Structure formation in binary mixtures of lipids and detergents: self-assembly and vesicle division.

PubMed

Noguchi, Hiroshi

2013-01-14

Self-assembly dynamics in binary surfactant mixtures and structure changes of lipid vesicles induced by detergent solution are studied using coarse-grained molecular simulations. Disk-shaped micelles, the bicelles, are stabilized by detergents surrounding the rim of a bilayer disk of lipids. The self-assembled bicelles are considerably smaller than bicelles formed from vesicle rupture, and their size is determined by the concentrations of lipids and detergents and the interactions between the two species. The detergent-adsorption induces spontaneous curvature of the vesicle bilayer and results in vesicle division into two vesicles or vesicle rupture into worm-like micelles. The division occurs mainly via the inverse pathway of the modified stalk model. For large spontaneous curvature of the monolayers of the detergents, a pore is often opened, thereby leading to vesicle division or worm-like micelle formation.

Activation energy and entropy for viscosity of wormlike micelle solutions.

PubMed

Chandler, H D

2013-11-01

The viscosities of two surfactant solutions which form wormlike micelles (WLMs) were studied over a range of temperatures and strain rates. WLM solutions appear to differ from many other shear thinning systems in that, as the shear rate increases, stress-shear rate curves tend to converge with temperature rather than diverge and this can sometimes lead to higher temperature curves crossing those at lower. Behaviour was analysed in terms of activation kinetics. It is suggested that two mechanisms are involved: Newtonian flow, following an Arrhenius law superimposed on a non-Newtonian flow described by a stress assisted kinetic law, this being a more general form of the Arrhenius law. Anomalous flow is introduced into the kinetic equation via a stress dependent activation entropy term. Copyright © 2013 Elsevier Inc. All rights reserved.

Influence of system size and solvent flow on the distribution of wormlike micelles in a contraction-expansion geometry

NASA Astrophysics Data System (ADS)

Stukan, M. R.; Boek, E. S.; Padding, J. T.; Crawshaw, J. P.

2008-05-01

Viscoelastic wormlike micelles are formed by surfactants assembling into elongated cylindrical structures. These structures respond to flow by aligning, breaking and reforming. Their response to the complex flow fields encountered in porous media is particularly rich. Here we use a realistic mesoscopic Brownian Dynamics model to investigate the flow of a viscoelastic surfactant (VES) fluid through individual pores idealized as a step expansion-contraction of size around one micron. In a previous study, we assumed the flow field to be Newtonian. Here we extend the work to include the non-Newtonian flow field previously obtained by experiment. The size of the simulations is also increased so that the pore is much larger than the radius of gyration of the micelles. For the non-Newtonian flow field at the higher flow rates in relatively large pores, the density of the micelles becomes markedly non-uniform. In this case, we find that the density in the large, slowly moving entry corner regions is substantially increased.

In vivo evaluation of folate decorated cross-linked micelles for the delivery of platinum anticancer drugs.

PubMed

Eliezar, Jeaniffer; Scarano, Wei; Boase, Nathan R B; Thurecht, Kristofer J; Stenzel, Martina H

2015-02-09

The biodistribution of micelles with and without folic acid targeting ligands were studied using a block copolymer consisting of acrylic acid (AA) and polyethylene glycol methyl ether acrylate (PEGMEA) blocks. The polymers were prepared using RAFT polymerization in the presence of a folic acid functionalized RAFT agent. Oxoplatin was conjugated onto the acrylic acid block to form amphiphilic polymers which, when diluted in water, formed stable micelles. In order to probe the in vivo stability, a selection of micelles were cross-linked using 1,8-diamino octane. The sizes of the micelles used in this study range between 75 and 200 nm, with both spherical and worm-like conformation. The effects of cross-linking, folate conjugation and different conformation on the biodistribution were studied in female nude mice (BALB/c) following intravenous injection into the tail vein. Using optical imaging to monitor the fluorophore-labeled polymer, the in vivo biodistribution of the micelles was monitored over a 48 h time-course after which the organs were removed and evaluated ex vivo. These experiments showed that both cross-linking and conjugation with folic acid led to increased fluorescence intensities in the organs, especially in the liver and kidneys, while micelles that are not conjugated with folate and not cross-linked are cleared rapidly from the body. Higher accumulation in the spleen, liver, and kidneys was also observed for micelles with worm-like shapes compared to the spherical micelles. While the various factors of cross-linking, micelle shape, and conjugation with folic acid all contribute separately to prolong the circulation time of the micelle, optimization of these parameters for drug delivery devices could potentially overcome adverse effects such as liver and kidney toxicity.

Nanorod Mobility within Entangled Wormlike Micelle Solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Jonghun; Grein-Iankovski, Aline; Narayanan, Suresh

In the semi-dilute regime, wormlike micelles form an isotropic entangled microstructure that is similar to that of an entangled polymer solution with a characteristic, nanometer-scale entanglement mesh size. We report a combined x-ray photon correlation spectroscopy (XPCS) and rheology study to investigate the translational dynamics of gold nanorods in semi-dilute solutions of entangled wormlike micelles formed by the surfactant cetylpyridinium chloride (CPyCl) and the counter-ion sodium salicylate (NaSal). The CPyCl concentration is varied to tune the entanglement mesh size over a range that spans from approximately equal to the nanorod diameter to larger than the nanorod length. The NaSal concentrationmore » is varied along with the CPyCl concentration so that the solutions have the maximum viscosity for given CPyCl concentration. On short time scales the nanorods are localized on a length scale matching that expected from the high-frequency elastic modulus of the solutions as long as the mesh size is smaller than the rod length. On longer time scales, the nanorods undergo free diffusion. At the highest CPyCl concentrations, the nanorod diffusivity approaches the value expected based on the macroscopic viscosity of the solutions, but it increases with decreasing CPyCl concentration more rapidly than expected from the macroscopic viscosity. A recent model by Cai et al. [Cai, L.-H.; Panyukov, S.; Rubinstein, M. Macromolecules 2015, 48, 847-862.] for nanoparticle “hopping” diffusion in entangled polymer solutions accounts quantitatively for this enhanced diffusivity.« less

Nanorod Mobility within Entangled Wormlike Micelle Solutions

DOE PAGES

Lee, Jonghun; Grein-Iankovski, Aline; Narayanan, Suresh; ...

2016-12-20

In the semi-dilute regime, wormlike micelles form an isotropic entangled microstructure that is similar to that of an entangled polymer solution with a characteristic, nanometer-scale entanglement mesh size. We report a combined x-ray photon correlation spectroscopy (XPCS) and rheology study to investigate the translational dynamics of gold nanorods in semi-dilute solutions of entangled wormlike micelles formed by the surfactant cetylpyridinium chloride (CPyCl) and the counter-ion sodium salicylate (NaSal). The CPyCl concentration is varied to tune the entanglement mesh size over a range that spans from approximately equal to the nanorod diameter to larger than the nanorod length. The NaSal concentrationmore » is varied along with the CPyCl concentration so that the solutions have the maximum viscosity for given CPyCl concentration. On short time scales the nanorods are localized on a length scale matching that expected from the high-frequency elastic modulus of the solutions as long as the mesh size is smaller than the rod length. On longer time scales, the nanorods undergo free diffusion. At the highest CPyCl concentrations, the nanorod diffusivity approaches the value expected based on the macroscopic viscosity of the solutions, but it increases with decreasing CPyCl concentration more rapidly than expected from the macroscopic viscosity. A recent model by Cai et al. [Cai, L.-H.; Panyukov, S.; Rubinstein, M. Macromolecules 2015, 48, 847-862.] for nanoparticle “hopping” diffusion in entangled polymer solutions accounts quantitatively for this enhanced diffusivity.« less

Smart worm-like micelles responsive to CO2/N2 and light dual stimuli.

PubMed

Jiang, Jianzhong; Wang, Guozheng; Ma, Yuxuan; Cui, Zhenggang; Binks, Bernard P

2017-04-12

CO 2 /N 2 and light dual stimuli-responsive worm-like micelles (WLMs) were obtained by addition of a relatively small amount of a switchable surfactant, 4-butyl-4'-(4-N,N-dimethylhexyloxy-amine) azobenzene bicarbonate (AZO-B6-CO 2 ), sensitive to the same triggers to a binary aqueous solution of cetyltrimethylammonium bromide (CTAB) and sodium salicylate (NaSal).

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

NASA Astrophysics Data System (ADS)

Noguchi, Hiroshi

2013-02-01

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.

Smart wormlike micelles.

PubMed

Chu, Zonglin; Dreiss, Cécile A; Feng, Yujun

2013-09-07

A major scientific challenge of the past decade pertaining to the field of soft matter has been to craft 'adaptable' materials, inspired by nature, which can dynamically alter their structure and functionality on demand, in response to triggers produced by environmental changes. Amongst these, 'smart' surfactant wormlike micelles, responsive to external stimuli, are a particularly recent area of development, yet highly promising, given the versatility of the materials but simplicity of the design-relying on small amphiphilic molecules and their spontaneous self-assembly. The switching 'on' and 'off' of the micellar assembly structures has been reported using electrical, optical, thermal or pH triggers and is now envisaged for multiple stimuli. The structural changes, in turn, can induce major variations in the macroscopic characteristics, affecting properties such as viscosity and elasticity and sometimes even leading to a spontaneous and effective 'sol-gel' transition. These original smart materials based on wormlike micelles have been successfully used in the oil industry, and offer a significant potential in a wide range of other technological applications, including biomedicine, cleaning processes, drag reduction, template synthesis, to name but a few. This review will report results in this field published over the last few years, describe the potential and practical applications of stimuli-responsive wormlike micelles and point out future challenges.

Single-coil properties and concentration effects for polyelectrolyte-like wormlike micelles: a Monte Carlo study

NASA Astrophysics Data System (ADS)

Cannavacciuolo, Luigi; Skov Pedersen, Jan; Schurtenberger, Peter

2002-03-01

Results of an extensive Monte Carlo (MC) study on both single and many semiflexible charged chains with excluded volume (EV) are summarized. The model employed has been tailored to mimic wormlike micelles in solution. Simulations have been performed at different ionic strengths of added salt, charge densities, chain lengths and volume fractions Φ, covering the dilute to concentrated regime. At infinite dilution the scattering functions can be fitted by the same fitting functions as for uncharged semiflexible chains with EV, provided that an electrostatic contribution bel is added to the bare Kuhn length. The scaling of bel is found to be more complex than the Odijk-Skolnick-Fixman predictions, and qualitatively compatible with more recent variational calculations. Universality in the scaling of the radius of gyration is found if all lengths are rescaled by the total Kuhn length. At finite concentrations, the simple model used is able to reproduce the structural peak in the scattering function S(q) observed in many experiments, as well as other properties of polyelectrolytes (PELs) in solution. Universal behaviour of the forward scattering S(0) is established after a rescaling of Φ. MC data are found to be in very good agreement with experimental scattering measurements with equilibrium PELs, which are giant wormlike micelles formed in mixtures of nonionic and ionic surfactants in dilute aqueous solution, with added salt.

