica mesochannels and micelles (BASMM). With a pore diameter of ca. 2-3 nm, silica mesochannels (SMs) perpendicularly oriented to the ITO electrode surface can provide hard and robust supports to confine the soft cylindrical micelles formed by the aggregation of cationic surfactants, namely, cetyltrimethylammonium bromide (CTAB). Due to the organized self-assembly of hydrocarbon tails of CTAB surfactants, each micelle has a hydrophobic core, which acts as an excellent adsorbent for rapid extraction and preconcentration of trace nitroaromatic compounds from aqueous solutions via the hydrophobic effect. Furthermore, the cylindrical micelles are directly in contact with the underlying electrode surface, to which extracted compounds can freely diffuse and then be reduced therein, thus allowing their determination by means of voltammetry. Using the BASMM/ITO sensor, electrochemical analysis of trace nitroaromatic explosives, including 2,4,6-trinitrotoluene (TNT), 2,4,6-trinitrophenol, 2,6-dinitrotoluene, 3-nitrophenol, and nitrobenzene, and OPs, such as paraoxon, methyl parathion, and fenitrothion, was achieved with a fast response, wide linear range, high sensitivity, and low detection limit at the ppb level. TNT and paraoxon in real apple, tea, and water samples were also determined. By combining the heterogeneous extraction and determination in one ordered binary nanostructure, the BASMM sensor provides a very simple, rapid, and cost-effective way for analysis of nitroaromatic compounds and can be extended to a wide range of lipophilic yet redox-active analytes.

  14. The role of aggregate formation in solvent extraction of calcium

    Gaonkar, A.G.; Neuman, R.D.


    In solvent extraction processes involving hydrometallurgical separations, spent nuclear fuel reprocessing, and nuclear waste processing operations, metal ions transfer across the boundary between two immiscible liquids. Hence, the properties of the liquid/liquid interface can often influence the extraction process. This suggests that one, therefore, should be able to control the extraction rate by proper manipulation of the nature of the liquid/liquid interface. In an earlier communication (1) from this laboratory, aggregates, possibly reversed micelles, were proposed to form in the system di(2-ethylhexyl)phosphoric acid (HDEHP)/n-hexane/CaCl/sub 2/ solution under certain conditions. The objective of the present study was to determine whether the amount of calcium extracted and the rate of extraction become significant when reversed micelles form. The interfacial tension (..gamma..), equilibrium distribution coefficient (K/sub d/), and mass transfer coefficient (k/sub ao/) were obtained for the system HDEHP/n-hexane/0.01 mol dm/sup -3/ CaCl/sub 2/ solution. 11 refs., 4 figs.

  15. Biosensors with reversed micelle-enzyme sensitive membrane


    The effect of reversed micelle on the conformation of enzyme was studied by sensor techniques. By means of measurement of the response current of GOD enzyme membrane electrode, the effects of enzyme embedded in AOT reversed micellar on GOD conformation and catalytic activity are discussed. The results show that the response current increased greatly with decreasing ratio of GOD/AOT, meaning that the catalytic activity and the conformation stability of enzyme were enhanced.

  16. Optical dynamics of molecular aggregates

    de Boer, Steven


    The subject of this thesis is the spectroscopy and dynamics of molecular aggregates in amorphous matrices. Aggregates of three different molecules were studied. The molecules are depicted in Fig. (1.1). Supersaturated solutions of these molecules show aggregate formation. Aggregation is a process si

  17. Gold-Loaded Polymeric Micelles with Temperature-Modulated Catalytic Activity

    HU Na; SHI Dongjian; LI Jihang; LI Junfeng; CHEN Mingqing


    Four-armed amphiphilic block copolymers, polystyrene-b-poly(N-isopropylacrylamide) (PS-b-PNIPAM)4, were synthesized by atom transfer radical polymerization (ATRP). (PS-b-PNIPAM)4 self-assembled into micelles with PS block as core and thermoresponsive PNIPAM block as corona. The gold nanoparticles (Au NPs) with average diameter about 5.8 nm were immobilized on the surfaces of the micelles by the reduction of the corresponding ions. The micelle-supported gold nanoparticles (Au-micelles) were applied to catalyze the reduction ofp-nitrophenol. Moreover, the activity of the Au-micelle catalyst could be modulated by the temperature and the Au-micelles could be easily recovered by changing the temperature and recycled four times with high catalytic activity.

  18. Construction of the Active Site of Metalloenzyme on Au NC Micelles

    ZHANG, Zhiming; FU, Qiuan; HUANG, Xin; XU, Jiayun; LIU, Junqiu; SHEN, Jiacong


    For developing an efficient nanoenzyme system with self-assembly strategy, gold nanocrystal micelles (Au NC micelles) with inserted catalytic Zn(Ⅱ) centers were constructed by self-assembly of a catalytic ligand [N,N-bis(2-aminoethyl)-N'dodecylethylenediamine] Zn(Ⅱ) complexes (Zn(Ⅱ)L) on the surface of Au NC via hy- drophobic interaction. The functionalized Au NC micelles acted as an excellent nanoenzyme model for imitating ribonuclease. The catalytic capability of the Au NC micelles was evaluated by accelerating the cleavage of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP). These functionalized Au NC micelles exhibited considerable ri- bonuclease-like activities by a factor of 4.9×104 (kcat/kuncat) for the cleavage of HPNP in comparison to the sponta- neous cleavage of HPNP at 37℃. The catalytic capability of the functionalized Au NC micelles can be considera- bly compared to other models reported previously as nanoenzymes under the comparable conditions.

  19. Development of the simple and sensitive method for lipoxygenase assay in AOT/isooctane reversed micelles.

    Park, Kyung Min; Kim, Yu Na; Choi, Seung Jun; Chang, Pahn-Shick


    In this study, we investigated the possibility of reversed micelles, widely used as an enzyme reactor for lipases, for the determination of lipoxygenase activity. Although it is rapid and simple, reversed micelles have some limitations, such as interference by UV-absorbing materials and surfactant. Lipoxygenase activity in the reversed micelles was determined by reading the absorbance of the lipid hydroperoxidation product (conjugated diene) at 234 nm. Among surfactants and organic media, AOT and isooctane were most effective for the dioxygenation of linoleic acid in reversed micelles. The strong absorbance of AOT in the UV region is a major obstacle for the direct application of the AOT/isooctane reversed micelles to lipoxygenase activity determination. To prevent interference by AOT, we added an AOT removal step in the procedure for lipoxygenase activity determination in reversed micelles. The lipoxygenase activity was dependent on water content, and maximum activity was obtained at an R-value of 10.

  20. Observing Convective Aggregation

    Holloway, Christopher E.; Wing, Allison A.; Bony, Sandrine; Muller, Caroline; Masunaga, Hirohiko; L'Ecuyer, Tristan S.; Turner, David D.; Zuidema, Paquita


    Convective self-aggregation, the spontaneous organization of initially scattered convection into isolated convective clusters despite spatially homogeneous boundary conditions and forcing, was first recognized and studied in idealized numerical simulations. While there is a rich history of observational work on convective clustering and organization, there have been only a few studies that have analyzed observations to look specifically for processes related to self-aggregation in models. Here we review observational work in both of these categories and motivate the need for more of this work. We acknowledge that self-aggregation may appear to be far-removed from observed convective organization in terms of time scales, initial conditions, initiation processes, and mean state extremes, but we argue that these differences vary greatly across the diverse range of model simulations in the literature and that these comparisons are already offering important insights into real tropical phenomena. Some preliminary new findings are presented, including results showing that a self-aggregation simulation with square geometry has too broad distribution of humidity and is too dry in the driest regions when compared with radiosonde records from Nauru, while an elongated channel simulation has realistic representations of atmospheric humidity and its variability. We discuss recent work increasing our understanding of how organized convection and climate change may interact, and how model discrepancies related to this question are prompting interest in observational comparisons. We also propose possible future directions for observational work related to convective aggregation, including novel satellite approaches and a ground-based observational network.

  1. Predicting proton titration in cationic micelle and bilayer environments

    Morrow, Brian H.; Shen, Jana K. [Department of Pharmaceutical Sciences, University of Maryland, Baltimore, Maryland 21201 (United States); Eike, David M.; Murch, Bruce P.; Koenig, Peter H. [Computational Chemistry, Modeling and Simulation GCO, Procter and Gamble, Cincinnati, Ohio 45201 (United States)


    Knowledge of the protonation behavior of pH-sensitive molecules in micelles and bilayers has significant implications in consumer product development and biomedical applications. However, the calculation of pK{sub a}’s in such environments proves challenging using traditional structure-based calculations. Here we apply all-atom constant pH molecular dynamics with explicit ions and titratable water to calculate the pK{sub a} of a fatty acid molecule in a micelle of dodecyl trimethylammonium chloride and liquid as well as gel-phase bilayers of diethyl ester dimethylammonium chloride. Interestingly, the pK{sub a} of the fatty acid in the gel bilayer is 5.4, 0.4 units lower than that in the analogous liquid bilayer or micelle, despite the fact that the protonated carboxylic group is significantly more desolvated in the gel bilayer. This work illustrates the capability of all-atom constant pH molecular dynamics in capturing the delicate balance in the free energies of desolvation and Coulombic interactions. It also shows the importance of the explicit treatment of ions in sampling the protonation states. The ability to model dynamics of pH-responsive substrates in a bilayer environment is useful for improving fabric care products as well as our understanding of the side effects of anti-inflammatory drugs.

  2. Polymeric micelles encapsulating photosensitizer: structure/photodynamic therapy efficiency relation.

    Gibot, Laure; Lemelle, Arnaud; Till, Ugo; Moukarzel, Béatrice; Mingotaud, Anne-Françoise; Pimienta, Véronique; Saint-Aguet, Pascale; Rols, Marie-Pierre; Gaucher, Mireille; Violleau, Frédéric; Chassenieux, Christophe; Vicendo, Patricia


    Various polymeric micelles were formed from amphiphilic block copolymers, namely, poly(ethyleneoxide-b-ε-caprolactone), poly(ethyleneoxide-b-d,l-lactide), and poly(ethyleneoxide-b-styrene). The micelles were characterized by static and dynamic light scattering, electron microscopy, and asymmetrical flow field-flow fractionation. They all displayed a similar size close to 20 nm. The influence of the chemical structure of the block copolymers on the stability upon dilution of the polymeric micelles was investigated to assess their relevance as carriers for nanomedicine. In the same manner, the stability upon aging was assessed by FRET experiments under various experimental conditions (alone or in the presence of blood proteins). In all cases, a good stability over 48 h for all systems was encountered, with PDLLA copolymer-based systems being the first to release their load slowly. The cytotoxicity and photocytotoxicity of the carriers were examined with or without their load. Lastly, the photodynamic activity was assessed in the presence of pheophorbide a as photosensitizer on 2D and 3D tumor cell culture models, which revealed activity differences between the 2D and 3D systems.

  3. Micelles and nanoparticles for ultrasonic drug and gene delivery.

    Husseini, Ghaleb A; Pitt, William G


    Drug delivery research employing micelles and nanoparticles has expanded in recent years. Of particular interest is the use of these nanovehicles that deliver high concentrations of cytotoxic drugs to diseased tissues selectively, thus reducing the agent's side effects on the rest of the body. Ultrasound, traditionally used in diagnostic medicine, is finding a place in drug delivery in connection with these nanoparticles. In addition to their non-invasive nature and the fact that they can be focused on targeted tissues, acoustic waves have been credited with releasing pharmacological agents from nanocarriers, as well as rendering cell membranes more permeable. In this article, we summarize new technologies that combine the use of nanoparticles with acoustic power both in drug and gene delivery. Ultrasonic drug delivery from micelles usually employs polyether block copolymers and has been found effective in vivo for treating tumors. Ultrasound releases drug from micelles, most probably via shear stress and shock waves from the collapse of cavitation bubbles. Liquid emulsions and solid nanoparticles are used with ultrasound to deliver genes in vitro and in vivo. The small packaging allows nanoparticles to extravasate into tumor tissues. Ultrasonic drug and gene delivery from nanocarriers has tremendous potential because of the wide variety of drugs and genes that could be delivered to targeted tissues by fairly non-invasive means.

  4. Chain exchange kinetics of block copolymer micelles in ionic liquids

    Ma, Yuanchi; Lodge, Timothy

    The chain exchange kinetics of block copolymer micelles has been studied using time-resolved small-angle neutron scattering (TR-SANS), a key tool in determining the average micelle composition in contrast-matched solvents. In this work, PMMA-block-PnBMA was selected as the model block copolymer, which has a LCST behavior in the common ionic liquids, [EMIM][TFSI] and [BMIM][TFSI]. We examined the chain exchange kinetics of three PMMA-block-PnBMA copolymers, with identical PMMA block length (MPMMA = 25000) and different PnBMA block lengths (MPnBMA = 24000, 35000 and 53000); the Flory-Huggins interaction parameter (χ) between the core (PnBMA) and the solvent were varied by mixing [EMIM][TFSI] and [BMIM][TFSI] in different ratios. We found that the relaxation of the initial segregation of h- and d- micelles followed the same form with the time as previously developed by our group. Assuming that single chain expulsion is the rate limiting step, the thermal barrier was found to depend linearly on the core block length (Ncore) . Furthermore, the effect of χ on the chain exchange kinetics will also be discussed.

  5. Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

    Dian, Linghui; Yu, Enjiang; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin


    To improve its poor aqueous solubility and stability, the potential chemotherapeutic drug quercetin was encapsulated in soluplus polymeric micelles by a modified film dispersion method. With the encapsulation efficiency over 90%, the quercetin-loaded polymeric micelles (Qu-PMs) with drug loading of 6.7% had a narrow size distribution around mean size of 79.00 ± 2.24 nm, suggesting the complete dispersibility of quercetin in water. X-ray diffraction (XRD) patterns illustrated that quercetin was in amorphous or molecular form within PMs. Fourier transform infrared spectroscopy (FTIR) indicated that quercetin formed intermolecular hydrogen bonding with carriers. An in vitro dialysis test showed the Qu-PMs possessed significant sustained-release property, and the formulation was stable for at least 6 months under accelerated conditions. The pharmacokinetic study in beagle dogs showed that absorption of quercetin after oral administration of Qu-PMs was improved significantly, with a half-life 2.19-fold longer and a relative oral bioavailability of 286% as compared to free quercetin. Therefore, these novel soluplus polymeric micelles can be applied to encapsulate various poorly water-soluble drugs towards a development of more applicable therapeutic formulations.

  6. Microwave-assisted Palladium-micelle-catalyzed Suzuki Cross-coupling Reaction in Water

    LIN Li; LI Sheng-hai; JIANG Ri-hua


    A microwave-accelerated Suzuki coupling procedure was developed via guanidinium ionic liquids(GILs)stabilized Pd-micelle.The Pd micelle/GILs play a key role in enhancing the activity,due to the highly dispersed Pd active sites and the phase transfer function of GILs,which ensures the adsorption of reactants and facilitates the translation of the intermediates to the surface of the micelle.

  7. Effect of Micelle Composition on Acidic Drugs Separation Behavior by Micellar Electrokinetic Capillary Chromatography


    Micellar electrokinetic capillary chromatography (MECC) separation of four acidic drugs similar in structure was studied. Both anionic surfactant sodium dodecyl sulfate (SDS) and nonionic surfactant Tween 20 were used to form single micelles and mixed micelles as pseudostationary phases. The effects of the composition of micellar solution on retention behaviors were studied. The results indicate that there is markedly different selectivity among SDS, Tween 20 and the mixed micelles systems.

  8. Structure of phosphate fluorosurfactant based reverse micelles in supercritical carbon dioxide

    Senapati, S; Keiper, J. S.; de Simone, J. M.; Wignall, G. D.; Melnichenko, Y. B.; Frielinghaus, H; Berkowitz, M. L.


    The existence of microemulsions in the system composed of phosphate-based fluorosurfactant, water, and supercritical CO2 is demonstrated by small-angle neutron scattering experiments. A computer simulation study performed on a reverse micelle created in this system shows that the micelle remains stable over a 4 ns time period of the simulation. While the data obtained from the experiments provide information about the size of the reverse micelle, the data obtained from the simulations provide...

  9. How to Squeeze a Sponge: Casein Micelles under Osmotic Stress, a SAXS Study

    Bouchoux, Antoine; Gésan-Guiziou, Geneviève; Pérez, Javier; Cabane, Bernard


    By combining the osmotic stress technique with small-angle x-ray scattering measurements, we followed the structural response of the casein micelle to an overall increase in concentration. When the aqueous phase that separates the micelles is extracted, they behave as polydisperse repelling spheres and their internal structure is not affected. When they are compressed, the micelles lose water and shrink to a smaller volume. Our results indicate that this compression is nonaffine, i.e., some p...

  10. A Trimeric Surfactant: Surface Micelles, Hydration-Lubrication, and Formation of a Stable, Charged Hydrophobic Monolayer.

    Kampf, Nir; Wu, Chunxian; Wang, Yilin; Klein, Jacob


    The surface structure of the trimeric surfactant tri(dodecyldimethylammonioacetoxy)diethyltriamine trichloride (DTAD) on mica and the interactions between two such DTAD-coated surfaces were determined using atomic force microscopy and a surface force balance. In an aqueous solution of 3 mM, 5 times the critical aggregation concentration (CAC), the surfaces are coated with wormlike micelles or hemimicelles and larger (∼80 nm) bilayer vesicles. Repulsive normal interactions between the surfaces indicate a net surface charge and a solution concentration of ions close to that expected from the CAC. Moreover, this surface coating is strongly lubricating up to some tens of atmospheres, attributed to the hydration-lubrication mechanism acting at the exposed, highly hydrated surfactant headgroups. Upon replacement of the DTAD solution with surfactant-free water, the surface structures have changed on the DTAD monolayers, which then jump into adhesive contact on approach, both in water and following addition of 0.1 M NaNO3. This trimeric surfactant monolayer, which is highly hydrophobic, is found to be positively charged, which is evident from the attraction between the DTAD monolayer and negatively charged bare mica across water. These monolayers are stable over days even under a salt solution. The stability is attributed to the several stabilization pathways available to DTAD on the mica surface.

  11. NMR Structures and Interactions of Temporin-1Tl and Temporin-1Tb with Lipopolysaccharide Micelles

    Bhunia, Anirban; Saravanan, Rathi; Mohanram, Harini; Mangoni, Maria L.; Bhattacharjya, Surajit


    Temporins are a group of closely related short antimicrobial peptides from frog skin. Lipopolysaccharide (LPS), the major constituent of the outer membrane of Gram-negative bacteria, plays important roles in the activity of temporins. Earlier studies have found that LPS induces oligomerization of temporin-1Tb (TB) thus preventing its translocation across the outer membrane and, as a result, reduces its activity on Gram-negative bacteria. On the other hand, temporin-1Tl (TL) exhibits higher activity, presumably because of lack of such oligomerization. A synergistic mechanism was proposed, involving TL and TB in overcoming the LPS-mediated barrier. Here, to gain insights into interactions of TL and TB within LPS, we investigated the structures and interactions of TL, TB, and TL+TB in LPS micelles, using NMR and fluorescence spectroscopy. In the context of LPS, TL assumes a novel antiparallel dimeric helical structure sustained by intimate packing between aromatic-aromatic and aromatic-aliphatic residues. By contrast, independent TB has populations of helical and aggregated conformations in LPS. The LPS-induced aggregated states of TB are largely destabilized in the presence of TL. Saturation transfer difference NMR studies have delineated residues of TL and TB in close contact with LPS and enhanced interactions of these two peptides with LPS, when combined together. Fluorescence resonance energy transfer and 31P NMR have pointed out the proximity of TL and TB in LPS and conformational changes of LPS, respectively. Importantly, these results provide the first structural insights into the mode of action and synergism of antimicrobial peptides at the level of the LPS-outer membrane. PMID:21586570

  12. Micelle swelling agent derived cavities for increasing hydrophobic organic compound removal efficiency by mesoporous micelle@silica hybrid materials

    Shi, Yifeng


    Mesoporous micelle@silica hybrid materials with 2D hexagonal mesostructures were synthesized as reusable sorbents for hydrophobic organic compounds (HOCs) removal by a facile one-step aqueous solution synthesis using 3-(trimethoxysily)propyl-octadecyldimethyl-ammonium chloride (TPODAC) as a structure directing agent. The mesopores were generated by adding micelle swelling agent, 1,3,5-trimethyl benzene, during the synthesis and removing it afterward, which was demonstrated to greatly increase the HOC removal efficiency. In this material, TPODAC surfactant is directly anchored on the pore surface of mesoporous silica via SiOSi covalent bond after the synthesis due to its reactive Si(OCH 3) 3 head group, and thus makes the synthesized materials can be easily regenerated for reuse. The obtained materials show great potential in water treatment as pollutants sorbents. © 2011 Elsevier Inc. All rights reserved.