Drug Combination Synergy in Worm-like Polymeric Micelles Improves Treatment Outcome for Small Cell and Non-Small Cell Lung Cancer.

PubMed

Wan, Xiaomeng; Min, Yuanzeng; Bludau, Herdis; Keith, Andrew; Sheiko, Sergei S; Jordan, Rainer; Wang, Andrew Z; Sokolsky-Papkov, Marina; Kabanov, Alexander V

2018-03-27

Nanoparticle-based systems for concurrent delivery of multiple drugs can improve outcomes of cancer treatments, but face challenges because of differential solubility and fairly low threshold for incorporation of many drugs. Here we demonstrate that this approach can be used to greatly improve the treatment outcomes of etoposide (ETO) and platinum drug combination ("EP/PE") therapy that is the backbone for treatment of prevalent and deadly small cell lung cancer (SCLC). A polymeric micelle system based on amphiphilic block copolymer poly(2-oxazoline)s (POx) poly(2-methyl-2-oxazoline- block-2-butyl-2-oxazoline- block-2-methyl-2-oxazoline) (P(MeOx- b-BuOx- b-MeOx) is used along with an alkylated cisplatin prodrug to enable co-formulation of EP/PE in a single high-capacity vehicle. A broad range of drug mixing ratios and exceptionally high two-drug loading of over 50% wt. drug in dispersed phase is demonstrated. The highly loaded POx micelles have worm-like morphology, unprecedented for drug loaded polymeric micelles reported so far, which usually form spheres upon drug loading. The drugs co-loading in the micelles result in a slowed-down release, improved pharmacokinetics, and increased tumor distribution of both drugs. A superior antitumor activity of co-loaded EP/PE drug micelles compared to single drug micelles or their combination as well as free drug combination was demonstrated using several animal models of SCLC and non-small cell lung cancer.

Fluctuations of wormlike micelle fluids in capillary flow

NASA Astrophysics Data System (ADS)

Salipante, Paul; Meek, Stephen; Hudson, Steven; Polymers; Complex Fluids Group Team

2017-11-01

We investigate the effect of entrance geometry on the flow stability of wormlike micelles solutions in capillary flow. These solutions exhibit strong shear thinning behavior resulting from micelle breakage and have been observed to undergo large flow rate fluctuations. We investigate these fluctuations using simultaneous measurements of flow rate and pressure drop across a capillary, and we adjust entrance geometry. With a tapered constriction, we observe large persistent fluctuations above a critical flow rate, characterized by rapid decreases in the pressure drop with corresponding increase in flow rate followed by a period of recovery where pressure increases and flow rate decreases. Flow field observations in the tapered entrance show large flow circulations. An abrupt contraction produces smaller transient fluidized jets forming upstream of the constriction and the magnitude of the fluctuations are significantly diminished. The effect of fluid properties is studied by comparing the magnitude and timescales of the fluctuations for surfactant systems with different relaxation times. The onset of fluctuations is compared to a criterion for the onset of elastic instabilities and the magnitude is compared to estimates for changes in channel resistance. NIST on a Chip.

The elasticity of soap bubbles containing wormlike micelles.

PubMed

Sabadini, Edvaldo; Ungarato, Rafael F S; Miranda, Paulo B

2014-01-28

Slow-motion imaging of the rupture of soap bubbles generally shows the edges of liquid films retracting at a constant speed (known as the Taylor-Culick velocity). Here we investigate soap bubbles formed from simple solutions of a cationic surfactant (cetyltrimethylammonium bromide - CTAB) and sodium salicylate. The interaction of salicylate ions with CTAB leads to the formation of wormlike micelles (WLM), which yield a viscoelastic behavior to the liquid film of the bubble. We demonstrate that these elastic bubbles collapse at a velocity up to 30 times higher than the Taylor-Culick limit, which has never been surpassed. This is because during the bubble inflation, the entangled WLM chains stretch, storing elastic energy. This extra energy is then released during the rupture of the bubble, yielding an additional driving force for film retraction (besides surface tension). This new mechanism for the bursting of elastic bubbles may have important implications to the breakup of viscoelastic sprays in industrial applications.

A pH-responsive wormlike micellar system of a noncovalent interaction-based surfactant with a tunable molecular structure.

PubMed

Kang, Wanli; Wang, Pengxiang; Fan, Haiming; Yang, Hongbin; Dai, Caili; Yin, Xia; Zhao, Yilu; Guo, Shujun

2017-02-08

Responsive wormlike micelles are very useful in a number of applications, whereas it is still challenging to create dramatic viscosity changes in wormlike micellar systems. Here we developed a pH-responsive wormlike micellar system based on a noncovalent constructed surfactant, which is formed by the complexation of N-erucamidopropyl-N,N-dimethylamine (UC 22 AMPM) and citric acid at the molar ratio of 3 : 1 (EACA). The phase behavior, aggregate microstructure and viscoelasticity of EACA solutions were investigated by macroscopic appearance observation, rheological and cryo-TEM measurements. It was found that the phase behavior of EACA solutions undergoes transition from transparent viscoelastic fluids to opalescent solutions and then phase separation with white floaters upon increasing the pH. Upon increasing the pH from 2.03 to 6.17, the viscosity of wormlike micelles in the transparent solutions continuously increased and reached ∼683 000 mPa s at pH 6.17. As the pH was adjusted to 7.31, the opalescent solution shows a water-like flowing behaviour and the η 0 rapidly declines to ∼1 mPa s. Thus, dramatic viscosity changes of about 6 magnitudes can be triggered by varying the pH values without any deterioration of the EACA system. This drastic variation in rheological behavior is attributed to the pH dependent interaction between UC 22 AMPM and citric acid. Furthermore, the dependence on concentration and temperature of the rheological behavior of EACA solutions was also studied to assist in obtaining the desired pH-responsive viscosity changes.

Viscoelastic diamine surfactant for stable carbon dioxide/water foams over a wide range in salinity and temperature.

PubMed

Elhag, Amro S; Da, Chang; Chen, Yunshen; Mukherjee, Nayan; Noguera, Jose A; Alzobaidi, Shehab; Reddy, Prathima P; AlSumaiti, Ali M; Hirasaki, George J; Biswal, Sibani L; Nguyen, Quoc P; Johnston, Keith P

2018-07-15

The viscosity and stability of CO 2 /water foams at elevated temperature can be increased significantly with highly viscoelastic aqueous lamellae. The slow thinning of these viscoelastic lamellae leads to greater foam stability upon slowing down Ostwald ripening and coalescence. In the aqueous phase, the viscoelasticity may be increased by increasing the surfactant tail length to form more entangled micelles even at high temperatures and salinity. Systematic measurements of the steady state shear viscosity of aqueous solutions of the diamine surfactant (C 16-18 N(CH 3 )C 3 N(CH 3 ) 2 ) were conducted at varying surfactant concentrations and salinity to determine the parameters for formation of entangled wormlike micelles. The apparent viscosity and stability of CO 2 /water foams were compared for systems with viscoelastic entangled micellar aqueous phases relative to those with much less viscous spherical micelles. We demonstrated for the first time stable CO 2 /water foams at temperatures up to 120 °C and CO 2 volumetric fractions up to 0.98 with a single diamine surfactant, C 16-18 N(CH 3 )C 3 N(CH 3 ) 2 . The foam stability was increased by increasing the packing parameter of the surfactant with a long tail and methyl substitution on the amine to form entangled viscoelastic wormlike micelles in the aqueous phase. The foam was more viscous and stable compared to foams with spherical micelles in the aqueous lamellae as seen with C 12-14 N(EO) 2 and C 16-18 N(EO)C 3 N(EO) 2 . Copyright © 2018. Published by Elsevier Inc.

Sol-gel transition behavior of aqueous peptide-amphiphile (C16-W3K) solutions: effects of alkyl-tail length, mechanical shear, temperature, and salt

NASA Astrophysics Data System (ADS)

Yamamoto, Masashi; Otsuka, Takahiro; Orimo, Yoshinori; Maeda, Tomoki; Hotta, Atsushi

Peptide amphiphiles (PA) possess nanoscale micelle structures and excellent biocompatibility. In aqueous PA solution, PA molecules can self-assemble through various configurations into spherical and wormlike micelles, which can occasionally form hydrogels. C16-W3K is one of the unique PA, whose micelle configurations can transfer from spherical to wormlike structures in its aqueous solution over time, while the wormlike micelles could also lead to gelation. In our recent research, the effects of the length of the hydrophobic alkyl tail and other external factors of C16-W3K on the gelation behavior of the C16-W3K solution have been discussed. It has been revealed that longer alkyl-tails could facilitate the gelation of the C16-W3K solution, and that the external stimuli, such as mechanical shear and heat, could promote faster gelation of the C16-W3K solution. It was also found that salt could adjust the pH of the C16-W3K solution, having profound influence on the gelation behavior of the C16-W3K solution. In fact, the gelation of the C16-W3K with a higher storage modulus could be obtained from relatively acidic solutions, while the gelation of the C16-W3K solution was firmly suppressed in highly basic solutions. This work was supported by a Grant-in-Aid for Scientific Research (A) (No. 15H02298 to A.H.) and a Grant-in-Aid for Research Activity Start-up (No.15H06586 to T.M.) from JSPS: KAKENHI.

Growth of wormlike micelles in nonionic surfactant solutions: Quantitative theory vs. experiment.

PubMed

Danov, Krassimir D; Kralchevsky, Peter A; Stoyanov, Simeon D; Cook, Joanne L; Stott, Ian P; Pelan, Eddie G

2018-06-01

Despite the considerable advances of molecular-thermodynamic theory of micelle growth, agreement between theory and experiment has been achieved only in isolated cases. A general theory that can provide self-consistent quantitative description of the growth of wormlike micelles in mixed surfactant solutions, including the experimentally observed high peaks in viscosity and aggregation number, is still missing. As a step toward the creation of such theory, here we consider the simplest system - nonionic wormlike surfactant micelles from polyoxyethylene alkyl ethers, C i E j . Our goal is to construct a molecular-thermodynamic model that is in agreement with the available experimental data. For this goal, we systematized data for the micelle mean mass aggregation number, from which the micelle growth parameter was determined at various temperatures. None of the available models can give a quantitative description of these data. We constructed a new model, which is based on theoretical expressions for the interfacial-tension, headgroup-steric and chain-conformation components of micelle free energy, along with appropriate expressions for the parameters of the model, including their temperature and curvature dependencies. Special attention was paid to the surfactant chain-conformation free energy, for which a new more general formula was derived. As a result, relatively simple theoretical expressions are obtained. All parameters that enter these expressions are known, which facilitates the theoretical modeling of micelle growth for various nonionic surfactants in excellent agreement with the experiment. The constructed model can serve as a basis that can be further upgraded to obtain quantitative description of micelle growth in more complicated systems, including binary and ternary mixtures of nonionic, ionic and zwitterionic surfactants, which determines the viscosity and stability of various formulations in personal-care and house-hold detergency. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Entropic effects, shape, and size of mixed micelles formed by copolymers with complex architectures

NASA Astrophysics Data System (ADS)

Kalogirou, Andreas; Gergidis, Leonidas N.; Moultos, Othonas; Vlahos, Costas

2015-11-01

The entropic effects in the comicellization behavior of amphiphilic A B copolymers differing in the chain size of solvophilic A parts were studied by means of molecular dynamics simulations. In particular, mixtures of miktoarm star copolymers differing in the molecular weight of solvophilic arms were investigated. We found that the critical micelle concentration values show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This can be attributed to the effective interactions between copolymers originated from the arm size asymmetry. The effective interactions induce a very small decrease in the aggregation number of preferential micelles triggering the nonrandom mixing between the solvophilic moieties in the corona. Additionally, in order to specify how the chain architecture affects the size distribution and the shape of mixed micelles we studied star-shaped, H-shaped, and homo-linked-rings-linear mixtures. In the first case the individual constituents form micelles with preferential and wide aggregation numbers and in the latter case the individual constituents form wormlike and spherical micelles.

Entropic effects, shape, and size of mixed micelles formed by copolymers with complex architectures.

PubMed

Kalogirou, Andreas; Gergidis, Leonidas N; Moultos, Othonas; Vlahos, Costas

2015-11-01

The entropic effects in the comicellization behavior of amphiphilic AB copolymers differing in the chain size of solvophilic A parts were studied by means of molecular dynamics simulations. In particular, mixtures of miktoarm star copolymers differing in the molecular weight of solvophilic arms were investigated. We found that the critical micelle concentration values show a positive deviation from the analytical predictions of the molecular theory of comicellization for chemically identical copolymers. This can be attributed to the effective interactions between copolymers originated from the arm size asymmetry. The effective interactions induce a very small decrease in the aggregation number of preferential micelles triggering the nonrandom mixing between the solvophilic moieties in the corona. Additionally, in order to specify how the chain architecture affects the size distribution and the shape of mixed micelles we studied star-shaped, H-shaped, and homo-linked-rings-linear mixtures. In the first case the individual constituents form micelles with preferential and wide aggregation numbers and in the latter case the individual constituents form wormlike and spherical micelles.

Rheology of wormlike micellar fluids from Brownian and molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Padding, J. T.; Boek, E. S.; Briels, W. J.

2005-11-01

There is a great need for understanding the link between the detailed chemistry of surfactants, forming wormlike micelles, and their macroscopic rheological properties. In this paper we show how this link may be explored through particle simulations. First we review an existing bead-spring model. We find that shear flow enhances the formation of rings at the expense of linear chains. The shear viscosity of this model is dominated by solvent contributions, however, and the link with the chemistry of the surfactants is missing. We introduce a more realistic Brownian dynamics model, the parameters of which are measured from atomistic molecular dynamics simulations.

Novel Hydrogels from Telechelic Polymers

NASA Astrophysics Data System (ADS)

Taribagil, Rajiv R.

The last two decades have seen telechelic polymers support an increasing number of applications as stabilizers and flow modifiers in fields as varied as pharmaceutics, paints and oil recovery. Mainly consisting of a long hydrophilic block end-capped with hydrophobic blocks, these polymers form gels at modest concentrations, comprising hydrophobic junctions with hydrophilic blocks bridging these junctions. This thesis examines two different types of telechelic polymer hydrogels: concentrated dispersions of telechelic triblock copolymers and dilute solutions of wormlike micelles cross-linked by hydrophobically end-capped polymers. Aqueous gels of telechelic poly(ethylene oxide) (PEO)-based triblock polymers, with homo and hetero combinations of 1,2-polybutadiene (PB) and poly(perfluoropropylene oxide) (PFPO) as hydrophobic end-blocks, were investigated using a combination of cryogenic scanning electron microscopy and small-angle neutron scattering. The PB-b-PEO-b-PB copolymers formed networks of spherical micelles at all concentrations as expected, albeit with significant spatial heterogeneity that diminished with increasing concentration. The PFPO-b-PEO-b-PFPO copolymers also formed networks by aggregation of the end-blocks, but the PFPO blocks tended to adopt disk-like or even sheet-like structures. This is attributed to the extremely high interfacial tension of PFPO with water and is consistent with the "super-strong" segregation regime behavior. The heterotelechelic PB-b-PEO- b-PFPO terpolymers adopted a quite different structure, namely an intricate bicontinuous open-cell foam, with cells on the order of 500 nm in size and cell walls composed of PFPO disks embedded in PB sheets. These various network structures illustrate the potential of using end-block chemistry to manipulate both the morphology and the physical properties of polymer gels. Dilute aqueous solutions containing 1 wt% cetyltrimethylammonium tosylate, a surfactant well recognized to form wormlike micelles, and low concentrations of hydrophobically end-capped poly(ethylene oxide), were investigated using dynamic mechanical spectroscopy and small-angle neutron scattering. The detailed examination shows that addition of as little as 0.1 wt% of the polymer to the dilute wormlike micelle solution leads to a massive enhancement in its viscoelastic response. This phenomenon raises the possibility of significantly reducing the amount of additive required to achieve a desired rheological profile, with concomitant advantages in both cost and environmental impact.

Phospholipid Nonwoven Electrospun Membranes

NASA Astrophysics Data System (ADS)

McKee, Matthew G.; Layman, John M.; Cashion, Matthew P.; Long, Timothy E.

2006-01-01

Nonwoven fibrous membranes were formed from electrospinning lecithin solutions in a single processing step. As the concentration of lecithin increased, the micellar morphology evolved from spherical to cylindrical, and at higher concentrations the cylindrical micelles overlapped and entangled in a fashion similar to polymers in semi-dilute or concentrated solutions. At concentrations above the onset of entanglements of the wormlike micelles, electrospun fibers were fabricated with diameters on the order of 1 to 5 micrometers. The electrospun phospholipid fibers offer the potential for direct fabrication of biologically based, high-surface-area membranes without the use of multiple synthetic steps, complicated electrospinning designs, or postprocessing surface treatments.

Instabilities in wormlike micelle systems. From shear-banding to elastic turbulence.

PubMed

Fardin, M-A; Lerouge, S

2012-09-01

Shear-banding is ubiquitous in complex fluids. It is related to the organization of the flow into macroscopic bands bearing different viscosities and local shear rates and stacked along the velocity gradient direction. This flow-induced transition towards a heterogeneous flow state has been reported in a variety of systems, including wormlike micellar solutions, telechelic polymers, emulsions, clay suspensions, colloidal gels, star polymers, granular materials, or foams. In the past twenty years, shear-banding flows have been probed by various techniques, such as rheometry, velocimetry and flow birefringence. In wormlike micelle solutions, many of the data collected exhibit unexplained spatio-temporal fluctuations. Different candidates have been identified, the main ones being wall slip, interfacial instability between bands or bulk instability of one of the bands. In this review, we present experimental evidence for a purely elastic instability of the high shear rate band as the main origin for fluctuating shear-banding flows.

Influence of solvent on micellar morphologies of semifluorinated block copolymers.

PubMed

Lee, Min Young; Kim, Sang Jae; Jeong, Yeon Tae; Kim, Joo Hyun; Gal, Yeong-Soon; Lim, Kwon Taek

2009-12-01

The influence of solvents on micellar architectures of block copolymers composed of poly(1H,1H-dihydroperfluorooctyl methacrylate) and poly(ethylene oxide) was investigated. In this study, binary solvents with desired proportions were chosen, which had remarkable influence on the morphology of the resulting micelles. With simple adjusting the composition of the binary solvent of chloroform and trichlorofluoromethane, interesting shapes of micelle-like aggregates, such as core-shell, cylinder, worm-like and inverted micelles were formed with sizes of 15, 70, 30 and 250 nm, respectively. In the case of methanol/water system, core-shell spheres and vesicles were produced by varying the proportion of the contents. The morphologies were also tuned to honeycomb-like and bowl-shaped micelles as well as large planar lamellae with holes in DMF and water binary solvent.

A shear-induced network of aligned wormlike micelles in a sugar-based molecular gel. From gelation to biocompatibility assays.

PubMed

Fitremann, Juliette; Lonetti, Barbara; Fratini, Emiliano; Fabing, Isabelle; Payré, Bruno; Boulé, Christelle; Loubinoux, Isabelle; Vaysse, Laurence; Oriol, Luis

2017-10-15

A new low molecular weight hydrogelator with a saccharide (lactobionic) polar head linked by azide-alkyne click chemistry was prepared in three steps. It was obtained in high purity without chromatography, by phase separation and ultrafiltration of the aqueous gel. Gelation was not obtained reproducibly by conventional heating-cooling cycles and instead was obtained by shearing the aqueous solutions, from 2 wt% to 0.25 wt%. This method of preparation favored the formation of a quite unusual network of interconnected large but thin 2D-sheets (7nm-thick) formed by the association side-by-side of long and aligned 7nm diameter wormlike micelles. It was responsible for the reproducible gelation at the macroscopic scale. A second network made of helical fibres with a 10-13nm diameter, more or less intertwined was also formed but was scarcely able to sustain a macroscopic gel on its own. The gels were analysed by TEM (Transmission Electronic Microscopy), cryo-TEM and SAXS (Small Angle X-ray Scattering). Molecular modelling was also used to highlight the possible conformations the hydrogelator can take. The gels displayed a weak and reversible transition near 20°C, close to room temperature, ascribed to the wormlike micelles 2D-sheets network. Heating over 30°C led to the loss of the gel macroscopic integrity, but gel fragments were still observed in suspension. A second transition near 50°C, ascribed to the network of helical fibres, finally dissolved completely these fragments. The gels showed thixotropic behaviour, recovering slowly their initial elastic modulus, in few hours, after injection through a needle. Stable gels were tested as scaffold for neural cell line culture, showing a reduced biocompatibility. This new gelator is a clear illustration of how controlling the pathway was critical for gel formation and how a new kind of self-assembly was obtained by shearing. Copyright © 2017 Elsevier Inc. All rights reserved.