  13. Structure formation in binary mixtures of surfactants: vesicle opening-up to bicelles and octopus-like micelles

    Noguchi, Hiroshi

    Micelle formation in binary mixtures of surfactants is studied using a coarse-grained molecular simulation. When a vesicle composed of lipid and detergent types of molecules is ruptured, a disk-shaped micelle, the bicelle, is typically formed. It is found that cup-shaped vesicles and bicelles connected with worm-like micelles are also formed depending on the surfactant ratio and critical micelle concentration. The obtained octopus shape of micelles agree with those observed in the cryo-TEM images reported in [S. Jain and F. S. Bates, Macromol. 37, 1511 (2004).]. Two types of connection structures between the worm-like micelles and the bicelles are revealed.

  14. An Identity Based Aggregate Signature from Pairings

    Yike Yu


    Full Text Available An aggregate signature is a useful digital signature that supports aggregation: Given n signatures on n distinct messages from n distinct users, aggregate signature scheme is possible to aggregate all these signature into a single short signature. This single signature, along with the n original messages will convince any verifier that the n users did indeed sign the n original messages respectively (i.e., for i=1,...,n user i signed message  mi. In this paper, we propose an identity based aggregate signature scheme which requires constant pairing operations in the verification and the size of aggregate signature is independent of the number of signers. We prove that the proposed signature scheme is secure against existential forgery under adaptively chosen message and identity attack in the random oracle model assuming the intractability of the computational Diffie-Hellman problem.

  15. Polymer micelles for delayed release of therapeutics from drug-releasing surfaces with nanotubular structures.

    Sinn Aw, Moom; Addai-Mensah, Jonas; Losic, Dusan


    A new approach to engineer a local drug delivery system with delayed release using nanostructured surface with nanotube arrays is presented. TNT arrays electrochemically generated on a titanium surface are used as a model substrate. Polymer micelles as drug carriers encapsulated with drug are loaded at the bottom of the TNT structure and their delayed release is obtained by loading blank micelles (without drug) on the top. The delayed and time-controlled drug release is successfully demonstrated by controlling the ratio of blank and drug loaded-micelles. The concept is verified using four different polymer micelles (regular and inverted) loaded with water-insoluble (indomethacin) and water-soluble drugs (gentamicin).

  16. Rheological properties of novel viscoelastic micelle systems containing anionic-nonionic dimeric surfactant

    方波; 曹丹红; 江体乾


    The viscoelastic micelle systems formed by novel anionic-nonionic dimeric surfactant and conventional cationic surfactant cetyltrimethylammonium(1631) were studied.The viscoelasticity,thixotropy,flow curves and constitutive equation for the novel viscoelastic micelle systems were investigated.The results show that the micelle systems possess viscoelasticity,thixotropy,and shear thinning property.Some micelle systems possess hysteresis loops showing both viscoelasticity and thixotropy.It is proved that the flow curves are characterized by the co-rotational Jeffreys constitutive equation correctly.


    Chen Guo; Hao Wen; Huizhou Liu


    In this paper we review our work on self-assembly of the system, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) block copolymers, which is a kind of macromolecular complex fluids. The control of self-assembly could be obtained by adding inorganic salts or aliphatic alcohols. By self-assembly of amphiphilic block copolymers, a microemulsion phase is formed, which could be applied in micelle extraction, such as hollow-fiber membrane micelle extraction, magnetic micelle extraction and immobilized micelle extraction.

  18. Naturally derived micelles for rapid in vitro screening of potential cholesterol-lowering bioactives.

    Kirana, Chandra; Rogers, Paul F; Bennett, Louise E; Abeywardena, Mahinda Y; Patten, Glen S


    A high plasma cholesterol level, especially low-density lipoprotein cholesterol, indicates increased risk of cardiovascular diseases. Plasma cholesterol levels are influenced by diet and cholesterol biosynthesis, uptake, and secretion. Cholesterol uptake involves solubilization into complex phospholipid spherical bodies termed micelles that facilitate the transport of lipids through the gut brush border membrane into enterocytes. In vitro assays reported to date to determine potential cholesterol-lowering effects of various compounds require artificial micelle preparations that are elaborate and time-consuming to prepare. The aims of this study were to compare the efficacy of artificially prepared micelles with naturally derived micelles from pig's bile and to test their ability to assess potential inhibitors of cholesterol uptake. The suitability of pig's bile-derived micelles was tested both at the level of the micelle and at cellular uptake using cultured Caco-2 cells. Known cholesterol uptake inhibitors at the micelle (green tea catechins) and at the Caco-2 cell (beta-lactoglobulin-derived peptide, IIAEK) were used as reference inhibitory compounds. It was concluded that pig's bile was a rapid, reproducible, convenient, and cost-effective source of micelles for cholesterol micelle solubility and cellular uptake assay systems and is suitable for screening purposes focused on identifying potential cholesterol-lowering agents.

  19. Kinetic analysis of hydrogen production using anaerobic bacteria in reverse micelles

    Zhi, Xiaohua; Yang, Haijun; Yuan, Zhuliang; Shen, Jianquan [Beijing National Laboratory for Molecular Sciences (BNLMS), Laboratory of New Materials, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First Street 2, Beijing 100190 (China)


    The micellar formation and entrapment of bacteria cell in reverse micelles were investigated by ultraviolet spectrum (UV), fluorescence spectrum, and scanning electron microscope (SEM). The hydrogen production in reverse micelles was confirmed. The Gompertz equation was employed to evaluate the hydrogen-producing behavior in reverse micellar systems. Different systems including dioctyl sulfosuccinate sodium salt (AOT)-isooctane, sodium dodecyl sulfate (SDS)-benzene and SDS-carbon tetrachloride (CCl{sub 4}) reverse micelles were analysized. The results revealed that the maximum rate of hydrogen production (R{sub m}) was also suitable to formulate the relationship between hydrogen-producing rate and hydrogen productivity in reverse micelles. (author)

  20. Atomistic Simulation of Solubilization of Polycyclic Aromatic Hydrocarbons in a Sodium Dodecyl Sulfate Micelle.

    Liang, Xujun; Marchi, Massimo; Guo, Chuling; Dang, Zhi; Abel, Stéphane


    Solubilization of two polycyclic aromatic hydrocarbons (PAHs), naphthalene (NAP, 2-benzene-ring PAH) and pyrene (PYR, 4-benzene-ring PAH), into a sodium dodecyl sulfate (SDS) micelle was studied through all-atom molecular dynamics (MD) simulations. We find that NAP as well as PYR could move between the micelle shell and core regions, contributing to their distribution in both regions of the micelle at any PAH concentration. Moreover, both NAP and PYR prefer to stay in the micelle shell region, which may arise from the greater volume of the micelle shell, the formation of hydrogen bonds between NAP and water, and the larger molecular volume of PYR. The PAHs are able to form occasional clusters (from dimer to octamer) inside the micelle during the simulation time depending on the PAH concentration in the solubilization systems. Furthermore, the micelle properties (i.e., size, shape, micelle internal structure, alkyl chain conformation and orientation, and micelle internal dynamics) are found to be nearly unaffected by the solubilized PAHs, which is irrespective of the properties and concentrations of PAHs.

  1. Modeling transport and aggregation of volcanic ash particles

    Costa, Antonio; Folch, Arnau; Macedonio, Giovanni; Durant, Adam


    A complete description of ash aggregation processes in volcanic clouds is an very arduous task and the full coupling of ash transport and ash aggregation models is still computationally prohibitive. A large fraction of fine ash injected in the atmosphere during explosive eruptions aggregate because of complex interactions of surface liquid layers, electrostatic forces, and differences in settling velocities. The formation of aggregates of size and density different from those of the primary particles dramatically changes the sedimentation dynamics and results in lower atmospheric residence times of ash particles and in the formation of secondary maxima of tephra deposit. Volcanic ash transport models should include a full aggregation model accounting for all particle class interaction. However this approach would require prohibitive computational times. Here we present a simplified model for wet aggregation that accounts for both atmospheric and volcanic water transport. The aggregation model assumes a fractal relationship for the number of primary particles in aggregates, average efficiencies factors, and collision frequency functions accounting for Brownian motion, laminar and turbulent fluid shear, and differential settling velocity. We implemented the aggregation model in the WRF+FALL3D coupled modelling system and applied it to different eruptions where aggregation has been recognized to play an important role, such as the August and September 1992 Crater Peak eruptions and the 1980 Mt St Helens eruption. Moreover, understanding aggregation processes in volcanic clouds will contribute to mitigate the risks related with volcanic ash transport and sedimentation.

  2. Fractal dimension and mechanism of aggregation of apple juice particles.

    Benítez, E I; Lozano, J E; Genovese, D B


    Turbidity of freshly squeezed apple juice is produced by a polydisperse suspension of particles coming from the cellular tissue. After precipitation of coarse particles by gravity, only fine-colloidal particles remain in suspension. Aggregation of colloidal particles leads to the formation of fractal structures. The fractal dimension is a measure of the internal density of these aggregates and depends on their mechanism of aggregation. Digitized images of primary particles and aggregates of depectinized, diafiltered cloudy apple juice were obtained by scanning electron microscopy (SEM). Average radius of the primary particles was found to be a = 40 ± 11 nm. Maximum radius of the aggregates, R(L), ranged between 250 and 7750 nm. Fractal dimension of the aggregates was determined by analyzing SEM images with the variogram method, obtaining an average value of D(f) = 2.3 ± 0.1. This value is typical of aggregates formed by rapid flocculation or diffusion limited aggregation. Diafiltration process was found to reduce the average size and polydispersity of the aggregates, determined by photon correlation spectroscopy. Average gyration radius of the aggregates before juice diafiltration was found to be R(g) = 629 ± 87 nm. Average number of primary particles per aggregate was calculated to be N = 1174.

  3. Fractals of Silica Aggregates

    ZhinhongLi; DongWu; Yuhansun; JunWang; YiLiu; BaozhongDong; Zhinhong


    Silica aggregates were prepared by base-catalyzed hydrolysis and condensation of alkoxides in alcohol.Polyethylene glycol(PEG) was used as organic modifier.The sols were characterized using Small Angle X-ray Scattering (SAXS) with synchrotron radiation as X-ray source.The structure evolution during the sol-gel process was determined and described in terms of the fractal geometry.As-produced silica aggregates were found to be mass fractals.The fractl dimensions spanned the regime 2.1-2.6 corresponding to more branched and compact structures.Both RLCA and Eden models dominated the kinetic growth under base-catalyzed condition.

  4. Linear, Star, and Comb Oxidation-Responsive Polymers: Effect of Branching Degree and Topology on Aggregation and Responsiveness.

    d'Arcy, Richard; Gennari, Arianna; Donno, Roberto; Tirelli, Nicola


    Families of amphiphilic oxidation-responsive polymers (poly(ethylene glycol)-polysulfides) with different architectures (linear, 4, 6, and 8-armed stars and 10, 15, and 20-armed combs) and compositions (variable ethylene sulfide/propylene sulfide ratio) are prepared. In water, all the polymers assemble in spherical micelles, with critical micellar concentrations <0.01 mg mL(-1) for all the branched polymers. Triple-detection gel permeation chromatography (GPC) and asymmetric field flow fractionation (AFFF) with dynamic and static light scattering detection, respectively, show an increasing compaction of the polymeric coil and a strong reduction of the aggregation number with increasing degree of branching. The key finding of this study is that the kinetics of the oxidative response sharply depend on the branching; in particular, it is highlighted that the degree of branching influences the lag time before a response can be observed rather than the speed of the response itself, a phenomenon that is attributed to a branching-dependent solubility of the oxidant in the polysulfide matrix.

  5. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Cuong, Nguyen-Van [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Department of Chemical Engineering, Ho Chi Minh City University of Industry, 12 Nguyen Van Bao St, Ho Chi Minh (Viet Nam); Jiang, Jian-Lin; Li, Yu-Lun [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China); Chen, Jim-Ray [Department of Pathology, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Jwo, Shyh-Chuan [Division of General Surgery, Chang Gung Memorial Hospital at Keelung, Taiwan and Chang Gung University, College of Medicine, Taoyuan, Taiwan (China); Hsieh, Ming-Fa, E-mail: [Department of Biomedical Engineering, Chung Yuan Christian University, 200, Chung Pei Rd., Chung Li, Taiwan (China)


    The triblock copolymer is composed of two identical hydrophilic segments Monomethoxy poly(ethylene glycol) (mPEG) and one hydrophobic segment poly(ε-caprolactone) (PCL); which is synthesized by coupling of mPEG-PCL-OH and mPEG-COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo) showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded micelles as compared to multiple administrations of free DOX.

  6. Doxorubicin-Loaded PEG-PCL-PEG Micelle Using Xenograft Model of Nude Mice: Effect of Multiple Administration of Micelle on the Suppression of Human Breast Cancer

    Ming-Fa Hsieh


    Full Text Available The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(ethylene glycol (mPEG and one hydrophobic segment poly(ε‑caprolactone (PCL; which is synthesized by coupling of mPEG-PCL-OH and mPEG‑COOH in a mild condition using dicyclohexylcarbodiimide and 4-dimethylamino pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic micelles to accommodate doxorubixin (DOX in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the micelles, have been characterized in our previous study. In this study, DOX was encapsulated into micelles with a drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric micelle (placebo showed a safe dose of PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the tumor growth of human breast cancer cells in nude mice was suppressed by multiple injections (5 mg/kg, three times daily on day 0, 7 and 14 of DOX-loaded micelles as compared to multiple administrations of free DOX.

  7. Lactosylated poly(ethylene oxide)-poly(propylene oxide) block copolymers for potential active targeting: synthesis and physicochemical and self-aggregation characterization

    Cuestas, Maria L.; Glisoni, Romina J. [University of Buenos Aires, Group of Biomaterials and Nanotechnology for Improved Medicines (BIONIMED), Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry (Argentina); Mathet, Veronica L. [National Science Research Council (CONICET) (Argentina); Sosnik, Alejandro, E-mail: [University of Buenos Aires, The Group of Biomaterials and Nanotechnology for Improved Medicines (BIONIMED), Department of Pharmaceutical Technology, Faculty of Pharmacy and Biochemistry (Argentina)


    Aiming to develop polymeric self-assembly nanocarriers with potential applications in active drug targeting to the liver, linear and branched poly(ethylene oxide)-poly(propylene oxide) amphiphiles were conjugated to lactobionic acid (LA), a disaccharide of galactose and gluconic acid, by the conventional Steglich esterification reaction. The conjugation was confirmed by ATR/FT-IR, {sup 1}H-NMR, and {sup 13}C-NMR spectroscopy. Elemental analysis and MALDI-TOF mass spectrometry were employed to elucidate the conjugation extent and the final molecular weight, respectively. The critical micellar concentration (CMC), the size and size distribution and zeta potential of the pristine and modified polymeric micelles under different conditions of pH and temperature were characterized by dynamic light scattering (DLS). Conjugation with LA favored the micellization process, leading to a decrease of the CMC with respect to the pristine counterpart, this phenomenon being independent of the pH and the temperature. At 37 Degree-Sign C, micelles made of pristine copolymers showed a monomodal size distribution between 12.8 and 24.4 nm. Conversely, LA-conjugated micelles showed a bimodal size pattern that comprised a main fraction of relatively small size (11.6-22.2 nm) and a second one with remarkably larger sizes of up to 941.4 nm. The former corresponded to single micelles, while the latter would indicate a secondary aggregation phenomenon. The spherical morphology of LA-micelles was visualized by transmission electron microscopy (TEM). Finally, to assess the ability of the LA-conjugated micelles to interact with lectin-like receptors, samples were incubated with concanavalin A at 37 Degree-Sign C and the size and size distribution were monitored by DLS. Findings indicated that regardless of the relatively weak affinity of this vegetal lectin for galactose, micelles underwent agglutination probably through the interaction of a secondary site in the lectin with the gluconic acid

  8. Geoinformation Generalization by Aggregation

    Tomislav Jogun


    Full Text Available Geoinformation generalization can be divided into model generalization and cartographic generalization. Model generalization is the supervised reduction of data in a model, while cartographic generalization is the reduction of the complexity of map content adapted to the map scale, and/or use by various generalization operators (procedures. The topic of this paper is the aggregation of geoinformation. Generally, aggregation is the joining of nearby, congenial objects, when the distance between them is smaller than the minimum sizes. Most researchers in geoinformation generalization have focused on line features. However, the appearance of web-maps with point features and choropleth maps has led to the development of concepts and algorithms for the generalization of point and polygonal features. This paper considers some previous theoretical premises and actual examples of aggregation for point, line and polygonal features. The algorithms for aggregation implemented in commercial and free GIS software were tested. In the conclusion, unresolved challenges that occur in dynamic cartographic visualizations and cases of unusual geometrical features are highlighted.

  9. Erosion of dust aggregates

    Seizinger, Alexander; Kley, Wilhelm


    Aims: The aim of this work is to gain a deeper insight into how much different aggregate types are affected by erosion. Especially, it is important to study the influence of the velocity of the impacting projectiles. We also want to provide models for dust growth in protoplanetary disks with simple recipes to account for erosion effects. Methods: To study the erosion of dust aggregates we employed a molecular dynamics approach that features a detailed micro-physical model of the interaction of spherical grains. For the first time, the model has been extended by introducing a new visco-elastic damping force which requires a proper calibration. Afterwards, different sample generation methods were used to cover a wide range of aggregate types. Results: The visco-elastic damping force introduced in this work turns out to be crucial to reproduce results obtained from laboratory experiments. After proper calibration, we find that erosion occurs for impact velocities of 5 m/s and above. Though fractal aggregates as ...

  10. Diffusion in aggregated soil.

    Rappoldt, C.


    The structure of an aggregated soil is characterized by the distribution of the distance from an arbitrary point in the soil to the nearest macropore or crack. From this distribution an equivalent model system is derived to which a diffusion model can be more easily applied. The model system consist

  11. Studies on the photophysical properties of 1,8-naphthalimide derivative and aggregation induced emission recognition for casein

    Sun, Yang, E-mail: [Department of Chemistry and Chemical Engineering, Xi' an University of Arts and Science, No. 168, Taibai South Road, Xi' an, Shaanxi 710065 (China); Liang, Xuhua; Fan, Jun [School of Chemical Engineering, Northwest University, No. 229, Taibai North Road, Xi' an, Shaanxi 710069 (China); Han, Quan, E-mail: [Department of Chemistry and Chemical Engineering, Xi' an University of Arts and Science, No. 168, Taibai South Road, Xi' an, Shaanxi 710065 (China)


    A novel water-soluble 1,8-naphthalimide derivative 1, bearing two acetic carboxylic groups, exhibited fluorescent turn-on recognition for casein micelle based on the aggregation induced emission (AIE) character. The photophysical properties of 1 consisting of donor and acceptor units were investigated by the solvation effect. Changing from polar to non-polar solvent increased the solvent interaction; both the excitation and emission spectra were shifted to shorter wavelength and intensity decreased through taking advantage of twisted intramolecular charge transfer (TICT) and self-association fluorescence emission. Moreover, the red-shift and quenching in protic solvent were caused by the excited-state hydrogen bond strengthening effect. The density functional theory (DFT) and time dependent density functional theory (TDDFT) were used to obtain the most stable structure, electronic excitation energy, dipole moments and charge distribution. The AIE mechanism of 1 with casein micelle was due to 1 docked in the hydrophobic cavity between sub-micelles and bound with amino acid residues, resulting in the aggregation of 1 on the casein micelle surface and emission enhancement, based on which, a novel casein assay method was developed. The proposed method exhibited a good linear range from 0.1 to 10.5 μg mL{sup −1}, with the detection limit of 3.0 ng mL{sup −1}. Satisfactory reproducibility, reversibility and a short response time were realized. This method was applied for the determination of casein in milk powder samples, avoiding the interferences from other components and illegal additives in milk. -- Highlights: • A water-soluble 1,8-naphthalimide-based fluorescent probe 1 was synthesized. • Photophysical characterization of 1 was studied. • Aggregation induced emission enhancement of 1 with casein was investigated. • A novel casein quantification method was developed.

  12. Urea decreases specific ion effects on the LCST of PMMA-block-PDMAEMA aggregates

    João Carlos Perbone de Souza


    Full Text Available Urea is a well-known additive used as a mild protein denaturant. The effect of urea on proteins, micellar systems and other colloids is still under debate. In particular, urea has shown interesting effects on the ion binding in systems like charged micelles, vesicles or Langmuir-Blodgett films. The urea effect on polymeric aggregates in water is still an open field. For instance, the additive may affect properties such as cmc, LCST, UCST and others. In particular, LCST is a property that can be very convenient for designing smart systems that respond to temperature. Previous studies have indicated that the LCST of positive charged copolymers aggregates based on poly[N-dimethyl(ethylamine methacrylate], PDMAEMA, can be nicely modulated by anions in aqueous solution and such phenomenon depends on the nature of the anion present. In this work, it has been demonstrated that urea also affects the LCST of PMMA-block-PDMAEMA aggregates in aqueous solution. In addition, in the presence of high concentrations of the additive, the specific behavior of the anions is lost, supporting the general mechanism of urea reducing the differences on ion binding to surfaces in aqueous solutions. To the best of our knowledge, this is the first time those phenomena are shown in polymer micelles.

  13. The capture and stabilization of curcumin using hydrophobically modified polyacrylate aggregates and hydrogels.

    Harada, Takaaki; Pham, Duc-Truc; Lincoln, Stephen F; Kee, Tak W


    Hydrophobically modified polyacrylates are shown to suppress the degradation of the medicinal pigment curcumin under physiological conditions. In aqueous solution, the 3% octadecyl randomly substituted polyacrylate, PAAC18, forms micelle-like aggregates at a concentration of 1 wt %. Under both conditions, PAAC18 shows a remarkable ability to suppress the degradation of curcumin at pH 7.4 and 37 °C such that its degradation half-life is increased by 1600-2000-fold. The suppression of degradation is attributed to hydrophobic interactions between curcumin and the octadecyl substituents of PAAC18 within the micelle-like aggregates and the hydrogel, as indicated by 2D NOESY (1)H NMR spectroscopy. UV-visible absorption titration results are consistent with the interaction of curcumin with five octadecyl substituents on average, which appears to substantially exclude water and greatly decrease the curcumin degradation rate. Dynamic light scattering and zeta potential measurements show the average hydrodynamic diameters of the PAAC18 aggregates to be 0.86-1.15 μm with a negative surface charge. In contrast to the octadecyl substitution, the 3% dodecyl randomly substituted polyacrylate, PAAC12, shows a negligible effect on slowing the degradation of curcumin, consistent with the dodecyl substituents being insufficiently long to capture curcumin in a adequately hydrophobic environment. These observations indicate the potential for PAAC18 to act as a model drug delivery system.

  14. Micellar aggregates of saponins from Chenopodium quinoa: characterization by dynamic light scattering and transmission electron microscopy.

    Verza, S G; de Resende, P E; Kaiser, S; Quirici, L; Teixeira, H F; Gosmann, G; Ferreira, F; Ortega, G G


    Entire seeds of Chenopodium quinoa Willd are a rich protein source and are also well-known for their high saponin content. Due to their amphiphily quinoa saponins are able to form intricate micellar aggregates in aqueous media. In this paper we study the aggregates formed by self-association of these compounds from two quinoa saponin fractions (FQ70 and FQ90) as well as several distinctive nanostructures obtained after their complexation with different ratios of cholesterol (CHOL) and phosphatidylcholine (PC). The FQ70 and FQ90 fractions were obtained by reversed-phase preparative chromatography. The structural features of their resulting aggregates were determined by Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). Novel nanosized spherical vesicles formed by self-association with mean diameter about 100-200 nm were observed in FQ70 aqueous solutions whereas worm-like micelles an approximate width of 20 nm were detected in FQ90 aqueous solutions. Under experimental conditions similar to those reported for the preparation of Quillaja saponaria ISCOM matrices, tubular and ring-like micelles arose from FQ70:CHOL:PC and FQ90:CHOL:PC formulations, respectively. However, under these conditions no cage-like ISCOM matrices were observed. The saponin composition of FQ70 and FQ90 seems to determine the nanosized structures viewed by TEM. Phytolaccagenic acid, predominant in FQ70 and FQ90 fractions, is accountable for the formation of the nanosized vesicles and tubular structures observed by TEM in the aqueous solutions of both samples. Conversely, ring-like micelles observed in FQ90:CHOL:PC complexes can be attributed to the presence of less polar saponins present in FQ90, in particular those derived from oleanolic acid.

  15. Effect of polyoxypropylene chain length on the critical micelle concentration of propylene oxide-ethylene oxide block copolymers

    ZHANG Zhi-guo; YIN Hong


    In this work, the surface activity of block copolymer nonionic surfactants (RPE) has been determined, i.e., critical micelle concentration (CMC), surface excess concentration (Γ), surface area demand per molecule (A), surface tension at CMC (yCMC). A linear decrease of ln[CMC] vs number of oxypropylene units in copolymer molecule was observed. The change in the work of cohesion per oxypropylene group when passing from molecular into micellar state, calculated from the Shinoda equation, was 0.43kT for the studied compounds.

  16. Block copolymer micelles as nanocontainers for controlled release of proteins from biocompatible oil phases.

    Miller, Andrew C; Bershteyn, Anna; Tan, Wuisiew; Hammond, Paula T; Cohen, Robert E; Irvine, Darrell J


    Biocompatible oils are used in a variety of medical applications ranging from vaccine adjuvants to vehicles for oral drug delivery. To enable such nonpolar organic phases to serve as reservoirs for delivery of hydrophilic compounds, we explored the ability of block copolymer micelles in organic solvents to sequester proteins for sustained release across an oil-water interface. Self-assembly of the block copolymer, poly(-caprolactone)-block-poly(2-vinyl pyridine) (PCL-b-P2VP), was investigated in toluene and oleic acid, a biocompatible naturally occurring fatty acid. Micelle formation in toluene was characterized by dynamic light scattering (DLS) and atomic force microscopy (AFM) imaging of micelles cast onto silicon substrates. Cryogenic transmission electron microscopy confirmed a spherical morphology in oleic acid. Studies of homopolymer solubility implied that micelles in oleic acid consist of a P2VP corona and a PCL core, while P2VP formed the core of micelles assembled in toluene. The loading of two model proteins (ovalbumin (ova) and bovine serum albumin (BSA)) into micelles was demonstrated with loadings as high as 7.8% wt of protein per wt of P2VP in oleic acid. Characterization of block copolymer morphology in the two solvents after protein loading revealed spherical particles with similar size distributions to the as-assembled micelles. Release of ova from micelles in oleic acid was sustained for 12-30 h upon placing the oil phase in contact with an aqueous bath. Unique to the situation of micelle assembly in an oily phase, the data suggest protein is sequestered in the P2VP corona block of PCL-b-P2VP micelles in oleic acid. More conventionally, protein loading occurs in the P2VP core of micelles assembled in toluene.

  17. Fault tolerant aggregation for power system services

    Kosek, Anna Magdalena; Gehrke, Oliver; Kullmann, Daniel


    Exploiting the flexibility in distributed energy resources (DER) is seen as an important contribution to allow high penetrations of renewable generation in electrical power systems. However, the present control infrastructure in power systems is not well suited for the integration of a very large...... number of small units. A common approach is to aggregate a portfolio of such units together and expose them to the power system as a single large virtual unit. In order to realize the vision of a Smart Grid, concepts for flexible, resilient and reliable aggregation infrastructures are required...

  18. Sequence dependent aggregation of peptides and fibril formation

    Hung, Nguyen Ba; Le, Duy-Manh; Hoang, Trinh X.


    Deciphering the links between amino acid sequence and amyloid fibril formation is key for understanding protein misfolding diseases. Here we use Monte Carlo simulations to study the aggregation of short peptides in a coarse-grained model with hydrophobic-polar (HP) amino acid sequences and correlated side chain orientations for hydrophobic contacts. A significant heterogeneity is observed in the aggregate structures and in the thermodynamics of aggregation for systems of different HP sequences and different numbers of peptides. Fibril-like ordered aggregates are found for several sequences that contain the common HPH pattern, while other sequences may form helix bundles or disordered aggregates. A wide variation of the aggregation transition temperatures among sequences, even among those of the same hydrophobic fraction, indicates that not all sequences undergo aggregation at a presumable physiological temperature. The transition is found to be the most cooperative for sequences forming fibril-like structures. For a fibril-prone sequence, it is shown that fibril formation follows the nucleation and growth mechanism. Interestingly, a binary mixture of peptides of an aggregation-prone and a non-aggregation-prone sequence shows the association and conversion of the latter to the fibrillar structure. Our study highlights the role of a sequence in selecting fibril-like aggregates and also the impact of a structural template on fibril formation by peptides of unrelated sequences.

  19. Pyridine Aggregation in Helium Nanodroplets

    Nieto, Pablo; Poerschke, Torsten; Habig, Daniel; Schwaab, Gerhard; Havenith, Martina


    Pyridine crystals show the unusual property of isotopic polymorphism. Experimentally it has been observed that deuterated pyridine crystals exist in two phases while non-deuterated pyridine does not show a phase transition. Therefore, although isotopic substitution is the smallest possible modification of a molecule it greatly affects the stability of pyridine crystals. A possible experimental approach in order to understand this striking effect might be the study of pyridine aggregation for small clusters. By embedding the clusters in helium nanodroplets the aggregates can be stabilized and studied by means of Infrared Depletion Spectroscopy. Pyridine oligomers were investigated in the C-H asymmetric vibration region (2980-3100 cm-1) using this experimental technique. The number of molecules for the clusters responsibles for each band were determined by means of pick-up curves as well as mass sensitive depletion spectra. Furthermore, the intensity dependence of the different bands on applying a dc electric field was studied. The assignment of the different structures for pyridine clusters on the basis of these measurements were also carried out. S. Crawford et al., Angew. Chem. Int. Ed., 48, 755 (2009).

  20. SDS胶束体系中亚甲蓝与血清白蛋白的相互作用%The Interaction of Methylene Blue and Bovine Serum Albumin in SDS Micelle System

    郭荣; 范国康; 刘天晴; 焦新安


    The interaction of methylene blue(MB) and bovine serum albumin(BSA) is investigated in the SDS micelle system which is simulated as one kind of coexisted albumin. The interaction parameters of MB and BSA and simulated albumin such as partition coefficient κ 、 normal binding free energy Δ G 、 average binding number n are calculated. The results show that most of MB is in the form of monomer in SDS micelle systems; the main interaction of MB and BSA is of static electric and H-bind force,and that of MB and simulated albumin is only of static electric force.

  1. Simulation of red blood cell aggregation in shear flow.

    Lim, B; Bascom, P A; Cobbold, R S


    A simulation model has been developed for red blood cell (RBC) aggregation in shear flow. It is based on a description of the collision rates of RBC, the probability of particles sticking together, and the breakage of aggregates by shear forces. The influence of shear rate, hematocrit, aggregate fractal dimension, and binding strength on aggregation kinetics were investigated and compared to other theoretical and experimental results. The model was used to simulate blood flow in a long large diameter tube under steady flow conditions at low Reynolds numbers. The time and spatial distribution of the state of aggregation are shown to be in qualitative agreement with previous B-mode ultrasound studies in which a central region of low echogenicity was noted. It is suggested that the model can provide a basis for interpreting prior measurements of ultrasound echogenicity and may help relate them to the local state of aggregation.

  2. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

    Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang


    Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

  3. Pharmacokinetics and biodistribution of polymeric micelles of paclitaxel with Pluronic P123

    Li-mei HAN; Lie GUO; Li-jun ZHANG; Qing-song WANG; Xiao-ling FANG


    Aim: To investigate the preparation, in vitro release, in vivo pharmacokinetics and tissue distribution of a novel polymeric micellar formulation of paclitaxel (PTX) with Pluronic P123. Methods: The polymeric micelles of paclitaxel with Pluronic PI23 were prepared by a solid dispersion method. The characteristics of micelles including particle size distribution, morphology and in vitro release of PTX from micelles were carried out. PTX-loaded micellar solutions were administered through the tail vein to healthy Sprague-Dawley rats and Kunming strain mice to assess the pharmacokinetics and tissue distribution of PTX, respectively. Taxol, the commercially available intravenous formulation of PTX, was also administered as control. Results: By using a dynamic light scattering sizer and a transmission electron microscopy, it was shown that the PTX-loaded micelles had a mean size of approximately 25 nm with narrow size distribution and a spherical shape. PTX was continuously released from Pluronic PI23 micelles in release medium containing 1 mol/L sodium salicylate for 24 h at 37℃. In the pharmacokinetic assessment, t1/2β and AUC of micelle formulation were 2.3 and 2.9-fold higher than that of Taxol injection. And the PTX-loaded micelles increased the uptake of PTX in the plasma, ovary and uterus, lung, and kidney, but decreased uptake in the liver and brain in the biodistribution study. Conclusion: Polymeric micelles using Pluronic P123 can effectively solubilize PTX, prolong blood circulation time and modify the biodistribution of PTX.

  4. Peptide-conjugated micelles as a targeting nanocarrier for gene delivery

    Lin, Wen Jen, E-mail:; Chien, Wei Hsuan [National Taiwan University, School of Pharmacy, Graduate Institute of Pharmaceutical Sciences (China)


    The aim of this study was to develop peptide-conjugated micelles possessing epidermal growth factor receptor (EGFR) targeting ability for gene delivery. A sequence-modified dodecylpeptide, GE11(2R), with enhancing EGF receptor binding affinity, was applied in this study as a targeting ligand. The active targeting micelles were composed of poly(d,l-lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) copolymer conjugated with GE11(2R)-peptide. The particle sizes of peptide-free and peptide-conjugated micelles were 277.0 ± 5.1 and 308.7 ± 14.5 nm, respectively. The peptide-conjugated micelles demonstrated the cellular uptake significantly higher than peptide-free micelles in EGFR high-expressed MDA-MB-231 and MDA-MB-468 cells due to GE11(2R)-peptide specificity. Furthermore, the peptide-conjugated micelles were able to encapsulate plasmid DNA and expressed cellular transfection higher than peptide-free micelles in EGFR high-expressed cells. The EGFR-targeting delivery micelles enhanced DNA internalized into cells and achieved higher cellular transfection in EGFR high-expressed cells.

  5. Tuneable & degradable polymeric micelles for drug delivery: from synthesis to feasibility in vivo

    Rijcken, C.J.F.


    In recent years, colloidal systems (e.g. liposomes, nanoparticles and micelles) are increasingly applied as vehicles for controlled drug delivery purposes. Ideally, the encapsulation of hydrophobic drugs in a micellar core prolongs the systemic circulation and drug-loaded micelles selectively accumu

  6. Effect of Spacers on CMCs and Micelle-forming Enthalpies of Gemini Surfactants by Titration Microcalorimetry


    The critical micelle concentrations (CMC) and the micelle-forming enthalpies (D Hmic) of gemini surfactants were first measured by the precise titration microcalorimetry. The results showed that D Hmic values are negative, and there is an exothermal minimum between s=4 and s=6. Furthermore, the CMCs of the surfactants are in good agreement with literature values.

  7. Comprehensive theory for star-like polymer micelles: combining classical nucleation and polymer brush theory

    Sprakel, J.H.B.; Leermakers, F.A.M.; Cohen Stuart, M.A.; Besseling, N.A.M.


    A comprehensive theory is proposed that combines classical nucleation and polymer brush theory to describe star-like polymer micelles. With a minimum of adjustable parameters, the model predicts properties such as critical micelle concentrations and micellar size distributions. The validity of the p

  8. Histological study on side effects and tumor targeting of a block copolymer micelle on rats.

    Kawaguchi, Takanori; Honda, Takashi; Nishihara, Masamichi; Yamamoto, Tatsuhiro; Yokoyama, Masayuki


    Histological examinations were performed with polymeric micelle-injected rats for evaluations of possible toxicities of polymeric micelle carriers. Weight of major organs as well as body weight of rats was measured after multiple intravenous injections of polymeric micelles forming from poly(ethylene glycol)-b-poly(aspartate) block copolymer. No pathological toxic side effects were observed at two different doses, followed only by activation of the mononuclear phagocyte system (MPS) in the spleen, liver, lung, bone marrow, and lymph node. This finding confirms the absence of--or the very low level of--in vivo toxicity of the polymeric micelle carriers that were reported in previous animal experiments and clinical results. Then, immunohistochemical analyses with a biotinylated polymeric micelle confirmed specific accumulation of the micelle in the MPS. The immunohistochemical analyses also revealed, first, very rapid and specific accumulation of the micelle in the vasculatures of tumor capsule of rat ascites hepatoma AH109A, and second, the micelle's scanty infiltration into tumor parenchyma. This finding suggests a unique tumor-accumulation mechanism that is very different from simple EPR effect-based tumor targeting.

  9. Design of block-copolymer-based micelles for active and passive targeting

    Lebouille, Jérôme G.J.L.; Leermakers, Frans A.M.; Cohen Stuart, Martien A.; Tuinier, Remco


    A self-consistent field study is presented on the design of active and passive targeting block-copolymeric micelles. These micelles form in water by self-assembly of triblock copolymers with a hydrophilic middle block and two hydrophobic outer blocks. A minority amount of diblock copolymers with the

  10. Green synthetic, multifunctional hybrid micelles with shell embedded magnetic nanoparticles for theranostic applications.

    Li, Yongyong; Ma, Junping; Zhu, Haiyan; Gao, Xiaolong; Dong, Haiqing; Shi, Donglu


    The objective of this study is to design and develop a green-synthetic, multifunctional hybrid micelles with shell embedded magnetic nanoparticles for theranostic applications. The hybrid micelles were engineered based on complex micelles self-assembled from amphiphilic block copolymers Pluronic F127 and peptide-amphiphile (PA) pal-AAAAHHHD. The reason to choose PA is due to its amphiphilic character and the coordination capability for Fe(3+) and Fe(2+). The PA incorporation allows the in situ growth of the magnetic iron oxide nanoparticles onto the complex micelles, to yield the nanostructures with shell embedded magnetic nanoparticles at an ambient condition without any organic solvents. The anticancer drug doxorubicin (DOX) can be efficiently loaded into the hybrid micelles. Interestingly, the magnetic nanoparticles anchored on the shell were found to significantly retard the DOX release behavior of the drug loaded hybrid micelles. It was proposed that a cross-linking effect of the shell by magnetic nanoparticles is a key to underlie the above intriguing phenomenon, which could enhance the stability and control the drug diffusion of the hybrid micelles. Importantly, in vitro and in vivo magnetic resonance imaging (MRI) revealed the potential of these hybrid micelles to be served as a T2-weighted MR imaging contrast enhancer for clinical diagnosis.