Mesoscale simulation of the formation and dynamics of lipid-structured poly(ethylene oxide)-block-poly(methyl methacrylate) diblock copolymers.

PubMed

Mu, Dan; Li, Jian-Quan; Feng, Sheng-Yu

2015-05-21

Twelve poly(ethylene oxide)-block-poly(methyl methacrylate) (PEO-b-PMMA) copolymers with lipid-like structures were designed and investigated by MesoDyn simulation. Spherical and worm-like micelles as well as bicontinuous, lamellar and defected lamellar phases were obtained. A special structure, designated B2412, with two lipid structures connected by their heads, was found to undergo four stages prior to forming a spherical micelle phase. Two possible assembly mechanisms were found via thermodynamic and dynamic process analyses; namely, the fusion and fission of micelles in dynamic equilibrium during the adjustment stage. Water can be encapsulated into these micelles, which can affect their size, particularly in low concentration aqueous solutions. The assignment of weak negative charges to the hydrophilic EO blocks resulted in a clear effect on micelle size. Surprisingly, the largest effect was observed with EO blocks with -0.5 e, wherein an ordered perfect hexagonal phase was formed. The obtained results can be applied in numerous fields of study, including adsorption, catalysis, controlled release and drug delivery.

Switching wormlike micelles of selenium-containing surfactant using redox reaction.

PubMed

Zhang, Yongmin; Kong, Weiwei; Wang, Cheng; An, Pengyun; Fang, Yun; Feng, Yujun; Qin, Zhirong; Liu, Xuefeng

2015-10-14

A novel redox-switchable wormlike micellar system was developed based on a mixture of selenium-containing zwitterionic surfactant and commercially available anionic surfactant sodium dodecyl sulfate, which reversibly and quickly responds to H2O2 and vitamin C, and shows circulatory gel/sol transition, reflecting changes in aggregate morphology from entangled worms to vesicles.

Conformation and structural changes of diblock copolymers with octopus-like micelle formation in the presence of external stimuli

NASA Astrophysics Data System (ADS)

Dammertz, K.; Saier, A. M.; Marti, O.; Amirkhani, M.

2014-04-01

External stimuli such as vapours and electric fields can be used to manipulate the formation of AB-diblock copolymers on surfaces. We study the conformational variation of PS-b-PMMA (polystyrene-block-poly(methyl methacrylate)), PS and PMMA adsorbed on mica and their response to saturated water or chloroform atmospheres. Using specimens with only partial polymer coverage, new unanticipated effects were observed. Water vapour, a non-solvent for all three polymers, was found to cause high surface mobility. In contrast, chloroform vapour (a solvent for all three polymers) proved to be less efficient. Furthermore, the influence of an additional applied electric field was investigated. A dc field oriented parallel to the sample surface induces the formation of polymer islands which assemble into wormlike chains. Moreover, PS-b-PMMA forms octopus-like micelles (OLMs) on mica. Under the external stimuli mentioned above, the wormlike formations of OLMs are able to align in the direction of the external electric field. In the absence of an electric field, the OLMs disaggregate and exhibit phase separated structures under chloroform vapour.

Ionic micelles and aromatic additives: a closer look at the molecular packing parameter.

PubMed

Lutz-Bueno, Viviane; Isabettini, Stéphane; Walker, Franziska; Kuster, Simon; Liebi, Marianne; Fischer, Peter

2017-08-16

Wormlike micellar aggregates formed from the mixture of ionic surfactants with aromatic additives result in solutions with impressive viscoelastic properties. These properties are of high interest for numerous industrial applications and are often used as model systems for soft matter physics. However, robust and simple models for tailoring the viscoelastic response of the solution based on the molecular structure of the employed additive are required to fully exploit the potential of these systems. We address this shortcoming with a modified packing parameter based model, considering the additive-surfactant pair. The role of charge neutralization on anisotropic micellar growth was investigated with derivatives of sodium salicylate. The impact of the additives on the morphology of the micellar aggregates is explained from the molecular level to the macroscopic viscoelasticity. Changes in the micelle's volume, headgroup area and additive structure are explored to redefine the packing parameter. Uncharged additives penetrated deeper into the hydrophobic region of the micelle, whilst charged additives remained trapped in the polar region, as revealed by a combination of 1 H-NMR, SAXS and rheological measurements. A deeper penetration of the additives densified the hydrophobic core of the micelle and induced anisotropic growth by increasing the effective volume of the additive-surfactant pair. This phenomenon largely influenced the viscosity of the solutions. Partially penetrating additives reduced the electrostatic repulsions between surfactant headgroups and neighboring micelles. The resulting increased network density governed the elasticity of the solutions. Considering a packing parameter composed of the additive-surfactant pair proved to be a facile means of engineering the viscoelastic response of surfactant solutions. The self-assembly of the wormlike micellar aggregates could be tailored to desired morphologies resulting in a specific and predictable rheological response.

Worming Their Way into Shape: Toroidal Formations in Micellar Solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cardiel Rivera, Joshua J.; Tonggu, Lige; Dohnalkova, Alice

2013-11-01

We report the formation of nanostructured toroidal micellar bundles (nTMB) from a semidilute wormlike micellar solution, evidenced by both cryogenicelectron microscopy and transmission electron microscopy images. Our strategy for creating nTMB involves a two-step protocol consisting of a simple prestraining process followed by flow through a microfluidic device containing an array of microposts, producing strain rates in the wormlike micelles on the order of 105 s^1. In combination with microfluidic confinement, these unusually large strain rates allow for the formation of stable nTMB. Electron microscopy images reveal a variety of nTMB morphologies and provide the size distribution of the nTMB.more » Small-angle neutron scattering indicates the underlying microstructural transition from wormlike micelles to nTMB. We also show that other flow-induced approaches such as sonication can induce and control the emergence of onion-like and nTMB structures, which may provide a useful tool for nanotemplating.« less

Flow of viscoelastic fluids around a sharp microfluidic bend: Role of wormlike micellar structure

NASA Astrophysics Data System (ADS)

Hwang, Margaret Y.; Mohammadigoushki, Hadi; Muller, Susan J.

2017-04-01

We examine the flow and instabilities of three viscoelastic fluids—a semidilute aqueous solution of polyethylene oxide (PEO) and two wormlike micellar solutions of cetylpyridinium chloride and sodium salicylate—around a microfluidic 90∘ bend, in which shear deformation and streamline curvature dominate. Similar to results reported by Gulati et al. [S. Gulati et al., Phys. Rev. E 78, 036314 (2008), 10.1103/PhysRevE.78.036314; S. Gulati et al., J. Rheol. 54, 375 (2010), 10.1122/1.3308643] for PEO solutions, we report a critical Weissenberg number (Wi) for the onset of lip vortex formation upstream of the corner. However, the decreased aspect ratio (channel depth to width) results in a slightly higher critical Wi and a vortex that grows more slowly. We consider wormlike micellar solutions of two salt to surfactant concentration ratios R =0.55 and R =0.79 . At R =0.55 , the wormlike micelles are linear and exhibit strong viscoelastic behavior, but at R =0.79 , the wormlike micelles become branched and exhibit shear-banding behavior. Microfluidic experiments on the R =0.55 solution reveal two flow transitions. The first transition, at Wi =6 , is characterized by the formation of a stationary lip vortex upstream of the bend; at the second transition, at Wi =20 , the vortex fluctuates in time and changes size. The R =0.79 solution also exhibits two transitions. The first transition at Wi =4 is characterized by the appearance of two intermittent vortices, one at the lip and one at the far outside corner. Increasing the flow rate to Wi >160 results in a transition to a second unstable regime, where there is only a lip vortex that fluctuates in size. The difference in flow transitions in PEO and wormlike micellar solutions presumably arises from the additional contribution of wormlike micellar breakage and reformation under shear. The flow transitions in wormlike micellar solutions are also significantly affected by chain branching.

Finger-like pattern formation in dilute surfactant pentaethylene glycol monododecyl ether solutions.

PubMed

Kubo, Yoshihide; Yokoyama, Yasuhiro; Tanaka, Shinpei

2013-04-07

We report here peculiar finger-like patterns observed during the phase separation process of dilute micellar pentaethylene glycol monododecyl ether solutions. The patterns were composed of parallel and periodic threads of micelle-rich domains. Prior to this pattern formation, the phase separation always started with the appearance of water-rich domains rimmed by the micelle-rich domains. It was found that these rims played a significant role in the pattern formation. We explain this pattern formation using a simple simulation model with disconnectable springs. The simulation results suggested that the spatially inhomogeneous elasticity or connectivity of a transient gel of worm-like micelles was responsible for the rim formation. The rims thus formed lead rim-induced nucleation, growth, and elongation of the domains owing to their small mobility and the elastic frustration around them. These rim-induced processes eventually produce the observed finger-like patterns.

Growth Behavior, Geometrical Shape, and Second CMC of Micelles Formed by Cationic Gemini Esterquat Surfactants.

PubMed

Bergström, L Magnus; Tehrani-Bagha, Alireza; Nagy, Gergely

2015-04-28

Micelles formed by novel gemini esterquat surfactants have been investigated with small-angle neutron scattering (SANS). The growth behavior of the micelles is found to differ conspicuously depending on the length of the gemini surfactant spacer group. The gemini surfactant with a long spacer form rather small triaxial ellipsoidal tablet-shaped micelles that grow weakly with surfactant concentration in the entire range of measured concentrations. Geminis with a short spacer, on the other hand, form weakly growing oblates or tablets at low concentrations that start to grow much more strongly into polydisperse rodlike or wormlike micelles at higher concentrations. The latter behavior is consistent with the presence of a second CMC that marks the transition from the weakly to the strongly growing regime. It is found that the growth behavior in terms of aggregation number as a function of surfactant concentration always appear concave in weakly growing regimes, while switching to convex behavior in strongly growing regimes. As a result, we are able to determine the second CMC of the geminis with short spacer by means of suggesting a rather precise definition of it, located at the point of inflection of the growth curve that corresponds to the transition from concave to convex growth behavior. Our SANS results are rationalized by comparison with the recently developed general micelle model. In particular, this theory is able to explain and reproduce the characteristic appearances of the experimental growth curves, including the presence of a second CMC and the convex strongly growing regime beyond. By means of optimizing the agreement between predictions from the general micelle model and results from SANS experiments, we are able to determine the three bending elasticity constants spontaneous curvature, bending rigidity, and saddle-splay constant for each surfactant.