  11. Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

    Li Xinru


    Full Text Available Abstract Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol-poly(lactide (mPEG-PLA and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15, were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12. Stability analysis of the mixed micelles in bovine serum albumin (BSA solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.

  12. The association of low-molecular-weight hydrophobic compounds with native casein micelles in bovine milk.

    Cheema, M; Mohan, M S; Campagna, S R; Jurat-Fuentes, J L; Harte, F M


    The agreed biological function of the casein micelles in milk is to carry minerals (calcium, magnesium, and phosphorus) from mother to young along with amino acids for growth and development. Recently, native and modified casein micelles were used as encapsulating and delivery agents for various hydrophobic low-molecular-weight probes. The ability of modified casein micelles to bind certain probes may derive from the binding affinity of native casein micelles. Hence, a study with milk from single cows was conducted to further elucidate the association of hydrophobic molecules into native casein micelles and further understand their biological function. Hydrophobic and hydrophilic extraction followed by ultraperformance liquid chromatography-high resolution mass spectrometry analysis were performed over protein fractions obtained from size exclusion fractionation of raw skim milk. Hydrophobic compounds, including phosphatidylcholine, lyso-phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin, showed strong association exclusively to casein micelles as compared with whey proteins, whereas hydrophilic compounds did not display any preference for their association among milk proteins. Further analysis using liquid chromatography-tandem mass spectrometry detected 42 compounds associated solely with the casein-micelles fraction. Mass fragments in tandem mass spectrometry identified 4 of these compounds as phosphatidylcholine with fatty acid composition of 16:0/18:1, 14:0/16:0, 16:0/16:0, and 18:1/18:0. These results support that transporting low-molecular-weight hydrophobic molecules is also a biological function of the casein micelles in milk.

  13. The Role of Decorated SDS Micelles in Sub-CMC Protein Denaturation and Association

    Andersen, Kell; Oliveira, Cristiano Luis Pinto De; Larsen, K.L.;


    . Our data provide key structural insights into decorated micelle complexes with proteins, revealing a remarkable diversity in the different conformations they can stabilize. The data highlight that a minimum decorated micelle size, which may be a key driving force for intermolecular protein association...

  14. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    Gou, MaLing; Shi, HuaShan; Guo, Gang; Men, Ke; Zhang, Juan; Zheng, Lan; Li, ZhiYong; Luo, Feng; Qian, ZhiYong; Zhao, Xia; Wei, YuQuan


    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ɛ-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ~ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  15. Molecular dynamics simulations of helical antimicrobial peptides in SDS micelles: what do point mutations achieve?

    Khandelia, Himanshu; Kaznessis, Yiannis N


    We report long time scale simulations of the 18-residue helical antimicrobial peptide ovispirin-1 and its analogs novispirin-G10 and novispirin-T7 in SDS micelles. The SDS micelle serves as an economical and effective model for a cellular membrane. Ovispirin, which is initially placed along a mic...

  16. Separation of racemic mixture by ultrafiltration of enantioselective micelles. 2 (De) complexation kinetics

    Overdevest, P.E.M.; Schutyser, M.A.I.; Bruin, de T.J.M.; Riet, van 't K.; Keurentjes, J.T.F.; Padt, van der A.


    The application of enantioselective micelles in ultrafiltration systems can be an alternative route to meet the increasing demand for enantiopure products. We have studied the separation of D,L-phenylalanine (Phe) by cholesteryl-L-glutamate:CuII (CLG:CuII) anchored in nonionic micelles (intrinsic en

  17. Deoxycholic acid-grafted PEGylated chitosan micelles for the delivery of mitomycin C.

    Zhang, Xiu-Rong; Shi, Nian-Qiu; Zhao, Yang; Zhu, He-Yun; Guan, Jiao; Jin, Ying


    Mitomycin C (MTC) was incorporated to a micelle system preparing from a polymer named deoxycholic acid chitosan-grafted poly(ethylene glycol) methyl ether (mPEG-CS-DA). mPEG-CS-DA was synthesized and characterized by (1)H nuclear magnetic resonance ((1)H-NMR) and Fourier transform infrared spectroscopy. mPEG-CS-DA formed a core-shell micellar structure with a critical micelle concentration of 6.57 µg/mL. The mPEG-CS-DA micelles were spherical with a hydrodynamic diameter of about 231 nm. After poly(ethylene glycol)ylation of deoxycholic acid chitosan (CS-DA), the encapsulation efficiency and drug loading efficiency increased from 50.62% to 56.42% and from 20.51% to 24.13%, respectively. The mPEG-CS-DA micelles possessed a higher drug release rate than the CS-DA micelles. For pharmacokinetics, the area under the curve (AUC) of the mPEG-CS-DA micelles was 1.5 times higher than that of MTC injection, and these micelles can enhance the bioavailability of MTC. mPEG-CS-DA micelles reduced the distribution of MTC in almost all normal tissues and had the potential to improve the kidney toxicity caused by MTC injection.

  18. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Zheng Lan; Zhao Xia, E-mail: [West China Second University Hospital, West China Women' s and Children' s Hospital, Sichuan University, Chengdu 610041 (China)


    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly({epsilon}-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and {approx} 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  19. Delivery of the photosensitizer Pc 4 in PEG-PCL micelles for in vitro PDT studies.

    Master, Alyssa M; Rodriguez, Myriam E; Kenney, Malcolm E; Oleinick, Nancy L; Gupta, Anirban Sen


    The silicon phthalocyanine Pc 4 is a second-generation photosensitizer that has several properties superior to other photosensitizers currently approved by the FDA, and it has shown significant promise for photodynamic therapy (PDT) in several cancer cells in vitro and model tumor systems in vivo. However, because of the high hydrophobicity of Pc 4, its formulation for in vivo delivery and favorable biodistribution become challenging. To this end, we are studying encapsulation and delivery of Pc 4 in block copolymer micelles. Here, we report the development of biocompatible PEG-PCL micelle nanoparticles, encapsulation of Pc 4 within the micelle core by hydrophobic association with the PCL block, and in vitro PDT studies of the micelle-formulated Pc 4 in MCF-7c3 human breast cancer cells. Our studies demonstrate efficient encapsulation of Pc 4 in the micelles, intracellular uptake of the micelle-formulated Pc 4 in cells, and significant cytotoxic effect of the formulation upon photoirradiation. Quantitative estimation of the extent of Pc 4 loading in the micelles and the photocytotoxicity of the micelle-incorporated Pc 4 demonstrate the promise of our approach to develop a biocompatible nanomedicine platform for tumor-targeted delivery of Pc 4 for site-selective PDT.

  20. Self-consistent-field calculations of proteinlike incorporations in polyelectrolyte complex micelles

    Lindhoud, S.; Cohen Stuart, M.A.; Norde, W.; Leermakers, F.A.M.


    Self-consistent field theory is applied to model the structure and stability of polyelectrolyte complex micelles with incorporated protein (molten globule) molecules in the core. The electrostatic interactions that drive the micelle formation are mimicked by nearest-neighbor interactions using

  1. Modeling the Interaction of Dodecylphosphocholine Micelles with the Anticoccidial Peptide PW2 Guided by NMR Data

    Francisco Gomes-Neto


    Full Text Available Antimicrobial peptides are highly dynamic entities that acquire structure upon binding to a membrane interface. To better understand the structure and the mechanism for the molecular recognition of dodecylphosphocholine (DPC micelles by the anticoccidial peptide PW2, we performed molecular dynamics (MD simulations guided by NMR experimental data, focusing on strategies to explore the transient nature of micelles, which rearrange on a millisecond to second timescale. We simulated the association of PW2 with a pre-built DPC micelle and with free-DPC molecules that spontaneously forms micelles in the presence of the peptide along the simulation. The simulation with spontaneous micelle formation provided the adequate environment which replicated the experimental data. The unrestrained MD simulations reproduced the NMR structure for the entire 100 ns MD simulation time. Hidden discrete conformational states could be described. Coulomb interactions are important for initial approximation and hydrogen bonds for anchoring the aromatic region at the interface, being essential for the stabilization of the interaction. Arg9 is strongly attached with phosphate. We observed a helix elongation process stabilized by the intermolecular peptide-micelle association. Full association that mimics the experimental data only happens after complete micelle re-association. Fast micelle dynamics without dissociation of surfactants leads to only superficial binding.

  2. Shaping and patterning gold nanoparticles via micelle templated photochemistry

    Kundrat, F.; Baffou, G.; Polleux, J.


    Shaping and positioning noble metal nanostructures are essential processes that still require laborious and sophisticated techniques to fabricate functional plasmonic interfaces. The present study reports a simple photochemical approach compatible with micellar nanolithography and photolithography that enables the growth, arrangement and shaping of gold nanoparticles with tuneable plasmonic resonances on glass substrates. Ultraviolet illumination of surfaces coated with gold-loaded micelles leads to the formation of gold nanoparticles with micro/nanometric spatial resolution without requiring any photosensitizers or photoresists. Depending on the extra-micellar chemical environment and the illumination wavelength, block copolymer micelles act as reactive and light-responsive templates, which enable to grow gold deformed nanoparticles (potatoids) and nanorings. Optical characterization reveals that arrays of individual potatoids and rings feature a localized plasmon resonance around 600 and 800 nm, respectively, enhanced photothermal properties and high temperature sustainability, making them ideal platforms for future developments in nanochemistry and biomolecular manipulation controlled by near-infrared-induced heat.Shaping and positioning noble metal nanostructures are essential processes that still require laborious and sophisticated techniques to fabricate functional plasmonic interfaces. The present study reports a simple photochemical approach compatible with micellar nanolithography and photolithography that enables the growth, arrangement and shaping of gold nanoparticles with tuneable plasmonic resonances on glass substrates. Ultraviolet illumination of surfaces coated with gold-loaded micelles leads to the formation of gold nanoparticles with micro/nanometric spatial resolution without requiring any photosensitizers or photoresists. Depending on the extra-micellar chemical environment and the illumination wavelength, block copolymer micelles act as

  3. Mechano-responsive hydrogels crosslinked by reactive block copolymer micelles

    Xiao, Longxi

    Hydrogels are crosslinked polymeric networks that can swell in water without dissolution. Owing to their structural similarity to the native extracelluar matrices, hydrogels have been widely used in biomedical applications. Synthetic hydrogels have been designed to respond to various stimuli, but mechanical signals have not incorporated into hydrogel matrices. Because most tissues in the body are subjected to various types of mechanical forces, and cells within these tissues have sophisticated mechano-transduction machinery, this thesis is focused on developing hydrogel materials with built-in mechano-sensing mechanisms for use as tissue engineering scaffolds or drug release devices. Self-assembled block copolymer micelles (BCMs) with reactive handles were employed as the nanoscopic crosslinkers for the construction of covalently crosslinked networks. BCMs were assembled from amphiphilic diblock copolymers of poly(n-butyl acrylate) and poly(acrylic acid) partially modified with acrylate. Radical polymerization of acrylamide in the presence of micellar crosslinkers gave rise to elastomeric hydrogels whose mechanical properties can be tuned by varying the BCM composition and concentration. TEM imaging revealed that the covalently integrated BCMs underwent strain-dependent reversible deformation. A model hydrophobic drug, pyrene, loaded into the core of BCMs prior to the hydrogel formation, was dynamically released in response to externally applied mechanical forces, through force-induced reversible micelle deformation and the penetration of water molecules into the micelle core. The mechano-responsive hydrogel has been studied for tissue repair and regeneration purposes. Glycidyl methacrylate (GMA)-modified hyaluronic acid (HA) was photochemically crosslinked in the presence of dexamethasone (DEX)-loaded crosslinkable BCMs. The resultant HA gels (HAxBCM) contain covalently integrated micellar compartments with DEX being sequestered in the hydrophobic core. Compared

  4. Factors influencing casein micelle size in milk of individual cows: Genetic variants and glycosylation of k-casein

    Bijl, E.; Vries, de R.F.M.; Valenberg, van H.J.F.; Huppertz, T.; Hooijdonk, van A.C.M.


    The average casein micelle size varies widely between milk samples of individual cows. The factors that cause this variation in size are not known but could provide more insight into casein micelle structure and into the physiology of casein micelle formation. The objective of this research was ther

  5. Aggregation of organic matter by pelagic tunicates

    Pomeroy, L.R. (Univ. of Georgia, Athens); Deibel, D.


    Three genera of pelagic tunicates were fed concentrates of natural seston and an axenic diatom culture. Fresh and up to 4-day-old feces resemble flocculent organic aggregates containing populations of microorganisms, as described from highly productive parts of the ocean, and older feces resemble the nearly sterile flocculent aggregates which are ubiquitous in surface waters. Fresh feces consist of partially digested phytoplankton and other inclusions in an amorphous gelatinous matrix. After 18 to 36 h, a population of large bacteria develops in the matrix and in some of the remains of phytoplankton contained in the feces. From 48 to 96 h, protozoan populations arise which consume the bacteria and sometimes the remains of the phytoplankton in the feces. Thereafter only a sparse population of microorganisms remains, and the particles begin to fragment. Water samples taken in or below dense populations of salps and doliolids contained greater numbers of flocculent aggregates than did samples from adjacent stations.

  6. Factors affecting the stability of drug-loaded polymeric micelles and strategies for improvement

    Zhou, Weisai; Li, Caibin; Wang, Zhiyu; Zhang, Wenli; Liu, Jianping


    Polymeric micelles (PMs) self-assembled by amphiphilic block copolymers have been used as promising nanocarriers for tumor-targeted delivery due to their favorable properties, such as excellent biocompatibility, prolonged circulation time, favorable particle sizes (10-100 nm) to utilize enhanced permeability and retention effect and the possibility for functionalization. However, PMs can be easily destroyed due to dilution of body fluid and the absorption of proteins in system circulation, which may induce drug leakage from these micelles before reaching the target sites and compromise the therapeutic effect. This paper reviewed the factors that influence stability of micelles in terms of thermodynamics and kinetics consist of the critical micelle concentration of block copolymers, glass transition temperature of hydrophobic segments and polymer-polymer and polymer-cargo interaction. In addition, some effective strategies to improve the stability of micelles were also summarized.

  7. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles

    Shi, Yunzhou; Kim, Sungwon; Huff, Terry B.; Borgens, Richard B.; Park, Kinam; Shi, Riyi; Cheng, Ji-Xin


    Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(D,L-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.

  8. The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles.

    van Hasselt, P M; Janssens, G E P J; Slot, T K; van der Ham, M; Minderhoud, T C; Talelli, M; Akkermans, L M; Rijcken, C J F; van Nostrum, C F


    The purpose of this study was to assess the ability of polymeric micelles to enable gastrointestinal absorption of the extremely hydrophobic compound vitamin K, by comparison of its absorption in bile duct ligated and sham operated rats. Hereto, vitamin K was encapsulated in micelles composed of mPEG(5000)-b-p(HPMAm-lac(2)), a thermosensitive block copolymer. Vitamin K plasma levels rose significantly upon gastric administration of 1 mg vitamin K encapsulated in polymeric micelles in sham operated rats, but not after bile duct ligation (AUC 4543 and 1.64 ng/mL/h respectively, pvitamin K from polymeric micelles is mediated by free bile and that uptake of intact micelles through pinocytosis is insignificant.

  9. Tumor homing indocyanine green encapsulated micelles for near infrared and photoacoustic imaging of tumors.

    Uthaman, Saji; Bom, Joon-suk; Kim, Hyeon Sik; John, Johnson V; Bom, Hee-Seung; Kim, Seon-Jong; Min, Jung-Joon; Kim, Il; Park, In-Kyu


    Photoacoustic imaging (PAI) is an emerging analytical modality that is under intense preclinical development for the early diagnosis of various medical conditions, including cancer. However, the lack of specific tumor targeting by various contrast agents used in PAI obstructs its clinical applications. In this study, we developed indocyanine green (ICG)-encapsulated micelles specific for the CD 44 receptor and used in near infrared and photoacoustic imaging of tumors. ICG was hydrophobically modified prior to loading into hyaluronic acid (HA)-based micelles utilized for CD 44 based-targeting. We investigated the physicochemical characteristics of prepared HA only and ICG-encapsulated HA micelles (HA-ICG micelles). After intravenous injection of tumor-bearing mice, the bio-distribution and in vivo photoacoustic images of ICG-encapsulated HA micelles accumulating in tumors were also investigated. Our study further encourages the application of this HA-ICG-based nano-platform as a tumor-specific contrast agent for PAI.

  10. Tuning intermicellar potential of Triton X-100– anthranilic acid mixed micelles

    Gunjan Verma; V K Aswal; S K Kulshreshtha; C Manohar; P A Hassan; Eric W Kaler


    Structural parameters of micelles formed by Triton X-100 in the presence of solubilized anthranilic acid at different pH values was investigated using light scattering and small angle neutron scattering. Analysis of the SANS data indicate that micelles are oblate ellipsoidal in nature with little variation in the dimensions, in the investigated pH range (from 0.5 to 6.0). The interaction potential of the micelles shows a minimum closer to the isoelectric point of anthranilic acid. A similar variation is observed in the cloud point of the micelles with pH. The observed variation in the interaction potential with pH of the micellar solution can be explained in terms of the reversal of charge on anthranilic acid due to shift in the acid–base equilibrium. The variation in interaction potential and cloud point with pH is modelled using Coulombic repulsion of charged molecules at the micelle interface.

  11. Effective repair of traumatically injured spinal cord by nanoscale block copolymer micelles.

    Shi, Yunzhou; Kim, Sungwon; Huff, Terry B; Borgens, Richard B; Park, Kinam; Shi, Riyi; Cheng, Ji-Xin


    Spinal cord injury results in immediate disruption of neuronal membranes, followed by extensive secondary neurodegenerative processes. A key approach for repairing injured spinal cord is to seal the damaged membranes at an early stage. Here, we show that axonal membranes injured by compression can be effectively repaired using self-assembled monomethoxy poly(ethylene glycol)-poly(d,l-lactic acid) di-block copolymer micelles. Injured spinal tissue incubated with micelles (60 nm diameter) showed rapid restoration of compound action potential and reduced calcium influx into axons for micelle concentrations much lower than the concentrations of polyethylene glycol, a known sealing agent for early-stage spinal cord injury. Intravenously injected micelles effectively recovered locomotor function and reduced the volume and inflammatory response of the lesion in injured rats, without any adverse effects. Our results show that copolymer micelles can interrupt the spread of primary spinal cord injury damage with minimal toxicity.

  12. Crafting threads of diblock copolymer micelles via flow-enabled self-assembly.

    Li, Bo; Han, Wei; Jiang, Beibei; Lin, Zhiqun


    Hierarchically assembled amphiphilic diblock copolymer micelles were exquisitely crafted over large areas by capitalizing on two concurrent self-assembling processes at different length scales, namely, the periodic threads composed of a monolayer or a bilayer of diblock copolymer micelles precisely positioned by flow-enabled self-assembly (FESA) on the microscopic scale and the self-assembly of amphiphilic diblock copolymer micelles into ordered arrays within an individual thread on the nanometer scale. A minimum spacing between two adjacent threads λmin was observed. A model was proposed to rationalize the relationship between the thread width and λmin. Such FESA of diblock copolymer micelles is remarkably controllable and easy to implement. It opens up possibilities for lithography-free positioning and patterning of diblock copolymer micelles for various applications in template fabrication of periodic inorganic nanostructures, nanoelectronics, optoelectronics, magnetic devices, and biotechnology.

  13. Synthesis of Cross-Linked Polymeric Micelle pH Nanosensors

    Ek, Pramod Kumar; Jølck, Rasmus Irming; Andresen, Thomas Lars


    at the micelle shell using CuAAC results in a stabilized micelle pH nanosensor. Compared to the postmicelle modification strategy, the mixed-micellization approach increases the control of the overall composition of the nanosensors.Both approaches provide stable nanosensors with similar pKa profiles and thereby......The design flexibility that polymeric micelles offer in the fabrication of optical nanosensors for ratiometric pH measurements is investigated. pH nanosensors based on polymeric micelles are synthesized either by a mixed-micellization approach or by a postmicelle modification strategy. In the mixed......-micellization approach, self-assembly of functionalized unimers followed by shell cross-linking by copper-catalyzed azide-alkyne cycloaddition (CuAAC) results in stabilized cRGD-functionalized micelle pH nanosensors. In the postmicelle modification strategy, simultaneous cross-linking and fluorophore conjugation...

  14. Effect of presence of benzene ring in surfactant hydrophobic chain on the transformation towards one dimensional aggregate

    Rabah A. Khalil


    Full Text Available The formation of wormlike micelle and the following significant changes in rheological properties suffer misunderstanding from both theoretical and fundamental aspects. Recently, we have introduced a theory for interpreting such important phenomenon which is referred to as critical intermolecular forces (CIF. The theory has stated that the hydrophobic effect is the main factor for the formation of worm-like aggregates. Therefore, it seems interesting to check out the validity of this new physical insight through investigating the presence of benzene ring as less hydrophobic group in contrast to that of alkyl in surfactant tail. The mixture of anionic sodium dodecylbenzenesulphonate (SDBS and cationic cetyltrimethylammonium bromide (CTAB shows a high dynamic viscosity peak at the ratio of 80/20 of 3 wt.% CTAB/SDBS indicating the formation of wormlike micelles. The thermodynamic properties have been evaluated for this mixture exhibiting good agreement with the rheological changes. Interestingly, the results show the presence of benzene ring (in SDBS causing a negative effect towards the formation of one dimensional aggregate in contrast to previous results which support the proposed CIF theory. The presence of nonionic surfactant TritonX-100 in binary and ternary systems of SDBS and CTAB prohibits the formation of wormlike micelles.

  15. Proteins aggregation and human diseases

    Hu, Chin-Kun


    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  16. Analysis of Aggregation Delay for Multisource Sensor Data with On-Off Traffic Pattern in Wireless Body Area Networks

    Kim, Un-Ha; Kong, Eutteum; Choi, Hyun-Ho; Lee, Jung-Ryun


    Data aggregation plays an important role to improve the transmission efficiency in wireless body area networks (WBANs); however, it inherently induces additional aggregation delay. Therefore, the effect of packet aggregation on WBAN applications, which are vulnerable to delay, must be analyzed rigorously. In this paper, we analyze the packet aggregation delay for multisource sensor data with an on-off traffic pattern in WBANs. Considering two operational parameters of the aggregation threshold and aggregation timer, we calculate the probability that a packet aggregation occurs during a unit time and then derive the average aggregation delay in closed-form. The analysis results show that the aggregation delay increases as the aggregation timer or aggregation threshold increases, but is bounded below a certain level according to the number of active sensors and their on-off traffic attribute. This implies that the data aggregation technique can maximize the transmission efficiency while satisfying a given delay requirement in the WBAN system. PMID:27706029

  17. Curcumin-loaded biodegradable polymeric micelles for colon cancer therapy in vitro and in vivo

    Gou, Maling; Men, Ke; Shi, Huashan; Xiang, Mingli; Zhang, Juan; Song, Jia; Long, Jianlin; Wan, Yang; Luo, Feng; Zhao, Xia; Qian, Zhiyong


    Curcumin is an effective and safe anticancer agent, but its hydrophobicity inhibits its clinical application. Nanotechnology provides an effective method to improve the water solubility of hydrophobic drug. In this work, curcumin was encapsulated into monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles through a single-step nano-precipitation method, creating curcumin-loaded MPEG-PCL (Cur/MPEG-PCL) micelles. These Cur/MPEG-PCL micelles were monodisperse (PDI = 0.097 +/- 0.011) with a mean particle size of 27.3 +/- 1.3 nm, good re-solubility after freeze-drying, an encapsulation efficiency of 99.16 +/- 1.02%, and drug loading of 12.95 +/- 0.15%. Moreover, these micelles were prepared by a simple and reproducible procedure, making them potentially suitable for scale-up. Curcumin was molecularly dispersed in the PCL core of MPEG-PCL micelles, and could be slow-released in vitro. Encapsulation of curcumin in MPEG-PCL micelles improved the t1/2 and AUC of curcuminin vivo. As well as free curcumin, Cur/MPEG-PCL micelles efficiently inhibited the angiogenesis on transgenic zebrafish model. In an alginate-encapsulated cancer cell assay, intravenous application of Cur/MPEG-PCL micelles more efficiently inhibited the tumor cell-induced angiogenesisin vivo than that of free curcumin. MPEG-PCL micelle-encapsulated curcumin maintained the cytotoxicity of curcumin on C-26 colon carcinoma cellsin vitro. Intravenous application of Cur/MPEG-PCL micelle (25 mg kg-1curcumin) inhibited the growth of subcutaneous C-26 colon carcinoma in vivo (p colon carcinoma through inhibiting angiogenesis and directly killing cancer cells.

  18. PEG-OCL micelles for quercetin solubilization and inhibition of cancer cell growth.

    Khonkarn, Ruttiros; Mankhetkorn, Samlee; Hennink, Wim E; Okonogi, Siriporn


    In this study, quercetin (QCT), a flavonoid with high anticancer potential, was loaded into polymeric micelles of PEG-OCL (poly(ethylene glycol)-b-oligo(ε-caprolactone)) with naphthyl or benzyl end groups in order to increase its aqueous solubility. The cytostatic activity of the QCT-loaded micelles toward different human cancer cell lines and normal cells was investigated. The results showed that the solubility of QCT entrapped in mPEG750-b-OCL micelles was substantially increased up to 1 mg/ml, which is approximately 110 times higher than that of its solubility in water (9 μg/ml). The average particle size of QCT-loaded micelles ranged from 14 to 19 nm. The QCT loading capacity of the polymeric micelles with naphthyl groups was higher than that with benzyl groups (10% and 6%, respectively). QCT-loaded, benzyl- and naphthyl-modified micelles effectively inhibited the growth of both sensitive and resistance cancer cells (human erythromyelogenous leukemia cells (K562) and small lung carcinoma cells (GLC4)). However, the benzyl-modified micelles have a good cytocompatibility (in the concentration range investigated (up to 100 μg/ml), they are well tolerated by living cells), whereas their naphthyl counterparts showed some cytotoxicity at higher concentrations (60-100 μg/ml). Flow cytometry demonstrated that the mechanism underlying the growth inhibitory effect of QCT in its free form was inducing cell cycle arrest at the G2/M phase. Benzyl-modified micelles loaded with QCT also exhibited this cycle arresting the effect of cancer cells. In conclusion, this paper shows the enhancement of solubility and cell cycle arrest of QCT loaded into micelles composed of mPEG750-b-OCL modified with benzyl end groups. These micelles are therefore considered to be an attractive vehicle for the (targeted) delivery of QCT to tumors.

  19. Structure and Dynamics of Nonionic Surfactant Aggregates in Layered Materials.

    Guégan, Régis; Veron, Emmanuel; Le Forestier, Lydie; Ogawa, Makoto; Cadars, Sylvian


    The aggregation of surfactants on solid surfaces as they are adsorbed from solution is the basis of numerous technological applications such as colloidal stabilization, ore flotation, and floor cleaning. The understanding of both the structure and the dynamics of surfactant aggregates applies to the development of alternative ways of preparing hybrid layered materials. For this purpose, we study the adsorption of the triethylene glycol mono n-decyl ether (C10E3) nonionic surfactant onto a synthetic montmorillonite (Mt), an aluminosilicate clay mineral for organoclay preparation with important applications in materials sciences, catalysis, wastewater treatment, or as drug delivery. The aggregation mechanisms follow those observed in an analogous natural Mt, with the condensation of C10E3 in a bilayer arrangement once the surfactant self-assembles in a lamellar phase beyond the critical micelle concentration, underlining the importance of the surfactant state in solution. Solid-state (1)H nuclear magnetic resonance (NMR) at fast magic-angle spinning (MAS) and high magnetic field combined with(1)H-(13)C correlation experiments and different types of (13)C NMR experiments selectively probes mobile or rigid moieties of C10E3 in three different aggregate organizations: (i) a lateral monolayer, (ii) a lateral bilayer, and (iii) a normal bilayer. High-resolution (1)H{(27)Al} CP-(1)H-(1)H spin diffusion experiments shed light on the proximities and dynamics of the different fragments and fractions of the intercalated surfactant molecules with respect to the Mt surface. (23)Na and (1)H NMR measurements combined with complementary NMR data, at both molecular and nanometer scales, precisely pointed out the location of the C10E3 ethylene oxide hydrophilic group in close contact with the Mt surface interacting through ion-dipole or van der Waals interactions.

  20. Topological data analysis of biological aggregation models.

    Topaz, Chad M; Ziegelmeier, Lori; Halverson, Tom


    We apply tools from topological data analysis to two mathematical models inspired by biological aggregations such as bird flocks, fish schools, and insect swarms. Our data consists of numerical simulation output from the models of Vicsek and D'Orsogna. These models are dynamical systems describing the movement of agents who interact via alignment, attraction, and/or repulsion. Each simulation time frame is a point cloud in position-velocity space. We analyze the topological structure of these point clouds, interpreting the persistent homology by calculating the first few Betti numbers. These Betti numbers count connected components, topological circles, and trapped volumes present in the data. To interpret our results, we introduce a visualization that displays Betti numbers over simulation time and topological persistence scale. We compare our topological results to order parameters typically used to quantify the global behavior of aggregations, such as polarization and angular momentum. The topological calculations reveal events and structure not captured by the order parameters.

  1. Molecular exchange in block copolymer micelles: when corona chains overlap

    Lu, Jie; Lodge, Timothy; Bates, Frank; Choi, Soohyung


    The chain exchange kinetics of poly(styrene-b-ethylenepropylene) (PS-PEP) diblock copolymer micelles in squalane (C30H62) was investigated using time-resolved small angle neutron scattering (TR-SANS). The solvent is a mixture of h-squalane and d-squalane that contrast-matches a mixed 50/50 h/d PS micelle core. As isotope labeled chains exchange, the core contrast decreases, leading to a reduction in scattering intensity. This strategy therefore allows direct probing of the chain exchange rate. Separate copolymer micellar solutions containing either deuterium labeled (dPS) or normal (hPS) poly(styrene) core blocks were prepared and mixed at room temperature, below the core glass transition temperature. The samples were heated to several temperatures (around 100 °C) and monitored by TR-SANS every 5 min. As polymer concentration was increased from 1% to 15% by volume, we observed a significant slowing down of chain exchange rate. Similar retarded kinetics was found when part of the solvent in the 1% solution was replaced by homopolymer PEP (comparable size as corona block). Furthermore, if all the solvent is replaced with PEP, no exchange was detected for up to 3hr at 200 °C. These results will be discussed in terms of a molecular model for chain exchange Infineum, Iprime, NIST, ORNL

  2. Modulation of ROS production in human leukocytes by ganglioside micelles

    M. Gavella


    Full Text Available Recent studies have reported that exogenous gangliosides, the sialic acid-containing glycosphingolipids, are able to modulate many cellular functions. We examined the effect of micelles of mono- and trisialoganglioside GM1 and GT1b on the production of reactive oxygen species by stimulated human polymorphonuclear neutrophils using different spectroscopic methods. The results indicated that exogenous gangliosides did not influence extracellular superoxide anion (O2.- generation by polymorphonuclear neutrophils activated by receptor-dependent formyl-methionyl-leucyl-phenylalanine. However, when neutrophils were stimulated by receptor-bypassing phorbol 12-myristate 13-acetate (PMA, gangliosides above their critical micellar concentrations prolonged the lag time preceding the production in a concentration-dependent way, without affecting total extracellular O2.- generation detected by superoxide dismutase-inhibitable cytochrome c reduction. The effect of ganglioside GT1b (100 µM on the increase in lag time was shown to be significant by means of both superoxide dismutase-inhibitable cytochrome c reduction assay and electron paramagnetic resonance spectroscopy (P < 0.0001 and P < 0.005, respectively. The observed phenomena can be attributed to the ability of ganglioside micelles attached to the cell surface to slow down PMA uptake, thus increasing the diffusion barrier and consequently delaying membrane events responsible for PMA-stimulated O2.- production.

  3. Encapsulation of GFP in Complex Coacervate Core Micelles.

    Nolles, Antsje; Westphal, Adrie H; de Hoop, Jacob A; Fokkink, Remco G; Kleijn, J Mieke; van Berkel, Willem J H; Borst, Jan Willem


    Protein encapsulation with polymers has a high potential for drug delivery, enzyme protection and stabilization. Formation of such structures can be achieved by the use of polyelectrolytes to generate so-called complex coacervate core micelles (C3Ms). Here, encapsulation of enhanced green fluorescent protein (EGFP) was investigated using a cationic-neutral diblock copolymer of two different sizes: poly(2-methyl-vinyl-pyridinium)41-b-poly(ethylene-oxide)205 and poly(2-methyl-vinyl-pyridinium)128-b-poly(ethylene-oxide)477. Dynamic light scattering and fluorescence correlation spectroscopy (FCS) revealed a preferred micellar composition (PMC) with a positive charge composition of 0.65 for both diblock copolymers and micellar hydrodynamic radii of approximately 34 nm. FCS data show that at the PMC, C3Ms are formed above 100 nM EGFP, independent of polymer length. Mixtures of EGFP and nonfluorescent GFP were used to quantify the amount of GFP molecules per C3M, resulting in approximately 450 GFPs encapsulated per micelle. This study shows that FCS can be successfully applied for the characterization of protein-containing C3Ms.

  4. Compound exocytosis of casein micelles in mammary epithelial cells.

    Dylewski, D P; Keenan, T W


    Ultrastructure of lactating bovine and rat mammary epithelial cells was studied with emphasis on secretory vesicle interactions. In the apical zone of the cell, adjacent secretory vesicles formed ball and socket configurations at their points of apposition. Similar configurations were formed between plasma membrane and secretory vesicle membrane. These structures may be formed by the diffusion of water between vesicles with different osmotic potentials. Frequently, vesicular chains consisting of 10 or more linked secretory vesicles were observed. Prior to the exocytotic release of casein micelles, adjacent vesicles fused through fragmentation of the ball and socket membrane. These membrane fragments and the casein micelles appeared to be secreted into the alveolar lumen after passing from one vesicle into another and finally through a pore in the apical plasma membrane. Emptied vesicular chains appeared to collapse and fragmentation of their membrane was observed. Based on these observations, we suggest that most vesicular membrane does not directly contact or become incorporated into the plasma membrane during secretion of the nonfat phase of milk.

  5. Micelle assisted structural conversion with fluorescence modulation of benzophenanthridine alkaloids

    Pradhan, Ankur Bikash; Bhuiya, Sutanwi; Haque, Lucy; Tiwari, Richa; Das, Suman


    In this study we have reported the anionic surfactant (Sodium dodecyl sulfate, SDS) driven structural conversion of two benzophenanthridine plant alkaloids namely Chelerythrine (herein after CHL) and Sanguinarine (herein after SANG). Both the alkaloids exist in two forms: the charged iminium and the neutral alkanolamine form. The iminium form is stable at low pH ( 10.1). The fluorescence intensity of the alkanolamine form is much stronger than the iminium form. The iminium form of both the alkaloids remains stable whereas the alkanolamine form gets converted to the iminium form in the SDS micelle environment. The iminium form possesses positive charge and it seems that electrostatic interaction between the positively charged iminium and negatively charged surfactant leads to the stabilization of the iminium form in the Stern layer of the anionic micelle. Whereas the conversion of the alkanolamine form into the iminium form takes place and that can be monitored in naked eye since the iminium form is orange in colour and the alkanolamine form has blue violet emission. Such a detail insight about the photophysical properties of the benzophenanthridine alkaloids would be a valuable addition in the field of alkaloid-surfactant interaction.

  6. Wormlike micelles in mixed amino acid surfactant/nonionic surfactant aqueous systems and the effect of added electrolytes.

    Shrestha, Rekha Goswami; Rodriguez-Abreu, Carlos; Aramaki, Kenji


    The formation of viscoelastic wormlike micelles in mixed amino acid surfactant/nonionic surfactant aqueous systems in the presence of different counterions and salts is reported, and the effects of the different electrolytes on the rheological behavior are discussed. N-dodecanoylglutamic acid (LAD) is neutralized with biologically relevant L-lysine and L-arginine to obtain anionic surfactants (LAD-Lys2, LAD-Arg2) which form aqueous micellar solutions at 25 degrees C. Addition of a nonionic surfactant, tri-ethyleneglycol mono n-tetradecyl ether (C14EO3), to the aqueous solutions of both LAD-Lys2 and LAD-Arg2 causes the zero-shear viscosity (eta(0)) to increase with C14EO3 concentration gradually at first, and then sharply, indicating one-dimensional growth of the aggregates and eventual formation of entangled wormlike micelles. Further addition of C14EO3 ultimately leads to phase separation of liquid crystals. Such a phase separation, which limits the maximum attainable viscosity, takes place at lower C14EO3 concentrations for LAD-Lys2 compared to LAD-Arg2 systems. It was found that the rheological behavior of micellar solutions is significantly affected by the addition of Na+X(-) salts (X = Cl(-), Br(-), I(-), NO3(-)). The maximum viscosities obtained for the systems with added salt are all higher than that of the salt-free system, and the onset of wormlike micelle formation shift towards lower nonionic surfactant concentrations upon addition of electrolyte. The maximum attainable thickening effect of anions increases in the order NO3(-)>I(-)>Br(-)>Cl(-). The effect of temperature was also investigated. Phase separation takes place at certain temperature, which depends on the type of anion in the added salt, and decreases in the order I(-)>NO3(-)>Br(-) approximately equal Cl(-), in agreement with Hofmeister's series in terms of amphiphile solubility. The thermoresponsive rheological behavior was also found to be highly dependent on the type of anion, and anomalous

  7. Hydrophobic aggregation of ultrafine kaolinite

    ZHANG Xiao-ping; HU Yue-hua; LIU Run-Qing


    The hydrophobic aggregation of ultrafine kaolinite in cationic surfactant suspension was investigated by sedimentation test, zeta potential measurement and SEM observation. SEM images reveal that kaolinite particles show the self-aggregation of edge-face in acidic media, the aggregation of edge-face and edge-edge in neutral media, and the dispersion in alkaline media due to electrostatic repulsion. In the presence of the dodecylammonium acetate cationic surfactant and in neutral and alkaline suspension, the hydrophobic aggregation of face-face is demonstrated. The zeta potential of kaolinite increases with increasing the concentration of cationic surfactant. The small and loose aggregation at a low concentration but big and tight aggregation at a high concentration is presented At pH=7 alkyl quarterly amine salt CTAB has the best hydrophobic aggregation among three cationic surfactants, namely, dodecylammonium acetate, alkyl quarterly amine salts 1227 and CTAB.