Self-assembly of micelles in organic solutions of lecithin and bile salt: Mesoscale computer simulation

NASA Astrophysics Data System (ADS)

Markina, A.; Ivanov, V.; Komarov, P.; Khokhlov, A.; Tung, S.-H.

2016-11-01

We propose a coarse-grained model for studying the effects of adding bile salt to lecithin organosols by means of computer simulation. This model allows us to reveal the mechanisms of experimentally observed increasing of viscosity upon increasing the bile salt concentration. We show that increasing the bile salt to lecithin molar ratio induces the growth of elongated micelles of ellipsoidal and cylindrical shape due to incorporation of disklike bile salt molecules. These wormlike micelles can entangle into transient network displaying perceptible viscoelastic properties.

Cryo-TEM of morphology and kinetics of self-assembled nanostructures

NASA Astrophysics Data System (ADS)

Dong, Jingshan

Cryogenic Transmission Electron Microscopy (Cryo-TEM) is applied to study various structures in solutions and suspensions from micron to nanometer scale. By vitrifying the liquid samples at different moments, sequential stages of a dynamic process can be frozen and the structures occurring from about 30 sec to over 10 min can be imaged. Therefore a picture of how the structures evolve with time in the liquid systems can be established. This method has been proven to be a powerful technique in studying the morphology and kinetics of self-assembled nanostructures. Such a pseudo-in-situ technique is used to "watch" the crystallization process of silver stearate (AgSt) from sodium stearate (NaSt) dispersions. AgSt crystal is produced from a reaction of NaSt and silver nitrate. The reaction, as a AgSt crystallization process, starts from AgSt micelles, which aggregate and grow into hexagonal shaped crystals of about 10 microns. If silver bromide (AgBr) grains are present, the micelles do not prefer to aggregate, but rather deposit on the surface of the AgBr crystalline grains. Variation of the carboxylate chain length does not affect the crystallization process very much, although the morphology of both the reactant and the product is changed. Nanostructure transition in sodium lauryl ether sulfate (SLES) solutions is investigated as well. A micellar network structure can form if equal molar calcium chloride is added to 3 wt% SLES solution. The network can be broken into wormlike micelle segments such as spheres and rods by sonication. After about 10 min, these broken pieces can reassemble and reform the network through wormlike micelle growth and connection. Also by using Cryo-TEM, 100-200 nm casein micelles are observed at 1 wt% casein solution, but aggregated submicelles cannot be distinguished. However, individual submicelles of about 30 nm are indeed captured in a 0.03 wt% solution. By adding acid or EDTA, the casein micelles can be disrupted into small particles, the size of which is close to the estimated radius of gyration of single casein molecules.

Unsteady sedimentation of a sphere in wormlike micellar fluids

NASA Astrophysics Data System (ADS)

Zhang, Yiran; Muller, Susan J.

2018-04-01

The unsteady sedimentation of a sphere in wormlike micellar fluids is studied experimentally through shear and extensional rheometry, sphere trajectory tracking, and particle image velocimetry. Unsteady sphere sedimentation characterized by fluctuations in the sphere settling velocity was observed for a range of sphere size and density in two non-shear-banding wormlike micellar solutions, a cetylpyridinium chloride (CpCl)-sodium salicylate (NaSal) solution and a cetyltrimethylammonium p-toluenesulfonate (CTAT)-NaCl solution. The onset of the transition from steady to unsteady sphere motion is characterized by an extensional Deborah number, D eext , defined locally in the negative wake of the falling sphere. This instability criterion is in agreement with previous findings by Mohammadigoushki and Muller [J. Rheol. 60, 587 (2016), 10.1122/1.4948800] in the wormlike micelle system of cetyltrimethylammonium bromide (CTAB) and NaSal, and appears to be universally valid independent of micelle chemistry or solution rheology (e.g., shear banding or not). Moreover, the frequency at which the sphere velocity fluctuates is found to be linearly correlated with an average shear Deborah number D es , which is a measure of the overall flow strength. This suggests that a constant critical strain is accumulated before the flow instability takes place in each velocity oscillation. The velocity fluctuations are found to become increasingly disordered with increasing elastic Mach number, M ae , indicating that the interactions between the flow instability and elastic wave propagation result in more chaotic velocity fluctuations.

Self-assembly of amphiphilic molecules in organic liquids

NASA Astrophysics Data System (ADS)

Tung, Shih-Huang

2007-12-01

Amphiphilic molecules are well-known for their ability to self-assemble in water to form structures such as micelles and vesicles. In comparison, much less is known about amphiphilic self-assembly in nonpolar organic liquids. Such "reverse" self assembly can produce many of the counterparts to structures found in water. In this dissertation, we focus on the formation and dynamics of such reverse structures. We seek to obtain fundamental insight into the driving forces for reverse self-assembly processes. Three specific types of reverse structures are studied: (a) reverse wormlike micelles, i.e., long, flexible micellar chains; (b) reverse vesicles, i.e., hollow containers enclosed by reverse bilayers; and (c) organogel networks. While our focus is on the fundamentals, we note that reverse structures can be useful in a variety of applications ranging from drug delivery, controlled release, hosts for enzymatic reactions, and templates for nanomaterials synthesis. In the first part of this study, we describe a new route for forming reverse wormlike micelles in nonpolar organic liquids. This route involves the addition of trace amounts of a bile salt to solutions of the phospholipid, lecithin. We show that bile salts, due to their unique "facially amphiphilic" structure, can promote the aggregation of lecithin molecules into these reverse micellar chains. The resulting samples are viscoelastic and show interesting rheological properties. Unusual trends are seen in the temperature dependence of their rheology, which indicates the importance of hydrogen-bonding interactions in the formation of these micelles. Another remarkable feature of their rheology is the presence of strain-stiffening, where the material becomes stiffer at high deformations. Strain-stiffening has been seen before for elastic gels of biopolymers; here, we demonstrate the same properties for viscoelastic micellar solutions. The second reverse aggregate we deal with is the reverse vesicle. We present a new route for forming stable unilamellar reverse vesicles, and this involves mixing short- and long-chain lipids (lecithins) with a trace of sodium chloride. The ratio of the short to long-chain lipid controls the type and size of self-assembled structure formed, and as this ratio is increased, a transition from reverse micelles to vesicles occurs. The structural changes can be explained in terms of molecular geometry, with the sodium chloride acting as a "glue" in binding lipid headgroups together through electrostatic interactions. The final part of this dissertation focuses on organogels. The two-tailed anionic surfactant, AOT, is well-known to form spherical reverse micelles in organic solvents. We have found that trace amounts (e.g., less than 1 mM) of the dihydroxy bile salt, sodium deoxycholate (SDC) can transform these dilute micellar solutions into self-supporting, transparent organogels. The structure and rheology of these organogels is reminiscent of the self-assembled networks formed by proteins such as actin in water. The organogels are based on networks of long, rigid, cylindrical filaments, with SDC molecules stacked together in the filament core.

Sampling the kinetic pathways of a micelle fusion and fission transition.

PubMed

Pool, René; Bolhuis, Peter G

2007-06-28

The mechanism and kinetics of micellar breakup and fusion in a dilute solution of a model surfactant are investigated by path sampling techniques. Analysis of the path ensemble gives insight in the mechanism of the transition. For larger, less stable micelles the fission/fusion occurs via a clear neck formation, while for smaller micelles the mechanism is more direct. In addition, path analysis yields an appropriate order parameter to evaluate the fusion and fission rate constants using stochastic transition interface sampling. For the small, stable micelle (50 surfactants) the computed fission rate constant is a factor of 10 lower than the fusion rate constant. The procedure opens the way for accurate calculation of free energy and kinetics for, e.g., membrane fusion, and wormlike micelle endcap formation.

Mixtures of lecithin and bile salt can form highly viscous wormlike micellar solutions in water.

PubMed

Cheng, Chih-Yang; Oh, Hyuntaek; Wang, Ting-Yu; Raghavan, Srinivasa R; Tung, Shih-Huang

2014-09-02

The self-assembly of biological surfactants in water is an important topic for study because of its relevance to physiological processes. Two common types of biosurfactants are lecithin (phosphatidylcholine) and bile salts, which are both present in bile and involved in digestion. Previous studies on lecithin-bile salt mixtures have reported the formation of short, rodlike micelles. Here, we show that lecithin-bile salt micelles can be further induced to grow into long, flexible wormlike structures. The formation of long worms and their resultant entanglement into transient networks is reflected in the rheology: the fluids become viscoelastic and exhibit Maxwellian behavior, and their zero-shear viscosity can be up to a 1000-fold higher than that of water. The presence of worms is further confirmed by data from small-angle neutron and X-ray scattering and from cryo-transmission electron microscopy (cryo-TEM). We find that micellar growth peaks at a specific molar ratio (near equimolar) of bile salt:lecithin, which suggests a strong binding interaction between the two species. In addition, micellar growth also requires a sufficient concentration of background electrolyte such as NaCl or sodium citrate that serves to screen the electrostatic repulsion of the amphiphiles and to "salt out" the amphiphiles. We postulate a mechanism based on changes in the molecular geometry caused by bile salts and electrolytes to explain the micellar growth.

General Syntheses of Nanotubes Induced by Block Copolymer Self-Assembly.

PubMed

Zhao, Jianming; Huang, Wei; Si, Pengchao; Ulstrup, Jens; Diao, Fangyuan; Zhang, Jingdong

2018-06-01

Amphiphilic block copolymer templating strategies are extensively used for syntheses of mesoporous materials. However, monodisperse tubular nanostructures are limited. Here, a general method is developed to synthesize monodisperse nanotubes with narrow diameter distribution induced by self-assembly of block copolymer. 3-Aminophenol (AP) and formaldehyde (F) polymerize and self-assemble with cylindrical PS-b-PEO micelles into worm-like PS-b-PEO@APF composites with uniform diameter (49 ± 3 nm). After template extraction, worm-like APF polymer nanotubes are formed. The structure and morphology of the polymer nanotubes can be tuned by regulating the synthesis conditions. Furthermore, PS-b-PEO@APF composites are uniformly converted to isomorphic carbon nanotubes with large surface area of 662 m 2 g -1 , abundant hierarchical porous frameworks and nitrogen doping. The synthesis can be extended to silica nanotubes. These findings open an avenue to the design of porous materials with controlled structural framework, composition, and properties for a wide range of applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of platinum nanowire networks using a soft template.