  8. Absorption Spectra of Astaxanthin Aggregates

    Olsina, Jan; Minofar, Babak; Polivka, Tomas; Mancal, Tomas


    Carotenoids in hydrated polar solvents form aggregates characterized by dramatic changes in their absorption spectra with respect to monomers. Here we analyze absorption spectra of aggregates of the carotenoid astaxanthin in hydrated dimethylsulfoxide. Depending on water content, two types of aggregates were produced: H-aggregates with absorption maximum around 390 nm, and J-aggregates with red-shifted absorption band peaking at wavelengths >550 nm. The large shifts with respect to absorption maximum of monomeric astaxanthin (470-495 nm depending on solvent) are caused by excitonic interaction between aggregated molecules. We applied molecular dynamics simulations to elucidate structure of astaxanthin dimer in water, and the resulting structure was used as a basis for calculations of absorption spectra. Absorption spectra of astaxanthin aggregates in hydrated dimethylsulfoxide were calculated using molecular exciton model with the resonance interaction energy between astaxanthin monomers constrained by semi-e...

  9. Non-Arrhenius protein aggregation.

    Wang, Wei; Roberts, Christopher J


    Protein aggregation presents one of the key challenges in the development of protein biotherapeutics. It affects not only product quality but also potentially impacts safety, as protein aggregates have been shown to be linked with cytotoxicity and patient immunogenicity. Therefore, investigations of protein aggregation remain a major focus in pharmaceutical companies and academic institutions. Due to the complexity of the aggregation process and temperature-dependent conformational stability, temperature-induced protein aggregation is often non-Arrhenius over even relatively small temperature windows relevant for product development, and this makes low-temperature extrapolation difficult based simply on accelerated stability studies at high temperatures. This review discusses the non-Arrhenius nature of the temperature dependence of protein aggregation, explores possible causes, and considers inherent hurdles for accurately extrapolating aggregation rates from conventional industrial approaches for selecting accelerated conditions and from conventional or more advanced methods of analyzing the resulting rate data.

  10. Simultaneous optimization of variables influencing selectivity and elution strength in micellar liquid chromatography. Effect of organic modifier and micelle concentration.

    Strasters, J K; Breyer, E D; Rodgers, A H; Khaledi, M G


    Previously, the simultaneous enhancement of separation selectivity with elution strength was reported in micellar liquid chromatography (MLC) using the hybrid eluents of water-organic solvent-micelles. The practical implication of this phenomenon is that better separations can be achieved in shorter analysis times by using the hybrid eluents. Since both micelle concentration and volume fraction of organic modifier influence selectivity and solvent strength, only an investigation of the effects of a simultaneous variation of these parameters will disclose the full separation capability of the method, i.e. the commonly used sequential solvent optimization approach of adjusting the solvent strength first and then improving selectivity in reversed-phase liquid chromatography is inefficient for the case of MLC with the hybrid eluents. This is illustrated in this paper with two examples: the optimization of the selectivity in the separation of a mixture of phenols and the optimization of a resolution-based criterion determined for the separation of a number of amino acids and small peptides. The large number of variables involved in the separation process in MLC necessitates a structured approach in the development of practical applications of this technique. A regular change in retention behavior is observed with the variation of the surfactant concentration and the concentration of organic modifier, which enables a successful prediction of retention times. Consequently interpretive optimization strategies such as the interative regression method are applicable.

  11. The impact of the confinement of reactants on the metal distribution in bimetallic nanoparticles synthesized in reverse micelles

    Concha Tojo


    Full Text Available A kinetic study on the formation of bimetallic nanoparticles in microemulsions was carried out by computer simulation. A comprehensive analysis of the resulting nanostructures was performed regarding the influence of intermicellar exchange on reactivity. The objects of this study were metals having a difference in standard reduction potential of about 0.2–0.3 V. Relatively flexible microemulsions were employed and the concentration of the reactants was kept constant, while the reaction rate of each metal was monitored as a function of time using different reactant proportions. It was demonstrated that the reaction rates depend not only on the chemical reduction rate, but also on the intermicellar exchange rate. Furthermore, intermicellar exchange causes the accumulation of slower precursors inside the micelles, which favors chemical reduction. As a consequence, slower reduction rates strongly correlate with the number of reactants in this confined media. On the contrary, faster reduction rates are limited by the intermicellar exchange rate and not the number of reactants inside the micelles. As a result, different precursor proportions lead to different sequences of metal reduction, and thus the arrangement of the two metals in the nanostructure can be manipulated.

  12. A Glimpse of Our Journey into the Design of Optical Probes in Self-assembled Surfactant Aggregates.

    Dey, Nilanjan; Bhattacharya, Santanu


    Dynamic self-assembling amphiphilic surfactant molecules, popularly known as "micelles", have received widespread attention, due to their ability to modulate the photophysical properties of various organic dyes upon encapsulation. Along with their well-known use as cleaning agents, catalysts in organic reactions, and even for drug delivery purposes, these surfactant assemblies also show promising pertinence in the recognition of both ionic and nonionic targeted analytes. Low micropolarity and relatively hydrophobic environments promote their interaction with ionic analytes, whereas neutral species mostly affect the aggregation pattern of the probe molecules upon partitioning inside the micellar hydrophobic milieu. The environment-sensitive nature of micelle-based self-assembled probes also prompts us to devise new sensor arrays for the recognition of multiple analytes. While this account will largely focus on our own work in developing surfactant-triggered self-assembled sensors, our findings have been placed in the context of the relevant contributions from others during their strategic evolution.

  13. Zwitterionic and mesoionic liquids:Molecular aggregation in 3-methylsydnone

    CASSEL; Stéphanie; RICO-LATTES; Isabelle; LATTES; Armand


    Ionic liquids are green solvents with interesting properties:displaying low melting points and high boiling points.They offer a new approach applicable in many instances.Nevertheless,the presence of free ions can be a matter in some cases,e.g.for the study of nucleophilic reactions,in electrochemistry,and in each situation where there is a competition between counter ions,as in micellization of ionic surfactants.Neutral compounds having formal unit electrical charges of opposite sign,and the same physical properties than ionic liquids would be a nice alternative to these latter solvents.There are two classes of chemical compounds having these characteristics:zwitterionic liquids(with no uncharged canonical representation) and mesoionic liquids(in which the negative and the positive charges are delocalized).In that last class we have chosen to work with 3-methylsydnone in order to examine,in this aprotic solvent,if it was possible to observe aggregation of surfactants in the same manner as in water.With all kinds of surfactants studied(ionic,zwitterionic and mesoionic) we have been able to demonstrate the formation of direct micelles:hydrogen bonding is thus not mandatory for molecular aggregation.Comparison of the behavior in water and in formamide showed that solvophobic interactions were qualitatively comparable but with a lower intensity.

  14. Adsorption characteristics of uranyl ions onto micelle surface for treatment of radioactive liquid wastes by micelle enhanced ultrafiltration technique

    Lee, K. W.; Choi, W. K.; Jeong, K. H.; Lee, D. K.; Jeong, K. J. [KAERI, Taejon (Korea, Republic of)


    The objective of this investigation is to establish the rejection behavior of uranium bearing waste water by micelle enhanced ultrafiltration technique. An extensive experimental investigation was conducted with uranium only and uranium in the presence of electrolyte, utilizing ultrasfiltration stirred cell. The effects of experimental parameters such as solution pH and concentration of uranium on rejection were examined from the change of micelle concentration. The rejection dependence of the uranium was found to be a function of pH and uranium to surfactant concentration ratio. Over 95% removal was observed at pH 3 {approx} 5 and SDS concentration of 40 mM. In the presence of electrolytes, the rejection of uranium was observed to decrease significantly, the addition of cobalt ion showed more reduction than that obtained by presence of sodium and cesium ions on rejection of uranium. The rejection behavior was explained in terms of apparent distribution constants. The rejection efficiencies of uranyl ions was significantly affected by the chemical species of the given system. For all cases, the rejection was highly dependent on uranium complex species.

  15. Research on Judgment Aggregation Based on Logic

    Li Dai


    Full Text Available Preference aggregation and judgment aggregation are two basic research models of group decision making. And preference aggregation has been deeply studied in social choice theory. However, researches of social choice theory gradually focus on judgment aggregation which appears recently. Judgment aggregation focuses on how to aggregate many consistent logical formulas into one, from the perspective of logic. We try to start with judgment aggregation model based on logic and then explore different solutions to problem of judgment aggregation.

  16. Optimal aggregation of noisy observations: A large deviations approach

    Murayama, Tatsuto; Davis, Peter, E-mail:, E-mail: [NTT Communication Science Laboratories, NTT Corporation, 2-4, Hikaridai, Seika-cho, Keihanna, Kyoto 619-0237 (Japan)


    Sensing and data aggregation tasks in distributed systems should not be considered as separate issues. The quality of collective estimation involves a fundamental tradeoff between sensing quality, which can be increased by increasing the number of sensors, and aggregation quality under a given capacity of the network, which decreases if the number of sensors is too large. In this paper, we examine a system level strategy for optimal aggregation of data from an ensemble of independent sensors. In particular, we consider large scale aggregation from very many sensors, in which case the network capacity diverges to infinity. Then, by applying the large deviations techniques, we conclude the following significant result: larger scale aggregation always outperforms smaller scale aggregation at higher noise levels, while below a critical value of noise, there exist moderate scale aggregation levels at which optimal estimation is realized. At a critical value of noise, there is an abrupt change in the behavior of a parameter characterizing the aggregation strategy, similar to a phase transition in statistical physics.

  17. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Yu Lu


    Full Text Available Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles.

  18. Spectral Properties and Solubilization Location of 2'-Ethylhexyl 4-(N,N-Dimethylamino)benzoate in Micelles

    Ning Ding; Xin-zhen Du; Chun Wang; Xiao-quan Lu


    Dual fluorescence and UV absorption of 2'-ethylhexyl 4-(N,N-dimethylamino)benzoate (EHDMAB) were investigated in cationic,non-ionic and anionic miceUes.When EHDMAB was solubilized in different micellss, the UV absorption of EHDMAB was enhanced.Twisted intramolecular charge transfer (TICT) emission with longer wavelength was observed in ionic micelles,whereas TICT emission with shorter wavelength was obtained in non-ionic micelles.In particular,dual fluorescence of EHDMAB was significantly quenched by the positively charged pyridinium ions arranged in the Stern layer of cationic micelles.UV radiation absorbed mainly decays via TICT emission and radiationless deactivation.The dimethylamino group of EHDMAB experiences different polar environments in ionic and non-ionic micelles according to the polarity dependence of TICT emission of EHDMAB in organic solvents.In terms of the molecular structures and sizes of EHDMAB and surfactants,each individual EHDMAB molecule should be buried in micelles with its dimethylamino group toward the polar head groups of different micelles and with its 2'-ethylhexyl chain toward the hydrophobic micellar core.Dynamic fluorescence quenching measurements of EHDMAB provide further support for the location of EHDMAB in different micelles.

  19. A micelle-like structure of poloxamer-methotrexate conjugates as nanocarrier for methotrexate delivery.

    Ren, Jin; Fang, Zhengjie; Yao, Li; Dahmani, Fatima Zohra; Yin, Lifang; Zhou, Jianping; Yao, Jing


    The purpose of this study was to develop a novel featured and flexible methotrexate (MTX) formulation, in which MTX was physically entrapped and chemically conjugated in the same drug delivery system. A series of poloxamer-MTX (p-MTX) conjugates was synthesized, wherein MTX was grafted to poloxamer through an ester bond. p-MTX conjugates could self-assemble into micelle-like structures in aqueous environment and the MTX end was in the inner-core of micelles. Moreover, free MTX could be physically entrapped into p-MTX micelles hydrophobic core region to increase the total drug loading. Importantly, the resulting MTX-loaded p-MTX micelles showed a biphasic release of MTX, with a relative fast release of the entrapped MTX (about 6-7h) followed by a sustained release of the conjugated MTX. The pharmacokinetics study showed that the mean residence time (MRT) was extended in the case of MTX-loaded p-MTX micelles, indicating a delayed MTX elimination from the bloodstream and prolonged in vivo residence time. Besides, the area under curve (AUC) of MTX-loaded p-MTX micelles was greater than free MTX, indicating a drug bioavailability improvement. Overall, MTX-loaded p-MTX micelles might be a promising nanosized drug delivery system for the cancer therapy.

  20. Thermo-sensitive complex micelles from sodium alginate-graft-poly(N-isopropylacrylamide) for drug release.

    Yu, Nana; Li, Guiying; Gao, Yurong; Jiang, Hua; Tao, Qian


    Polymer micelles with environmentally sensitive properties have potential applications in biomedicine. In this paper, thermo-sensitive complex micelles assembled from biocompatible graft copolymers sodium alginate-graft-poly(N-isopropylacrylamide) (SA-g-PNIPAM) and divalent metal ions were prepared for controlled drug release. The polymer micelles had core-corona structure, which was constituted by metal ions (Ba(2+), Zn(2+), Co(2+)) cross-linked sodium alginate as the core and thermo-sensitive PNIPAM chains as the corona. Formation of polymer micelles was determined by Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). The polymer micelles were observed as regular spheres with good polydispersity and excellent performance on drug encapsulation and release ability. The cumulative release of 5-fluorouracil (5-FU) from micelles was controlled by pH, ionic strength or temperature of surroundings. The superior properties of sensitive polymer micelles induced by metal ions are expected to be utilized in controlled drug delivery systems.

  1. Bone-targeted acid-sensitive doxorubicin conjugate micelles as potential osteosarcoma therapeutics.

    Low, Stewart A; Yang, Jiyuan; Kopeček, Jindřich


    Osteosarcoma is a malignancy of the bone that primarily affects adolescents. Current treatments retain mortality rates, which are higher than average cancer mortality rates for the adolescent age group. We designed a micellar delivery system with the aim to increase drug accumulation in the tumor and potentially reduce side effects associated with chemotherapy. The design features are the use of the hydrophilic D-aspartic acid octapeptide as both the effective targeting agent as well as the hydrophilic micelle corona. Micelle stabilization was accomplished by binding of model drug (doxorubicin) via an acid-sensitive hydrazone bond and incorporating one to four 11-aminoundecanoic acid (AUA) moieties to manipulate the hydrophobic/hydrophilic ratio. Four micelle-forming unimers have been synthesized and their self-assembly into micelles was evaluated. Size of the micelles could be modified by changing the architecture of the unimers from linear to branched. The stability of the micelles increased with increasing content of AUA moieties. Adsorption of all micelles to hydroxyapatite occurred rapidly. Doxorubicin release occurred at pH 5.5, whereas no release was detected at pH 7.4. Cytotoxicity toward human osteosarcoma Saos-2 cells correlated with drug release data.

  2. Production of Fluconazole-Loaded Polymeric Micelles Using Membrane and Microfluidic Dispersion Devices

    Lu, Yu; Chowdhury, Danial; Vladisavljević, Goran T.; Koutroumanis, Konstantinos; Georgiadou, Stella


    Polymeric micelles with a controlled size in the range between 41 and 80 nm were prepared by injecting the organic phase through a microengineered nickel membrane or a tapered-end glass capillary into an aqueous phase. The organic phase was composed of 1 mg·mL−1 of PEG-b-PCL diblock copolymers with variable molecular weights, dissolved in tetrahydrofuran (THF) or acetone. The pore size of the membrane was 20 μm and the aqueous/organic phase volumetric flow rate ratio ranged from 1.5 to 10. Block copolymers were successfully synthesized with Mn ranging from ~9700 to 16,000 g·mol−1 and polymeric micelles were successfully produced from both devices. Micelles produced from the membrane device were smaller than those produced from the microfluidic device, due to the much smaller pore size compared with the orifice size in a co-flow device. The micelles were found to be relatively stable in terms of their size with an initial decrease in size attributed to evaporation of residual solvent rather than their structural disintegration. Fluconazole was loaded into the cores of micelles by injecting the organic phase composed of 0.5–2.5 mg·mL−1 fluconazole and 1.5 mg·mL−1 copolymer. The size of the drug-loaded micelles was found to be significantly larger than the size of empty micelles. PMID:27231945

  3. Effect of the lipid chain melting transition on the stability of DSPE-PEG(2000) micelles.

    Kastantin, Mark; Ananthanarayanan, Badriprasad; Karmali, Priya; Ruoslahti, Erkki; Tirrell, Matthew


    Micellar nanoparticles are showing promise as carriers of diagnostic and therapeutic biofunctionality, leading to increased interest in their properties and behavior, particularly their size, shape, and stability. This work investigates the physical chemistry of micelles formed from DSPE-PEG(2000) monomers as it pertains to these properties. A melting transition in the lipid core of spheroidal DSPE-PEG(2000) micelles is observed as an endothermic peak at 12.8 degrees C upon heating in differential scanning calorimetry thermograms. Bulky PEG(2000) head groups prevent regular crystalline packing of lipids in both the low-temperature glassy and high-temperature fluid phases, as evidenced by wide-angle X-ray scattering. Equilibrium micelle geometry is spheroidal above and below the transition temperature, indicating that the entropic penalty to force the PEG brush into flat geometry is greater than the enthalpic benefit to the glassy core to pack in an extended configuration. Increased micelle stability is seen in the glassy phase with monomer desorption rates significantly lower than in the fluid phase. Activation energies for monomer desorption are 156+/-6.7 and 79+/-5.0 kJ/mol for the glassy and fluid phases, respectively. The observation of a glass transition that increases micelle stability but does not perturb micelle geometry is useful for the design of more effective biofunctional micelles.

  4. Octreotide-functionalized and resveratrol-loaded unimolecular micelles for targeted neuroendocrine cancer therapy

    Xu, Wenjin; Burke, Jocelyn F.; Pilla, Srikanth; Chen, Herbert; Jaskula-Sztul, Renata; Gong, Shaoqin


    Medullary thyroid cancer (MTC) is a neuroendocrine tumor (NET) that is often resistant to standard therapies. Resveratrol suppresses MTC growth in vitro, but it has low bioavailability in vivo due to its poor water solubility and rapid metabolic breakdown, as well as lack of tumor-targeting ability. A novel unimolecular micelle based on a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for NET-targeted delivery. The hyperbranched amphiphilic block copolymer consisted of a dendritic Boltorn® H40 core, a hydrophobic poly(l-lactide) (PLA) inner shell, and a hydrophilic poly(ethylene glycol) (PEG) outer shell. Octreotide (OCT), a peptide that shows strong binding affinity to somatostatin receptors, which are overexpressed on NET cells, was used as the targeting ligand. Resveratrol was physically encapsulated by the micelle with a drug loading content of 12.1%. The unimolecular micelles exhibited a uniform size distribution and spherical morphology, which were determined by both transmission electron microscopy (TEM) and dynamic light scattering (DLS). Cellular uptake, cellular proliferation, and Western blot analyses demonstrated that the resveratrol-loaded OCT-targeted micelles suppressed growth more effectively than non-targeted micelles. Moreover, resveratrol-loaded NET-targeted micelles affected MTC cells similarly to free resveratrol in vitro, with equal growth suppression and reduction in NET marker production. These results suggest that the H40-based unimolecular micelle may offer a promising approach for targeted NET therapy.

  5. Thermal responsive micelles for dual tumor-targeting imaging and therapy

    Chen, Haiyan; Li, Bowen; Qiu, Jiadan; Li, Jiangyu; Jin, Jing; Dai, Shuhang; Ma, Yuxiang; Gu, Yueqing


    Two kinds of thermally responsive polymers P(FAA-NIPA-co-AAm-co-ODA) and P(FPA-NIPA-co-AAm-co-ODA) containing folate, isopropyl acrylamide and octadecyl acrylate were fabricated through free radical random copolymerization for targeted drug delivery. Then the micelles formed in aqueous solution by self-assembly and were characterized in terms of particle size, lower critical solution temperature (LCST) and a variety of optical spectra. MTT assays demonstrated the low cytotoxicity of the control micelle and drug-loaded micelle on A549 cells and Bel 7402 cells. Then fluorescein and cypate were used as model drugs to optimize the constituents of micelles for drug entrapment efficiency and investigate the release kinetics of micelles in vitro. The FA and thermal co-mediated tumor-targeting efficiency of the two kinds of micelles were verified and compared in detail at cell level and animal level, respectively. These results indicated that the dual-targeting micelles are promising drug delivery systems for tumor-targeting therapy.