PubMed

Song, Yujiang; Garcia, Robert M; Dorin, Rachel M; Wang, Haorong; Qiu, Yan; Coker, Eric N; Steen, William A; Miller, James E; Shelnutt, John A

2007-12-01

Platinum nanowire networks have been synthesized by chemical reduction of a platinum complex using sodium borohydride in the presence of a soft template formed by cetyltrimethylammonium bromide in a two-phase water-chloroform system. The interconnected polycrystalline nanowires possess the highest surface area (53 +/- 1 m2/g) and electroactive surface area (32.4 +/- 3.6 m2/g) reported for unsupported platinum nanomaterials; the high surface area results from the small average diameter of the nanowires (2.2 nm) and the 2-10 nm pores determined by nitrogen adsorption measurements. Synthetic control over the network was achieved simply by varying the stirring rate and reagent concentrations, in some cases leading to other types of nanostructures including wormlike platinum nanoparticles. Similarly, substitution of a palladium complex for platinum gives palladium nanowire networks. A mechanism of formation of the metal nanowire networks is proposed based on confined metal growth within a soft template consisting of a network of swollen inverse wormlike micelles.

Branching, Chain Scission, and Solution Stability of Worm-Like Micelles

NASA Astrophysics Data System (ADS)

Beaucage, Greg; Vogtt, Karsten; Jiang, Hanqui

As salt is added to a simple micelle solution such as SDS or SLES, the zero shear rate specific viscosity rises rapidly followed by a maximum and decay. The rapid rise in viscosity is associated with formation of elliptical and extended chain worm-like micelles, WLMs. Entanglement of these long chain micelles leads to the viscoelastic behavior we associate with shampoo and body wash. The plateau and drop in viscosity at high salt concentrations is caused by a special type of topological branching where the branch points have no energy penalty to motion along the chain according to Cates theory. These have some similarity to catenane crosslinks. Predictive dynamic theories for WLMs rely on structural details; the diameter, persistence length, contour length, branch length, segment length between branch points, and mesh size. Further, since the contour length and other large scale features are in kinetic equilibrium, with frequent chain breakage and formation, the thermodynamics of these long chain structures are of interest both in terms of chain scission as well as in terms of the stability of the colloidal solution as a whole. Recent structural studies of WLMs using static neutron scattering based on new scattering models will be presented demonstrating that these input parameters for dynamic models of complex topological systems are quantitatively and directly available. In this context it is important to consider a comparison between dynamic features, for instance entanglement, and their static analogs, chain overlap.

Self-assembly of nanocomposite materials

DOEpatents

Brinker, C. Jeffrey; Sellinger, Alan; Lu, Yunfeng

2001-01-01

A method of making a nanocomposite self-assembly is provided where at least one hydrophilic compound, at least one hydrophobic compound, and at least one amphiphilic surfactant are mixed in an aqueous solvent with the solvent subsequently evaporated to form a self-assembled liquid crystalline mesophase material. Upon polymerization of the hydrophilic and hydrophobic compounds, a robust nanocomposite self-assembled material is formed. Importantly, in the reaction mixture, the amphiphilic surfactant has an initial concentration below the critical micelle concentration to allow formation of the liquid-phase micellar mesophase material. A variety of nanocomposite structures can be formed, depending upon the solvent evaporazation process, including layered mesophases, tubular mesophases, and a hierarchical composite coating composed of an isotropic worm-like micellar overlayer bonded to an oriented, nanolaminated underlayer.

Light-Induced Gelling in a Micellar Fluid Based on a Zwitterionic Surfactant.

NASA Astrophysics Data System (ADS)

Kumar, Rakesh; Raghavan, Srinivasa

2007-03-01

Fluids with photoresponsive rheological properties (i.e. photorheological or PR fluids) can be useful in a range of applications, such as in dampers, sensors, and valves for microfluidic or MEMS devices. Previously, we have demonstrated a cationic surfactant-based PR fluid whose viscosity can be rapidly decreased by UV irradiation. This viscosity decrease was not reversible. Here, we describe a different formulation based on a zwitterionic surfactant that shows a rapid increase in viscosity (gelling) upon exposure to UV radiation. The formulation consists of the zwitterionic surfactant and a photosensitive cinnamic acid derivative. Initially, the viscosity of the fluid is low indicating the presence of small micelles. Upon UV irradiation, the cinnamic acid derivative is photoisomerized from trans to cis. In turn, the small micelles transform into long wormlike micelles, thus increasing the solution viscosity by more than five orders of magnitude. Small angle neutron scattering (SANS) data confirms the dramatic increase in micelle length. Possible reasons for such changes in micelle dimensions will be discussed.

Modeling the Inhomogeneous Response of Steady and Transient Flows of Entangled Micellar Solutions

NASA Astrophysics Data System (ADS)

McKinley, Gareth

2008-03-01

Surfactant molecules can self-assemble in solution into long flexible structures known as wormlike micelles. These structures entangle, forming a viscoelastic network similar to those in entangled polymer melts and solutions. However, in contrast to `inert' polymeric networks, wormlike micelles continuously break and reform leading to an additional relaxation mechanism and the name `living polymers'. Observations in both classes of entangled fluids have shown that steady and transient shearing flows of these solutions exhibit spatial inhomogeneities such as `shear-bands' at sufficiently large applied strains. In the present work, we investigate the dynamical response of a class of two-species elastic network models which can capture, in a self-consistent manner, the creation and destruction of elastically-active network segments, as well as diffusive coupling between the microstructural conformations and the local state of stress in regions with large spatial gradients of local deformation. These models incorporate a discrete version of the micellar breakage and reforming dynamics originally proposed by Cates and capture, at least qualitatively, non-affine tube deformation and chain disentanglement. The `flow curves' of stress and apparent shear rate resulting from an assumption of homogeneous deformation is non-monotonic and linear stability analysis shows that the region of non-monotonic response is unstable. Calculation of the full inhomogeneous flow field results in localized shear bands that grow linearly in extent across the gap as the apparent shear rate increases. Time-dependent calculations in step strain, large amplitude oscillatory shear (LAOS) and in start up of steady shear flow show that the velocity profile in the gap and the total stress measured at the bounding surfaces are coupled and evolve in a complex non-monotonic manner as the shear bands develop and propagate.

Dimensional control of supramolecular assemblies of diacetylene-derived peptide gemini amphiphile: from spherical micelles to foamlike networks.

PubMed

Jiang, Hao; Ehlers, Martin; Hu, Xiao-Yu; Zellermann, Elio; Schmuck, Carsten

2018-05-22

Peptide amphiphiles capable of assembling into multidimensional nanostructures have attracted much attention over the past decade due to their potential applications in materials science. Herein, a novel diacetylene-derived peptide gemini amphiphile with a fluorenylmethyloxycarbonyl (Fmoc) group at the N-terminus is reported to hierarchically assemble into spherical micelles, one-dimensional nanorods, two-dimensional foamlike networks and lamellae. Solvent polarity shows a remarkable effect on the self-assembled structures by changing the balance of four weak noncovalent interactions (hydrogen-bonding, π-π stacking, hydrophobic interaction, and electrostatic repulsion). We also show the time-evolution not only from spherical micelles to helical nanofibers in aqueous solution, but also from branched wormlike micelles to foamlike networks in methanol solution. In this work, the presence of the Fmoc group plays a key role in the self-assembly process. This work provides an efficient strategy for precise morphological control, aiding the future development in materials science.

Diffusing wave spectroscopy in Maxwellian fluids.

PubMed

Galvan-Miyoshi, J; Delgado, J; Castillo, R

2008-08-01

We present a critical assessment of the diffusing wave spectroscopy (DWS) technique for obtaining the characteristic lengths and for measuring the loss and storage moduli of a reasonable well-known wormlike micelle (WM) system. For this purpose, we tracked the Brownian motion of particles using DWS embedded in a Maxwellian fluid constituted by a wormlike micellar solution made of cetyltrimethylammonium bromide (CTAB), sodium salicylate (NaSal), and water. We found that the motion of particles was governed by the viscosity of the solvent at short times and by the stress relaxation mechanisms of the giant micelles at longer times. From the time evolution of the mean square displacement of particles, we could obtain for the WM solution the cage size where each particle is harmonically bound at short times, the long-time diffusion coefficient, and experimental values for the exponent that accounts for the broad spectrum of relaxation times at the plateau onset time found in the (deltar2(t)) vs. time curves. In addition, from the (deltar2(t)) vs. time curves, we obtained G'(omega) and G"(omega) for the WM solutions. All the DWS microreological information allowed us to estimate the characteristic lengths of the WM network. We compare our DWS microrheological results and characteristic lengths with those obtained with mechanical rheometers at different NaSal/CTAB concentration ratios and temperatures.

Viscoelastic fluid-structure interactions between a flexible cylinder and wormlike micelle solution

NASA Astrophysics Data System (ADS)

Dey, Anita A.; Modarres-Sadeghi, Yahya; Rothstein, Jonathan P.

2018-06-01

It is well known that when a flexible or flexibly mounted structure is placed perpendicular to the flow of a Newtonian fluid, it can oscillate due to the shedding of separated vortices at high Reynolds numbers. Unlike Newtonian fluids, the flow of viscoelastic fluids can become unstable even at infinitesimal Reynolds numbers due to a purely elastic flow instability that can occur at large Weissenberg numbers. Recent work has shown that these elastic flow instabilities can drive the motion of flexible sheets. The fluctuating fluid forces exerted on the structure from the elastic flow instabilities can lead to a coupling between an oscillatory structural motion and the state of stress in the fluid flow. In this paper, we present the results of an investigation into the flow of a viscoelastic wormlike micelle solution past a flexible circular cylinder. The time variation of the flow field and the state of stress in the fluid are shown using a combination of particle image tracking and flow-induced birefringence images. The static and dynamic responses of the flexible cylinder are presented for a range of flow velocities. The nonlinear dynamics of the structural motion is studied to better understand an observed transition from a symmetric to an asymmetric structural deformation and oscillation behavior.

Nano-assembly of Surfactants with Interfacial Drug-Interactive Motifs as Tailor-Designed Drug Carriers

PubMed Central

Gao, Xiang; Huang, Yixian; Makhov, Alexander M.; Epperly, Michael; Lu, Jianqin; Grab, Sheila; Zhang, Peijun; Rohan, Lisa; Xie, Xiang-qun (Sean); Wipf, Peter; Greenberger, Joel; Li, Song

2012-01-01

PEGylated lipopeptide surfactants carrying drug-interactive motifs specific for a peptide-nitroxide antioxidant, JP4-039, were designed and constructed to facilitate the solubilization of this drug candidate as micelles and emulsion nanoparticles. A simple screening process based on the ability that prevents the formation of crystals of JP4-039 in aqueous solution was used to identify agents that have potential drug-interactive activities. Several protected lysine derivatives possessing this activity were identified, of which α-Fmoc-ε-tBoc lysine is the most potent, followed by α-Cbz- and α-iso-butyloxycarbonyl-ε-tBoc-lysine. Using polymer-supported liquid-phase synthesis approach, a series of synthetic lipopeptide surfactants with PEG head group, varied numbers and geometries of α-Fmoc or α-Cbz-lysyl groups located at interfacial region as the drug-interactive domains, and oleoyl chains as the hydrophobic tails were synthesized. All α-Fmoc-lysyl-containing lipopeptide surfactants were able to solubilize JP4-039 as micelles, with enhanced solubilizing activity for surfactants with increased numbers of α-Fmoc groups. The PEGylated lipopeptide surfactants with α-Fmoc-lysyl groups alone tend to form filamentous or worm-like micelles. The presence of JP4-039 transformed α-Fmoc-containing filamentous micelles into dots and bar-like mixed micelles with substantially reduced sizes. Fluorescence quenching and NMR studies revealed that the drug and surfactant molecules were in a close proximity in the complex. JP4-039-loaded emulsion carrying α-Cbz-containing surfactants demonstrated enhanced stability over drug loaded emulsion without lipopeptide surfactants. JP4-039-emulsion showed significant mitigation effect on mice exposed to a lethal dose of radiation. PEGylated lipopeptides with an interfacially located drug-interactive domain are therefore tailor-designed formulation materials potentially useful for drug development. PMID:23244299

pH-Responsive Wormlike Micelles with Sequential Metastasis Targeting Inhibit Lung Metastasis of Breast Cancer.

PubMed

He, Xinyu; Yu, Haijun; Bao, Xiaoyue; Cao, Haiqiang; Yin, Qi; Zhang, Zhiwen; Li, Yaping

2016-02-18

Cancer metastasis is the main cause for the high mortality in breast cancer patients. Herein, we first report succinobucol-loaded pH-responsive wormlike micelles (PWMs) with sequential targeting capability to inhibit lung metastasis of breast cancer. PWMs can in a first step be delivered specifically to the sites of metastases in the lungs and then enable the intracellular pH-stimulus responsive drug release in cancer cells to improve the anti-metastatic effect. PWMs are identified as nanofibrillar assemblies with a diameter of 19.9 ± 1.9 nm and a length within the 50-200 nm range, and exhibited pH-sensitive drug release behavior in response to acidic intracellular environments. Moreover, PWMs can obviously inhibit the migration and invasion abilities of metastatic 4T1 breast cancer cells, and reduce the expression of the metastasis-associated vascular cell adhesion molecule-1 (VCAM-1) at 400 ng mL(-1) of succinobucol. In particular, PWMs can induce a higher specific accumulation in lung and be specifically delivered to the sites of metastases in lung, thereby leading to an 86.6% inhibition on lung metastasis of breast cancer. Therefore, the use of sequentially targeting PWMs can become an encouraging strategy for specific targeting and effective treatment of cancer metastasis. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Effect of counterion binding efficiency on structure and dynamics of wormlike micelles.

PubMed

Oelschlaeger, C; Suwita, P; Willenbacher, N

2010-05-18

We have studied the effect of counterion binding efficiency on the linear viscoelastic properties of wormlike micelles formed from hexadecyltrimethylammonium bromide (CTAB) in the presence of different nonpenetrating inorganic salts: potassium bromide (KBr), sodium nitrate (NaNO(3)), and sodium chlorate (NaClO(3)). We have varied the salt/surfactant ratio R at fixed surfactant concentration of 350 mM. Results are compared to data for the system cetylpyridinium chloride (CPyCl) and the penetrating counterion sodium salicylate (NaSal) (Oelschlaeger, C.; Schopferer, M.; Scheffold, F.; Willenbacher, N. Langmuir 2009, 25, 716-723). Mechanical high-frequency rheology and diffusing wave spectroscopy (DWS) based tracer microrheology are used to determine the shear moduli G' and G'' in the frequency range from 0.1 Hz up to 1 MHz (Willenbacher, N.; Oelschlaeger, C.; Schopferer, M.; Fischer, P.; Cardinaux, F.; Scheffold, F. Phys. Rev. Lett. 2007, 99, 068302, 1-4). This enables us to determine the plateau modulus G(0), which is related to the cross-link density or mesh size of the entanglement network, the bending stiffness kappa (also expressed as persistence length l(p) = kappa/k(B)T) corresponding to the semiflexible nature of the micelles, and the scission energy E(sciss), which is related to their contour length. The viscosity maximum shifts to higher R values, and the variation of viscosity with R is less pronounced as the binding strength decreases. The plateau modulus increases with R at low ionic strength and is constant around the viscosity maximum; the increase in G(0) at high R, which is presumably due to branching, is weak compared to the system with penetrating counterion. The scission energy E(sciss) approximately = 20 k(B)T is independent of counterion binding efficiency irrespective of R and is slightly higher compared to the system CPyCl/NaSal, indicating that branching may be significant already at the viscosity maximum in this latter case. The micellar flexibility increases with increasing binding efficiency of counterions according to the Hofmeister series. The persistence length values for systems CTAB/KBr, CTAB/NaNO(3), and CTAB/NaClO(3) are 40, 34, and 29 nm, respectively, independent of R, and are significantly higher than in the case of CPyCl/NaSal.

Mechanistic insights for block copolymer morphologies: how do worms form vesicles?

PubMed

Blanazs, Adam; Madsen, Jeppe; Battaglia, Giuseppe; Ryan, Anthony J; Armes, Steven P

2011-10-19

Amphiphilic diblock copolymers composed of two covalently linked, chemically distinct chains can be considered to be biological mimics of cell membrane-forming lipid molecules, but with typically more than an order of magnitude increase in molecular weight. These macromolecular amphiphiles are known to form a wide range of nanostructures (spheres, worms, vesicles, etc.) in solvents that are selective for one of the blocks. However, such self-assembly is usually limited to dilute copolymer solutions (<1%), which is a significant disadvantage for potential commercial applications such as drug delivery and coatings. In principle, this problem can be circumvented by polymerization-induced block copolymer self-assembly. Here we detail the synthesis and subsequent in situ self-assembly of amphiphilic AB diblock copolymers in a one pot concentrated aqueous dispersion polymerization formulation. We show that spherical micelles, wormlike micelles, and vesicles can be predictably and efficiently obtained (within 2 h of polymerization, >99% monomer conversion) at relatively high solids in purely aqueous solution. Furthermore, careful monitoring of the in situ polymerization by transmission electron microscopy reveals various novel intermediate structures (including branched worms, partially coalesced worms, nascent bilayers, "octopi", "jellyfish", and finally pure vesicles) that provide important mechanistic insights regarding the evolution of the particle morphology during the sphere-to-worm and worm-to-vesicle transitions. This environmentally benign approach (which involves no toxic solvents, is conducted at relatively high solids, and requires no additional processing) is readily amenable to industrial scale-up, since it is based on commercially available starting materials.

CO2/pH-Controllable Viscoelastic Nanostructured Fluid Based on Stearic Acid Soap and Bola-Type Quaternary Ammonium Salt.

PubMed

Zhang, Yongmin; Kong, Weiwei; An, Pengyun; He, Shuai; Liu, Xuefeng

2016-03-15

Fatty acid soaps such as sodium stearate (NaOSA) represent a class of cheap, environmentally friendly surfactants; however, their poor solubility seriously challenges their application in various fields. Herein, we describe a CO2/pH-controllable viscoelastic nanostructured fluid, which was developed by simple mixing of the commodity soap NaOSA with a bola-type quaternary ammonium salt (Bola2be) in a 2:1 molar ratio without the need for complex organic synthesis. The introduction of Bola2be increased NaOSA solubility and promoted micelle growth by forming a noncovalent pseudo-Gemini structure, 2NaOSA-Bola2be. Long aggregates are formed with increases in concentration, and these become entangled into a three-dimensional network at 10 times that of the critical micelle concentration (0.057 mM), showing strong thickening ability. Micellar branching occurs above 22.38 mM, as deduced by rheology and verified by cryo-transmission electron microscopy. The worm-based fluid formed from the noncovalent pseudo-Gemini surfactant is highly thermosensitive, and features a higher flow activation energy of 399.76 kJ·mol(-1) compared with common worm systems. Because of the pH-sensitivity of NaOSA, the viscoelastic fluid can respond to common pH stimuli or green CO2 gas, and shows a transition between a gel-like wormlike micellar network and a water-like dispersion with precipitate. However, the CO2-responsive behavior is irreversible.

Phase separation in solution of worm-like micelles: a dilute ? spin-vector model

NASA Astrophysics Data System (ADS)

Panizza, Pascal; Cristobal, Galder; Curély, Jacques

1998-12-01

We show how the dilute 0953-8984/10/50/006/img2 spin vector model introduced originally by Wheeler and co-workers for describing the polymerization phenomenon in solutions of liquid sulphur and of living polymers may be conveniently adapted for studying phase separation in systems containing long flexible micelles. We draw an isomorphism between the coupling constant appearing in the exchange Hamiltonian and the surfactant energies in the micellar problem. We solve this problem within the mean-field approximation and compare the main results we have obtained with respect to polymer theory and previous theories of phase separation in micellar solutions. We show that the attractive interaction term 0953-8984/10/50/006/img3 between monomers renormalizes the aggregation energy and subsequently the corresponding size distribution. Under these conditions, we observe that the general aspect of the phase diagram in the 0953-8984/10/50/006/img4 plane (where 0953-8984/10/50/006/img5 is the surfactant concentration) is different from previous results. The spinodal line shows a re-entrant behaviour and, at low concentrations, we point out the possibility of specific nucleation phenomena related to the existence of a metastable transition line between a region composed of spherical micelles and another one corresponding to a dilute solution of long flexible micelles.

Preparation of wormlike polymeric nanoparticles coated with silica for delivery of methotrexate and evaluation of anticancer activity against MCF7 cells.