  6. Cholesterol-Enhanced Polylactide-Based Stereocomplex Micelle for Effective Delivery of Doxorubicin

    Jixue Wang


    Full Text Available Nanoscale micelles as an effective drug delivery system have attracted increasing interest in malignancy therapy. The present study reported the construction of the cholesterol-enhanced doxorubicin (DOX-loaded poly(D-lactide-based micelle (CDM/DOX, poly(L-lactide-based micelle (CLM/DOX, and stereocomplex micelle (CSCM/DOX from the equimolar enantiomeric 4-armed poly(ethylene glycol–polylactide copolymers in aqueous condition. Compared with CDM/DOX and CLM/DOX, CSCM/DOX showed the smallest hydrodynamic size of 96 ± 4.8 nm and the slowest DOX release. The DOX-loaded micelles exhibited a weaker DOX fluorescence inside mouse renal carcinoma cells (i.e., RenCa cells compared to free DOX·HCl, probably because of a slower DOX release. More importantly, all the DOX-loaded micelles, especially CSCM/DOX, exhibited the excellent antiproliferative efficacy that was equal to or even better than free DOX·HCl toward RenCa cells attributed to their successful internalization. Furthermore, all of the DOX-loaded micelles exhibited the satisfactory hemocompatibility compared to free DOX·HCl, indicating the great potential for systemic chemotherapy through intravenous injection.

  7. Logically Sensing Aggregate Process and Discriminating SDS from Other Surfactants with the Assistance of BSA

    钱俊红; 徐玉芳; 钱旭红


    An amphiphilic fluorescent probe, 3-dodecylamino dihydrogen imidazo[2,l-a]benz[de]isoquinolin-7-one (compound 3), was used to sense the aggregate formation process of bovine serum albumine (BSA), sodium dode- cyl sulfate (SDS) and their mixed system. The fluorescence intensity of 3 was significantly affected by the adding order of SDS and BSA, and SDS can be distinguished from other surfactants with the aid of BSA, but only when 3 is allowed to interact with BSA first. The results revealed that compound 3 is preferentially sited in the hydrophobic region of BSA, and thermodynamically in SDS-BSA mixed aggregate. Sodium phosphate buffer solution (PBS) and BSA played important but distinct roles in distinguishing SDS micelle from the others.

  8. Backbone-hydrazone-containing biodegradable copolymeric micelles for anticancer drug delivery

    Xu, Jing; Luan, Shujuan; Qin, Benkai; Wang, Yingying; Wang, Kai; Qi, Peilan; Song, Shiyong


    Well-defined biodegradable, pH-sensitive amphiphilic block polymers, poly(ethylene glycol)-Hyd-poly(lactic acid) (mPEG-Hyd-PLA) which have acid-cleavable linkages in their backbones, were synthesized via ring-opening polymerization initiated from hydrazone-containing macroinitiators. Introducing a hydrazone bond onto the backbone of an amphiphilic copolymer will find a broad-spectrum encapsulation of hydrophobic drugs. Dynamic light scattering (DLS) and transmission electron microscopy showed that the diblock copolymers self-assembled into stable micelles with average diameters of 100 nm. The mean diameters and size distribution of the hydrazone-containing micelles changed obviously in mildly acidic pH (multiple peaks from 1 to 202 nm appeared under a pH 4.0 condition) than in neutral, while there were no changes in the case of non-sensitive ones. Doxorubicin (DOX) and paclitaxel (PTX) were loaded with drug loading content ranging from 2.4 to 3.5 %, respectively. Interestingly, the anticancer drugs released from mPEG-Hyd-PLA micelles could also be promoted by the increased acidity. An in vitro cytotoxicity study showed that the DOX-loaded mPEG-Hyd-PLA micelles have significantly enhanced cytotoxicity against HepG2 cells compared with the non-sensitive poly(ethylene glycol)-block-poly(lactic acid) (mPEG-PLA) micelles. Confocal microscopy observation indicated that more DOX were delivered into the nuclei of cells following 6 or 12 h incubation with DOX-loaded mPEG-Hyd-PLA micelles. In vivo studies on H22-bearing Swiss mice demonstrated the superior anticancer activity of DOX-loaded mPEG-Hyd-PLA micelles over free DOX and DOX-loaded mPEG-PLA micelles. These hydrazone-containing pH-responsive degradable micelles provide a useful strategy for antitumor drug delivery.

  9. Catalytic performance and thermostability of chloroperoxidase in reverse micelle: achievement of a catalytically favorable enzyme conformation.

    Wang, Yali; Wu, Jinyue; Ru, Xuejiao; Jiang, Yucheng; Hu, Mancheng; Li, Shuni; Zhai, Quanguo


    The catalytic performance of chloroperoxidase (CPO) in peroxidation of 2, 2'-azinobis-(-3 ethylbenzothiazoline-6-sulfononic acid) diammonium salt (ABTS) and oxidation of indole in a reverse micelle composed of surfactant-water-isooctane-pentanol was investigated and optimized in this work. Some positive results were obtained as follows: the peroxidation activity of CPO was enhanced 248% and 263%, while oxidation activity was enhanced 215% and 222% in cetyltrimethylammonium bromide (CTABr) reverse micelle medium and dodecyltrimethylammonium bromide (DTABr) medium, respectively. Thermostability was also greatly improved in reverse micelle: at 40 °C, CPO essentially lost all its activity after 5 h incubation, while 58-76% catalytic activity was retained for both reactions in the two reverse micelle media. At 50 °C, about 44-75% catalytic activity remained for both reactions in reverse micelle after 2 h compared with no observed activity in pure buffer under the same conditions. The enhancement of CPO activity was dependent mainly on the surfactant concentration and structure, organic solvent ratio (V(pentanol)/V(isooctane)), and water content in the reverse micelle. The obtained kinetic parameters showed that the catalytic turnover frequency (k(cat)) was increased in reverse micelle. Moreover, the lower K(m) and higher k(cat)/K(m) demonstrated that both the affinity and specificity of CPO to substrates were improved in reverse micelle media. Fluorescence, circular dichroism (CD) and UV-vis spectra assays indicated that a catalytically favorable conformation of enzyme was achieved in reverse micelle, including the strengthening of the protein α-helix structure, and greater exposure of the heme prosthetic group for easy access of the substrate in bulk solution. These results are promising in view of the industrial applications of this versatile biological catalyst.

  10. Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

    Wang K


    Full Text Available Ke Wang,1 Tao Zhang,1 Lina Liu,2 Xiaolei Wang,1 Ping Wu,1 Zhigang Chen,1 Chao Ni,1 Junshu Zhang,1 Fuqiang Hu,4 Jian Huang1,31Cancer Institute, 2Department of Pharmacy, Second Affiliated Hospital (Binjiang Branch, 3Department of Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, 4College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, ChinaBackground and methods: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability, which leads to low systemic bioavailability. We have developed a novel nanoparticulate formulation of curcumin encapsulated in stearic acid-g-chitosan oligosaccharide (CSO-SA polymeric micelles to overcome these hurdles.Results: The synthesized CSO-SA copolymer was able to self-assemble to form nanoscale micelles in aqueous medium. The mean diameter of the curcumin-loaded CSO-SA micelles was 114.7 nm and their mean surface potential was 18.5 mV. Curcumin-loaded CSO-SA micelles showed excellent internalization ability that increased curcumin accumulation in cancer cells. Curcumin-loaded CSO-SA micelles also had potent antiproliferative effects on primary colorectal cancer cells in vitro, resulting in about 6-fold greater inhibition compared with cells treated with a solution containing an equivalent concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice, as confirmed by no change in body weight. Most importantly, curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44+/CD24+ cells (putative colorectal cancer stem cell markers both in vitro and in vivo.Conclusion: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for cancer therapy.Keywords: chitosan oligosaccharide, polymeric micelle, curcumin, drug delivery, colorectal cancer, cancer stem cells

  11. The Effect of Hydrophilic and Hydrophobic Structure of Amphiphilic Polymeric Micelles on Their Transportation in Rats.

    Deng, Feiyang; Yu, Chao; Zhang, Hua; Dai, Wenbing; He, Bing; Zheng, Ying; Wang, Xueqing; Zhang, Qiang


    In the previous study, we have clarified how the hydrophilic and hydrophobic structures of amphiphilic polymers impact the transport of their micelles (PEEP-PCL, PEG-PCL and PEG-DSPE micelles) in epithelial MDCK cells (Biomaterials 2013, 34: 6284-6298). In this study, we attempt to clarify the behavior of the three micelles in rats. Coumarin-6 loaded micelles were injected into different sections of intestine of rats and observed by confocal laser scanning microscope (CLSM) or orally administrated and conducted pharmacokinetic study. All of the three kinds of micelles were able to cross the intestinal epithelial cells and enter blood circulation. The PEEP-PCL micelles demonstrated the fastest distribution mainly in duodenum, while the PEGDSPE micelles showed the longest distribution with the highest proportion in ileum of the three. No significant difference was observed among the pharmacokinetic parameters of the three micelles. The results were consistent in the two analysis methods mentioned above, yet there were some differences between in vivo and in vitro results reported previously. It might be the distinction between the environments in MDCK model and intestine that led to the discrepancy. The hydrophobicity of nanoparticles could both enhance uptake and hinder the transport across the mucus. However, there was no intact mucus in MDCK model, which preferred hydrophobic nanoparticles. PEEP was the most hydrophilic material constructing the micelles in the study and its uptake would be increased in rats compared to that in MDCK model, while DSPE was more hydrophobic than the others and MDCK model would be more ideal for its uptake. Considering the inconsistency of the results in the two models, whether the methods researchers were generally using at present were reasonable needs further investigation.

  12. LPS-protein aggregation influences protein partitioning in aqueous two-phase micellar systems.

    Lopes, André Moreni; Santos-Ebinuma, Valéria de Carvalho; Novaes, Leticia Celia de Lencastre; Molino, João Vitor Dutra; Barbosa, Leandro Ramos Souza; Pessoa, Adalberto; Rangel-Yagui, Carlota de Oliveira


    Lipopolysaccharide endotoxins (LPS) are the most common pyrogenic substances in recombinant peptides and proteins purified from Gram-negative bacteria, such as Escherichia coli. In this respect, aqueous two-phase micellar systems (ATPMS) have already proven to be a good strategy to purify recombinant proteins of pharmaceutical interest and remove high LPS concentrations. In this paper, we review our recent experimental work in protein partitioning in Triton X-114 ATPMS altogether with some new results and show that LPS-protein aggregation can influence both protein and LPS partitioning. Green fluorescent protein (GFPuv) was employed as a model protein. The ATPMS technology proved to be effective for high loads of LPS removal into the micelle-rich phase (%REM(LPS) > 98 %) while GFPuv partitioned preferentially to the micelle-poor phase (K GFP(uv) system. Nonetheless, ATPMS can still be considered as an efficient strategy for high loads of LPS removal, but being aware that the excluded-volume partitioning theory available might overestimate partition coefficient values due to the presence of protein-LPS aggregation.

  13. Effective short-range Coulomb correction to model the aggregation behavior of ionic surfactants

    Burgos-Mármol, J. Javier; Solans, Conxita; Patti, Alessandro


    We present a short-range correction to the Coulomb potential to investigate the aggregation of amphiphilic molecules in aqueous solutions. The proposed modification allows to quantitatively reproduce the distribution of counterions above the critical micelle concentration (CMC) or, equivalently, the degree of ionization, α, of the micellar clusters. In particular, our theoretical framework has been applied to unveil the behavior of the cationic surfactant C24H49N2O2+ CH3SO4-, which offers a wide range of applications in the thriving and growing personal care market. A reliable and unambiguous estimation of α is essential to correctly understand many crucial features of the micellar solutions, such as their viscoelastic behavior and transport properties, in order to provide sound formulations for the above mentioned personal care solutions. We have validated our theory by performing extensive lattice Monte Carlo simulations, which show an excellent agreement with experimental observations. More specifically, our coarse-grained model is able to reproduce and predict the complex morphology of the micelles observed at equilibrium. Additionally, our simulation results disclose the existence of a transition from a monodisperse to a bidisperse size distribution of aggregates, unveiling the intriguing existence of a second CMC.

  14. pH-responsive layer-by-layer films of zwitterionic block copolymer micelles

    Demirel, Adem Levent; Yusan, Pelin; Tuncel, İrem; Bütün, Vural; Erel-Goktepe, İrem


    We report a strategy to incorporate micelles of poly[3-dimethyl (methacryloyloxyethyl) ammonium propane sulfonate]-block-poly[2-(diisopropylamino) ethyl methacrylate] (beta PDMA-b-PDPA) into electrostatic layer-by-layer (LbL) films. We obtained micelles with pH-responsive PDPA-cores and zwitterionic bPDMA-coronae at pH 8.5 through pH-induced self-assembly of bPDMA-b-PDPA in aqueous solution. To incorporate bPDMA-b-PDPA micelles into LbL films, we first obtained a net electrical charge on bPDM...

  15. Counterion condensation in ionic micelles as studied by a combined use of SANS and SAXS

    V K Aswal; P S Goyal; H Amenitsch; S Bernstorff


    We report a combined use of small-angle neutron scattering (SANS) and small-angle X-ray scattering (SAXS) to the study of counterion condensation in ionic micelles. Small-angle neutron and X-ray scattering measurements have been carried out on two surfactants cetyltrimethylammonium bromide (CTABr) and cetyltrimethylammonium chloride (CTACl), which are similar but having different counterions. SANS measurements show that CTABr surfactant forms much larger micelles than CTACl. This is explained in terms of higher condensation of Br0 counterions than Cl- counterions. SAXS data on these systems suggest that the Br- counterions are condensed around the micelles over smaller thickness than those of Cl- counterions.

  16. Dissipative particle dynamics simulation on paclitaxel loaded PEO-PPO-PEO block copolymer micelles.

    Wang, Zhigao; Jiang, Jie


    Self-assembly behavior of the polymer drug loading micelle PEO-PPO-PEO was studied using dissipative particle dynamics (DPD) simulation method with various simulation steps. The distributions of drugs in polymer carriers were also investigated with different drug feed ratios. Polymer carriers distributed on the surface of the spherical micelle, and drugs were almost encapsulated in the inner of the micelle. Our simulation work demonstrates that the DPD simulation is effective to study the drug loaded systems and can give useful guidance on the design and preparation of new drug carriers with tailored properties.

  17. Sphere-to-rod transition of triblock copolymer micelles at room temperature

    R Ganguly; V K Aswal; P A Hassan; I K Gopalakrishnan; J V Yakhmi


    A room temperature sphere-to-rod transition of the polyethylene oxide-polypropylene oxide-polyethylene oxide-based triblock copolymer, (PEO)20 (PPO)70 (PEO)20 micelles have been observed in aqueous medium under the influence of ethanol and sodium chloride. Addition of 5-10% ethanol induces a high temperature sphere-to-rod transition of the micelles, which is brought to room temperature upon addition of NaCl. The inference about the change in the shape of the micelles has been drawn from small-angle neutron scattering (SANS) and viscosity studies.

  18. Cation-π Interaction between the Aromatic Organic Counterion and DTAB Micelle in Mixed Solvents

    DENG,Dong-Shun(邓东顺); LI,Hao-Ran(李浩然); LIU,Di-Xia(刘迪霞); HAN,Shi-Jun(韩世钧)


    The cation-π interaction between the aromatic organic counterion potassium hydrogen phthalate (KHP) and DTAB micelle in aqueous mixture of EG was investigated, using the techniques of conductivity measurements, UV absorption spectrum and NMR spectrum. The conductivity and UV spectrum studies were with respect to the effect of KHP on DTAB and that of DTAB micelle on KHP, respectively. According to the chemical shift changes of the aromatic ring and the surfactant methylene protons, it can be assumed that KHP penetrated into DTAB micelle with its carboxylic group protruding out of the micellar surface. And the strength of the interaction became weaker with the content of EG in the mixed solvent increasing.

  19. Neutral Aggregation in Finite Length Genotype space

    Houchmandzadeh, Bahram


    The advent of modern genome sequencing techniques allows for a more stringent test of the neutrality hypothesis of Evolution, where all individuals have the same fitness. Using the individual based model of Wright and Fisher, we compute the amplitude of neutral aggregation in the genome space, i.e., the probability PL,$\\Theta$,M (k) of finding two individuals at genetic distance k for a genome of size L and mutation and migration number $\\Theta$ and M. In well mixed populations, we show that for $\\Theta$ $\\ll$ L, neutral aggregation is the dominant force and most individuals are found at short genetic distances from each other. For $\\Theta$ $\\sim$ L/2 on the contrary, individuals are randomly dispersed in genome space. For a geographically dispersed population, the controlling parameter is a combination of mutation and migration numbers. The theory we develop can be used to test the neutrality hypothesis in various ecological and evolutionary systems.

  20. Combined research effort on aggregate road materials

    Kuznetsova, Elena; Hoff, Inge; Willy Danielsen, Svein; Wigum, Børge Johannes; Fladvad, Marit; Rieksts, Karlis; Loranger, Benoit; Barbieri, Diego


    In European countries, the average aggregate consumption per capita is 5 tons per year (European Aggregates Association 2016), while the corresponding number in Norway is 11 tons (Neeb 2015). Due to the increased demand for sand and gravel for construction purposes, e.g. in road construction, the last decade has seen a significant trend towards the use of crushed rock aggregates. Neeb (2015) reports that half of the Norwegian aggregate production (sand, gravel and crushed rock) is used for road construction, and 33 % of the overall sold tonnage of crushed rock is exported. This resource has been more and more preferred over sand and gravel due to the significant technological development of its process and utilization phase. In Norway, the development and implementation of crushed aggregate technology has been the main approach to solve natural resource scarcity (Danielsen and Kuznetsova 2015). In order to reduce aggregates transportation, it is aimed to use local aggregates and aggregates processed from rock excavations, tunneling, road cuts, etc. One issue focused in this research is the influence from blasting and processing on the final quality of the crushed aggregates, specifically relating to the properties for road construction purposes. It is therefor crucial to plan utilization of available materials for use in different road layers following the same production line. New developments and improved availability of mobile crushing and screening equipment could produce more sustainable and profitable sources of good quality aggregate materials from small volume deposits in proximity to construction sites. One of the biggest challenges today to use these materials is that the pavement design manual sets rigid requirements for pavement layers. Four research projects are being conducted in Norway to improve the use of local materials for road construction. Four aspects are to be covered by the research: a) geological characteristics of the materials, their b

  1. Complement monitoring of Pluronic 127 gel and micelles

    Hamad, Islam; Hunter, A Christy; Moghimi, Seyed Moien


    Poloxamer 407 is a non-ionic polyethylene oxide (PEO)/polypropylene oxide (PPO) block copolymer, which exhibits reversible thermogelation properties. Poloxamer gel has attracted many applications for controlled release of therapeutic agents as well as in surgical interventions such as controlled...... vascular occlusion. We show that poloxamer gel can trigger the complement system, which is an integral part of innate immunity and its inadvertent activation can induce clinically significant anaphylaxis. Complement activation by the poloxamer gel is through the alternative pathway, but material...... transformations from gel to the solution state further incite complement through calcium-sensitive pathways, where a role for C1q and antibodies has been eliminated. Poloxamer addition to plasma/serum (at levels above its critical micelle concentration, cmc) induced formation of large and diffused structures...

  2. Structure-Property Relationships for Branched Worm-Like Micelles

    Beaucage, Gregory; Rai, Durgesh


    Micellar solutions can display a wide range of phase structure as a function of counter ion content, surfactant concentration, and the presence of ternary components. Under some conditions, common to consumer products, extended cylindrical structures that display persistence and other chain features of polymers are produced. These worm-like micelles (WLMs) can form branched structures that dynamically change under shear and even in quiescent conditions. The rheology of these branched WLMs is strongly dependent on migration of the branch points, and the dynamics of branch formation and removal. Persistence and other polymer-based descriptions are also of importance. We have recently developed a scattering model for branched polyolefins and other topologically complex materials that can quantify the branching density, branch length, branch functionality and the hyperbranch (branch-on-branch) content of polymers. This work is being extended to study branching in WLMs in work coupled with Ron Larson at UMich to predict rheological properties.

  3. Solute partitioning in aqueous surfactant assemblies: comparison of hydrophobic-hydrophilic interactions in micelles, alcohol-swollen micelles, microemulsions, and synthetic vesicles

    Russell, J.C.; Whitten, D.G.


    The structures of anionic assemblies including sodium lauryl sulfate (SLS) micelles, alcohol-swollen SLS micelles, microemulsions, and vesicles of a mixture of dipalmitoyllecithin and dicetyl phosphate are investigated by using the ground-state complexation of a hydrophilic quencher (methyl viologen) with several hydrophobic fluorescent probes, including surfactant stilbenes and 1,4-diphenylbutadiene. In SLS micelles this complexation can be decreased nearly an order of magnitude by addition of 1-heptanol, indicating that the structure of the micelle can be adjusted from the highly open structure of the pure micelle to a much more closed structure in which hydrophobic solubilizates can be sequestered from hydrophilic reagents bound to the surface. The fluorescence quenching process in anionic vesicles is strongly dependent on temperature; at low temperatures quenching occurs, while at higher temperatures addition of methyl viologen appears to increase the stilbene fluorescence, indicating that the dicationic quencher binds to the vesicle surface, increasing the order of the system. These results indicate that the degree of organization of surfactant systems can be adjusted by simple changes in composition. 33 references.

  4. Formation of Polyion Complex (PIC) Micelles and Vesicles with Anionic pH-Responsive Unimer Micelles and Cationic Diblock Copolymers in Water.

    Ohno, Sayaka; Ishihara, Kazuhiko; Yusa, Shin-Ichi


    A random copolymer (p(A/MaU)) of sodium 2-(acrylamido)-2-methylpropanesulfonate (AMPS) and sodium 11-methacrylamidoundecanate (MaU) was prepared via conventional radical polymerization, which formed a unimer micelle under acidic conditions due to intramolecular hydrophobic interactions between the pendant undecanoic acid groups. Under basic conditions, unimer micelles were opened up to an expanded chain conformation by electrostatic repulsion between the pendant sulfonate and undecanoate anions. A cationic diblock copolymer (P163M99) consisting of poly(3-(methacrylamido)propyl)trimethylammonium chloride (PMAPTAC) and hydrophilic polybetaine, 2-(methacryloyloxy)ethylphosphorylcholine (MPC), blocks was prepared via controlled radical polymerization. Mixing of p(A/MaU) and P163M99 in 0.1 M aqueous NaCl under acidic conditions resulted in the formation of spherical polyion complex (PIC) micelles and vesicles, depending on polymer concentration before mixing. Shapes of the PIC micelles and vesicles changed under basic conditions due to collapse of the charge balance between p(A/MaU) and P163M99. The PIC vesicles can incorporate nonionic hydrophilic guest molecules, and the PIC micelles and vesicles can accept hydrophobic guest molecules in the hydrophobic core formed from p(A/MaU).

  5. Novel aspects of platelet aggregation

    Roka-Moya Y. M.


    Full Text Available The platelet aggregation is an important process, which is critical for the hemostatic plug formation and thrombosis. Recent studies have shown that the platelet aggregation is more complex and dynamic than it was previously thought. There are several mechanisms that can initiate the platelet aggregation and each of them operates under specific conditions in vivo. At the same time, the influence of certain plasma proteins on this process should be considered. This review intends to summarize the recent data concerning the adhesive molecules and their receptors, which provide the platelet aggregation under different conditions.

  6. Fractal Aggregation Under Rotation

    WU Feng-Min; WU Li-Li; LU Hang-Jun; LI Qiao-Wen; YE Gao-Xiang


    By means of the Monte Carlo simulation, a fractal growth model is introduced to describe diffusion-limited aggregation (DLA) under rotation. Patterns which are different from the classical DLA model are observed and the fractal dimension of such clusters is calculated. It is found that the pattern of the clusters and their fractal dimension depend strongly on the rotation velocity of the diffusing particle. Our results indicate the transition from fractal to non-fractal behavior of growing cluster with increasing rotation velocity, i.e. for small enough angular velocity ω the fractal dimension decreases with increasing ω, but then, with increasing rotation velocity, the fractal dimension increases and the cluster becomes compact and tends to non-fractal.

  7. Fractal Aggregation Under Rotation

    WUFeng-Min; WULi-Li; LUHang-Jun; LIQiao-Wen; YEGao-Xiang


    By means of the Monte Carlo simulation, a fractal growth model is introduced to describe diffusion-limited aggregation (DLA) under rotation. Patterns which are different from the classical DLA model are observed and the fractal dimension of such clusters is calculated. It is found that the pattern of the clusters and their fractal dimension depend strongly on the rotation velocity of the diffusing particle. Our results indicate the transition from fractal to non-fractal behavior of growing cluster with increasing rotation velocity, i.e. for small enough angular velocity ω; thefractal dimension decreases with increasing ω;, but then, with increasing rotation velocity, the fractal dimension increases and the cluster becomes compact and tends to non-fractal.

  8. Platelet aggregation following trauma

    Windeløv, Nis A; Sørensen, Anne M; Perner, Anders


    We aimed to elucidate platelet function in trauma patients, as it is pivotal for hemostasis yet remains scarcely investigated in this population. We conducted a prospective observational study of platelet aggregation capacity in 213 adult trauma patients on admission to an emergency department (ED......). Inclusion criteria were trauma team activation and arterial cannula insertion on arrival. Blood samples were analyzed by multiple electrode aggregometry initiated by thrombin receptor agonist peptide 6 (TRAP) or collagen using a Multiplate device. Blood was sampled median 65 min after injury; median injury...... severity score (ISS) was 17; 14 (7%) patients received 10 or more units of red blood cells in the ED (massive transfusion); 24 (11%) patients died within 28 days of trauma: 17 due to cerebral injuries, four due to exsanguination, and three from other causes. No significant association was found between...

  9. Propagation of Tau Aggregates and Neurodegeneration.

    Goedert, Michel; Eisenberg, David S; Crowther, R Anthony


    A pathway from the natively unfolded microtubule-associated protein Tau to a highly structured amyloid fibril underlies human Tauopathies. This ordered assembly causes disease and represents the gain of toxic function. In recent years, evidence has accumulated to suggest that Tau inclusions form first in a small number of brain cells, from where they propagate to other regions, resulting in neurodegeneration and disease. Propagation of pathology is often called prion-like, which refers to the capacity of an assembled protein to induce the same abnormal conformation in a protein of the same kind, initiating a self-amplifying cascade. In addition, prion-like encompasses the release of protein aggregates from brain cells and their uptake by neighboring cells. In mice, the intracerebral injection of Tau inclusions induces the ordered assembly of monomeric Tau, followed by its spreading to distant brain regions. Conformational differences between Tau aggregates from transgenic mouse brain and in vitro assembled recombinant protein account for the greater seeding potency of brain aggregates. Short fibrils constitute the major species of seed-competent Tau in the brains of transgenic mice. The existence of multiple human Tauopathies with distinct fibril morphologies has led to the suggestion that different molecular conformers (or strains) of aggregated Tau exist.

  10. A two-component micelle with emergent pH responsiveness by mixing dilauroyl phosphocholine and deoxycholic acid and its delivery of proteins into the cytosol.

    Miyamoto, Noriko; Fujii, Shota; Mochizuki, Shinichi; Sakurai, Kazuo; Sakaguchi, Naoki; Koiwai, Kazunori


    Providing appropriate pH responsiveness for drug delivery nanoparticles is one of the major issues in developing a new generation of delivery systems. This paper reports that, when phosphocholine and a bile acid were mixed, the resultant two-component micelle gained pH responsiveness, while the individual components did not show any such responsiveness. The pH responsiveness was shown to be determined by the chemical structure, especially the positions and chirality of the OH groups, of the bile acid, and the sensitivity was determined by the alkyl chain length of the phosphocholine. The best combination for evading endocytosis was dilauroyl phosphocholine (DLPC) and deoxycholic acid (DA). Small-angle X-ray scattering revealed that the pH responsiveness was related to the change of surface hydrophobicity, namely, decreasing pH led to protonation of the carboxylic acid, resulting in aggregation of the preceding micelles. We assume that particles that become hydrophobic in this way can start interacting with the endocytotic bilayer, which eventually leads to rupture of the endocytotic vesicle. This mechanism is well supported by the finding that fluorescein-conjugated ovalbumin proteins were transported into the cytosol when they were co-administered with DLPC/DA. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Biodegradable polymeric micelle-encapsulated quercetin suppresses tumor growth and metastasis in both transgenic zebrafish and mouse models

    Wu, Qinjie; Deng, Senyi; Li, Ling; Sun, Lu; Yang, Xi; Liu, Xinyu; Liu, Lei; Qian, Zhiyong; Wei, Yuquan; Gong, Changyang


    Quercetin (Que) loaded polymeric micelles were prepared to obtain an aqueous formulation of Que with enhanced anti-tumor and anti-metastasis activities. A simple solid dispersion method was used, and the obtained Que micelles had a small particle size (about 31 nm), high drug loading, and high encapsulation efficiency. Que micelles showed improved cellular uptake, an enhanced apoptosis induction effect, and stronger inhibitory effects on proliferation, migration, and invasion of 4T1 cells than free Que. The enhanced in vitro antiangiogenesis effects of Que micelles were proved by the results that Que micelles significantly suppressed proliferation, migration, invasion, and tube formation of human umbilical vein endothelial cells (HUVECs). Subsequently, transgenic zebrafish models were employed to investigate anti-tumor and anti-metastasis effects of Que micelles, in which stronger inhibitory effects of Que micelles were observed on embryonic angiogenesis, tumor-induced angiogenesis, tumor growth, and tumor metastasis. Furthermore, in a subcutaneous 4T1 tumor model, Que micelles were more effective in suppressing tumor growth and spontaneous pulmonary metastasis, and prolonging the survival of tumor-bearing mice. Besides, immunohistochemical and immunofluorescent assays suggested that tumors in the Que micelle-treated group showed more apoptosis, fewer microvessels, and fewer proliferation-positive cells. In conclusion, Que micelles, which are synthesized as an aqueous formulation of Que, possess enhanced anti-tumor and anti-metastasis activity, which can serve as potential candidates for cancer therapy.

  12. Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment.

    Tonglairoum, Prasopchai; Woraphatphadung, Thisirak; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Akkaramongkolporn, Prasert; Sajomsang, Warayuth; Opanasopit, Praneet


    Clotrimazole (CZ)-loaded N-naphthyl-N,O-succinyl chitosan (NSCS) micelles have been developed as an alternative for oral candidiasis treatment. NSCS was synthesized by reductive N-amination and N,O-succinylation. CZ was incorporated into the micelles using various methods, including the dropping method, the dialysis method, and the O/W emulsion method. The size and morphology of the CZ-loaded micelles were characterized using dynamic light scattering measurements (DLS) and a transmission electron microscope (TEM), respectively. The drug entrapment efficiency, loading capacity, release characteristics, and antifungal activity against Candida albicans were also evaluated. The CZ-loaded micelles prepared using different methods differed in the size of micelles. The micelles ranged in size from 120 nm to 173 nm. The micelles prepared via the O/W emulsion method offered the highest percentage entrapment efficiency and loading capacity. The CZ released from the CZ-loaded micelles at much faster rate compared to CZ powder. The CZ-loaded NSCS micelles can significantly hinder the growth of Candida cells after contact. These CZ-loaded NSCS micelles offer great antifungal activity and might be further developed to be a promising candidate for oral candidiasis treatment.

  13. Use of Magnetic Folate-Dextran-Retinoic Acid Micelles for Dual Targeting of Doxorubicin in Breast Cancer

    J. Varshosaz


    Full Text Available Amphiphilic copolymer of folate-conjugated dextran/retinoic acid (FA/DEX-RA was self-assembled into micelles by direct dissolution method. Magnetic iron oxide nanoparticles (MNPs coated with oleic acid (OA were prepared by hydrothermal method and encapsulated within the micelles. Doxorubicin HCl was loaded in the magnetic micelles. The characteristics of the magnetic micelles were determined by Fourier transform infrared (FT-IR spectroscopy, thermogravimetric analysis (TGA, transmission electron microscopy (TEM, and vibrating sample magnetometer (VSM. The crystalline state of OA-coated MNPs and their heat capacity were analyzed by X-ray diffraction (XRD and differential scanning calorimetry (DSC methods, respectively. The iron content of magnetic micelles was determined using inductively coupled plasma optical emission spectrometry (ICP-OES. Bovine serum albumin (BSA was used to test the protein binding of magnetic micelles. The cytotoxicity of doxorubicin loaded magnetic micelles was studied on MCF-7 and MDA-MB-468 cells using MTT assay and their quantitative cellular uptake by fluorimetry method. TEM results showed the MNPs in the hydrophobic core of the micelles. TGA results confirmed the presence of OA and FA/DEX-RA copolymer on the surface of MNPs and micelles, respectively. The magnetic micelles showed no significant protein bonding and reduced the IC50 of the drug to about 10 times lower than the free drug.

  14. Cysteine modified and bile salt based micelles: preparation and application as an oral delivery system for paclitaxel.

    Xu, Wei; Fan, Xiaohui; Zhao, Yanli; Li, Lingbing


    The aim of the present study is to construct a cysteine modified polyion complex micelles made of Pluronic F127-chitosan (PF127-CS), Pluronic F127-cysteine (PF127-cysteine) and sodium cholate (NaC) and to evaluate the potential of the micelles as an oral drug delivery system for paclitaxel. Systematic studies on physicochemical properties including size distribution, zeta-potential and morphology were conducted to validate the formation of micelle structure. Compared with Pluronic micelles, drug-loading capacity of PF127-CS/PF127-cysteine/NaC micelles was increased from 3.35% to 12.77%. Both the critical micelle concentration and the stability test confirmed that the PF127-CS/PF127-cysteine/NaC micelles were more stable in aqueous solution than sodium cholate micelles. Pharmacokinetic study demonstrated that when oral administration the area under the plasma concentration-time curve (AUC0-∞) and the absolute bioavailability of paclitaxel-loaded micelles were five times greater than that of the paclitaxel solution. In general, PF127-CS/PF127-cysteine/NaC micelles were proven to be a potential oral drug delivery system for paclitaxel.

  15. Gold nanorod in reverse micelles: a fitting fusion to catapult lipase activity.

    Maiti, Subhabrata; Ghosh, Moumita; Das, Prasanta Kumar


    Lipase solubilized within gold nanorod doped CTAB reverse micelles exhibited remarkable improvement in its activity mainly due to the enhanced interfacial domain of newly developed self-assembled nanocomposites.


    Pan He; Chang-wen Zhao; Chun-sheng Xiao; Zhao-hui Tang; Xue-si Chen


    Polyion complex (PIC) micelles were spontaneously formed in aqueous solutions through electrostatic interaction between two oppositely charged block copolymers,poly(N-isopropylacrylamide)-b-poly(L-glutamic acid) and poly(N-isopropylacrylamide)-b-poly(L-lysine).Their controlled synthesis was achieved via the ring opening polymerization of N-carboxyanhydrides (NCA),ε-benzyloxycarbonyl-L-lysine (Lys(Z)-NCA) or γ-benzyl-L-glutamate (BLG-NCA) with amino-terminated poly(N-isopropylacrylamide) macroinitiator and the subsequent deprotection reaction.The formation of PIC micelles was confirmed by dynamic light scattering and transmission electron microscopy.Turbidimetric characterization suggested that the formed PIC micelles had a concentration-dependent thermosensitivity and their phase transition behaviors could be easily adjusted either by the block length of coplymers or the concentration of micelles.

  17. Effect of calcium chelators on physical changes in casein micelles in concentrated micellar casein solutions

    Kort, de E.J.P.; Minor, M.; Snoeren, T.H.M.; Hooijdonk, van A.C.M.; Linden, van der E.


    The effect of calcium chelators on physical changes of casein micelles in concentrated micellar casein solutions was investigated by measuring calcium-ion activity, viscosity and turbidity, and performing ultracentrifugation. The highest viscosities were measured on addition of sodium

  18. CD and 31P NMR studies of tachykinin and MSH neuropeptides in SDS and DPC micelles

    Schneider, Sydney C.; Brown, Taylor C.; Gonzalez, Javier D.; Levonyak, Nicholas S.; Rush, Lydia A.; Cremeens, Matthew E.


    Secondary structural characteristics of substance P (SP), neurokinin A (NKA), neurokinin B (NKB), α-melanocyte stimulating hormone peptide (α-MSH), γ1-MSH, γ2-MSH, and melittin were evaluated with circular dichroism in phosphite buffer, DPC micelles, and SDS micelles. CD spectral properties of γ1-MSH and γ2-MSH as well as 31P NMR of DPC micelles with all the peptides are reported for the first time. Although, a trend in the neuropeptide/micelle CD data appears to show increased α-helix content for the tachykinin peptides (SP, NKA, NKB) and increased β-sheet content for the MSH peptides (α-MSH, γ1-MSH, γ2-MSH) with increasing peptide charge, the lack of perturbed 31P NMR signals for all neuropeptides could suggest that the reported antimicrobial activity of SP and α-MSH might not be related to a membrane disruption mode of action.

  19. Exploring Polymeric Micelles for Improved Delivery of Anticancer Agents: Recent Developments in Preclinical Studies

    Wei Fan


    Full Text Available As versatile drug delivery systems, polymeric micelles have demonstrated particular strength in solubilizing hydrophobic anticancer drugs while eliminating the use of toxic organic solvents and surfactants. However, the true promise of polymeric micelles as drug carriers for cancer therapy resides in their potential ability to preferentially elevate drug exposure in the tumor and achieve enhanced anticancer efficacy, which still remains to be fully exploited. Here, we review various micellar constructs that exhibit the enhanced permeation and retention effect in the tumor, the targeting ligands that potentiate the anticancer efficacy of micellar drugs, and the polyplex micelle systems suitable for the delivery of plasmid DNA and small interference RNA. Together, these preclinical studies in animal models help us further explore polymeric micelles as emerging drug carriers for targeted cancer therapy.

  20. Effect of substitution on aniline in inducing growth of anionic micelles

    Gunjan Garg; V K Aswal; S K Kulshreshtha; P A Hassan


    Small-angle neutron scattering (SANS) measurements were carried out on sodium dodecyl sulfate (SDS) micelles in the presence of three different hydrophobic salts, i.e. aniline hydrochloride, -toluidine hydrochloride and -toluidine hydrochloride. All these salts induce a uniaxial growth of micelles to form prolate ellipsoidal structures. A progressive decrease in the surface charge of the micelles was observed with the addition of salts followed by a rapid growth of the micelles. The presence of a methyl substitution at the ortho position of aniline does not alter the growth behavior significantly. However, when the substitution is at meta position micellar growth is favored at lower salt concentration than that is observed for aniline. This can be explained in terms of the difference in the chemical environments of the substituents at the ortho and meta positions.