PubMed

Gharebaghi, Farhad; Dalali, Naser; Ahmadi, Ebrahim; Danafar, Hossein

2017-04-01

Methotrexate is one of the most effective drugs that is commonly used in the treatment of cancer. However, its application is limited due to low solubility, high toxicity and rapid metabolism. Therefore, in the present study, worm-like polymeric nanoparticles as carrier of methotrexate were prepared using biodegradable copolymers (mPEG-PCL). The impact of nanoparticles' geometry on the loading, delivery and drug's anti-cancer activity was investigated. The di-block copolymer mPEG-PCL was being synthesized by a ring opening polymerization of ɛ-caprolactone in the presence of mPEG as the initiator and Sn(oct) 2 as the catalyst. It was used for the preparation of worm-like micelles and coated with silica, so that their structures are stable after drying. The synthesized copolymers and nanoparticles were characterized by FTIR, HNMR, GPC, XRD, TGA, DLS, and FE-SEM analyses. The efficiencies of drug loading and release of nanoparticles as in vitro, was studied by high performance liquid chromatography. The MTT method was used to estimate the toxicity on MCF-7 cell category. The obtained results showed that the nanoparticles were worm-like particles with less than 150 nm diameter and about 1 µm length. The loading and encapsulation efficiencies of drug by the worm-like nanoparticles were 3.5 ± 0.14% and 65.6 ± 0.12%, respectively, while they were obtained as 2.1 ± 0.08% and 26 ± 0.10%, respectively, for spherical nanoparticles. The methotrexate diffusional behavior of worm-like nanoparticles was compared with that of the spherical ones. On the other hand, the anti-cancer activity of MTX-loaded nanoparticles was more than the free drug. The results of the MTT assay showed strong and dose-dependent inhibition of cell (MCF-7 category) growth by the nanoparticles compared with MTX. The inhibitory concentrations (IC 50 i.e. reduction viability of cell to 50%) obtained for worm-like, spherical nanoparticles and free drug (incubation times 72 h) were 8.25 ± 0.20, 9.15 ± 0.17, 12.28 ± 0.15 µg/mL, respectively. It can be concluded that application of non-spherical nanoparticles is a better and more effective strategy for controlled and slow release of methotrexate in the treatment of cancer.

Hydrogen Bonding-Mediated Microphase Separation during the Formation of Mesoporous Novolac-Type Phenolic Resin Templated by the Triblock Copolymer, PEO-b-PPO-b-PEO

PubMed Central

Chu, Wei-Cheng; Chiang, Shih-Fan; Li, Jheng-Guang; Kuo, Shiao-Wei

2013-01-01

After blending the triblock copolymer, poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (PEO-b-PPO-b-PEO) with novolac-type phenolic resin, Fourier transform infrared spectroscopy revealed that the ether groups of the PEO block were stronger hydrogen bond acceptors for the OH groups of phenolic resin than were the ether groups of the PPO block. Thermal curing with hexamethylenetetramine as the curing agent resulted in the triblock copolymer being incorporated into the phenolic resin, forming a nanostructure through a mechanism involving reaction-induced microphase separation. Mild pyrolysis conditions led to the removal of the PEO-b-PPO-b-PEO triblock copolymer and formation of mesoporous phenolic resin. This approach provided a variety of composition-dependent nanostructures, including disordered wormlike, body-centered-cubic spherical and disorder micelles. The regular mesoporous novolac-type phenolic resin was formed only at a phenolic content of 40–60 wt %, the result of an intriguing balance of hydrogen bonding interactions among the phenolic resin and the PEO and PPO segments of the triblock copolymer. PMID:28788378

Flexible Epoxy Resin Formed Upon Blending with a Triblock Copolymer through Reaction-Induced Microphase Separation

PubMed Central

Chu, Wei-Cheng; Lin, Wei-Sheng; Kuo, Shiao-Wei

2016-01-01

In this study, we used diglycidyl ether bisphenol A (DGEBA) as a matrix, the ABA block copolymer poly(ethylene oxide–b–propylene oxide–b–ethylene oxide) (Pluronic F127) as an additive, and diphenyl diaminosulfone (DDS) as a curing agent to prepare flexible epoxy resins through reaction-induced microphase separation (RIMPS). Fourier transform infrared spectroscopy confirmed the existence of hydrogen bonding between the poly(ethylene oxide) segment of F127 and the OH groups of the DGEBA resin. Small-angle X-ray scattering, atomic force microscopy, and transmission electron microscopy all revealed evidence for the microphase separation of F127 within the epoxy resin. Glass transition temperature (Tg) phenomena and mechanical properties (modulus) were determined through differential scanning calorimetry and dynamic mechanical analysis, respectively, of samples at various blend compositions. The modulus data provided evidence for the formation of wormlike micelle structures, through a RIMPS mechanism, in the flexible epoxy resin upon blending with the F127 triblock copolymer. PMID:28773571

Structural transformations in diluted micellar and lamellar systems

NASA Astrophysics Data System (ADS)

Zelaya-Rincon, Blanca

The role of dilution by artificial hard water on nanostructures present in body wash samples provided by Procter and Gamble were investigated using time-resolved cryogenic transmission electron microscopy (cryo-TEM). Samples with and without perfume were examined at 10X, 20X, and 50X dilution. Micellar samples transformed to mostly unilamellar vesicles at 50X dilution, in contrast to the micelle to monomer transition seen in typical samples. At lower dilutions, a change in morphology from spherical to wormlike micelles was observed. For lamellar samples, lower dilution ratios show tightly packed multilamellar vesicles, while higher dilution ratios show more dispersed vesicles with less bilayers. Nanostructural transformations upon dilution were attributed to changes in curvature/packing parameters, which occurred due to dilution with hard water and addition of perfume. The systems experience changes in curvature in order to maintain equilibrium. Also, the addition of perfume in the lamellar samples caused an increase in the number of bilayers present in multilamellar vesicles, because of its role in increasing the packing parameter in the system.

Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups.

PubMed

Martin, Adam D; Wojciechowski, Jonathan P; Robinson, Andrew B; Heu, Celine; Garvey, Christopher J; Ratcliffe, Julian; Waddington, Lynne J; Gardiner, James; Thordarson, Pall

2017-03-08

Using small angle neutron scattering (SANS), it is shown that the existence of pre-assembled structures at high pH for a capped diphenylalanine hydrogel is controlled by the selection of N-terminal heterocyclic capping group, namely indole or carbazole. At high pH, changing from a somewhat hydrophilic indole capping group to a more hydrophobic carbazole capping group results in a shift from a high proportion of monomers to self-assembled fibers or wormlike micelles. The presence of these different self-assembled structures at high pH is confirmed through NMR and circular dichroism spectroscopy, scanning probe microscopy and cryogenic transmission electron microscopy.

Rupturing the hemi-fission intermediate in membrane fission under tension: Reaction coordinates, kinetic pathways, and free-energy barriers

NASA Astrophysics Data System (ADS)

Zhang, Guojie; Müller, Marcus

2017-08-01

Membrane fission is a fundamental process in cells, involved inter alia in endocytosis, intracellular trafficking, and virus infection. Its underlying molecular mechanism, however, is only incompletely understood. Recently, experiments and computer simulation studies have revealed that dynamin-mediated membrane fission is a two-step process that proceeds via a metastable hemi-fission intermediate (or wormlike micelle) formed by dynamin's constriction. Importantly, this hemi-fission intermediate is remarkably metastable, i.e., its subsequent rupture that completes the fission process does not occur spontaneously but requires additional, external effects, e.g., dynamin's (unknown) conformational changes or membrane tension. Using simulations of a coarse-grained, implicit-solvent model of lipid membranes, we investigate the molecular mechanism of rupturing the hemi-fission intermediate, such as its pathway, the concomitant transition states, and barriers, as well as the role of membrane tension. The membrane tension is controlled by the chemical potential of the lipids, and the free-energy landscape as a function of two reaction coordinates is obtained by grand canonical Wang-Landau sampling. Our results show that, in the course of rupturing, the hemi-fission intermediate undergoes a "thinning → local pinching → rupture/fission" pathway, with a bottle-neck-shaped cylindrical micelle as a transition state. Although an increase of membrane tension facilitates the fission process by reducing the corresponding free-energy barrier, for biologically relevant tensions, the free-energy barriers still significantly exceed the thermal energy scale kBT.

Rupturing the hemi-fission intermediate in membrane fission under tension: Reaction coordinates, kinetic pathways, and free-energy barriers.

PubMed

Zhang, Guojie; Müller, Marcus

2017-08-14

Membrane fission is a fundamental process in cells, involved inter alia in endocytosis, intracellular trafficking, and virus infection. Its underlying molecular mechanism, however, is only incompletely understood. Recently, experiments and computer simulation studies have revealed that dynamin-mediated membrane fission is a two-step process that proceeds via a metastable hemi-fission intermediate (or wormlike micelle) formed by dynamin's constriction. Importantly, this hemi-fission intermediate is remarkably metastable, i.e., its subsequent rupture that completes the fission process does not occur spontaneously but requires additional, external effects, e.g., dynamin's (unknown) conformational changes or membrane tension. Using simulations of a coarse-grained, implicit-solvent model of lipid membranes, we investigate the molecular mechanism of rupturing the hemi-fission intermediate, such as its pathway, the concomitant transition states, and barriers, as well as the role of membrane tension. The membrane tension is controlled by the chemical potential of the lipids, and the free-energy landscape as a function of two reaction coordinates is obtained by grand canonical Wang-Landau sampling. Our results show that, in the course of rupturing, the hemi-fission intermediate undergoes a "thinning → local pinching → rupture/fission" pathway, with a bottle-neck-shaped cylindrical micelle as a transition state. Although an increase of membrane tension facilitates the fission process by reducing the corresponding free-energy barrier, for biologically relevant tensions, the free-energy barriers still significantly exceed the thermal energy scale k B T.

Phase diagrams of block copolymer melts by dissipative particle dynamics simulations

NASA Astrophysics Data System (ADS)

Gavrilov, Alexey A.; Kudryavtsev, Yaroslav V.; Chertovich, Alexander V.

2013-12-01

Phase diagrams for monodisperse and polydisperse diblock copolymer melts and a random multiblock copolymer melt are constructed using dissipative particle dynamics simulations. A thorough visual analysis and calculation of the static structure factor in several hundreds of points at each of the diagrams prove the ability of mesoscopic molecular dynamics to predict the phase behavior of polymer systems as effectively as the self-consistent field-theory and Monte Carlo simulations do. It is demonstrated that the order-disorder transition (ODT) curve for monodisperse diblocks can be precisely located by a spike in the dependence of the mean square pressure fluctuation on χN, where χ is the Flory-Huggins parameter and N is the chain length. For two other copolymer types, the continuous ODTs are observed. Large polydispersity of both blocks obeying the Flory distribution in length does not shift the ODT curve but considerably narrows the domains of the cylindrical and lamellar phases partially replacing them with the wormlike micelle and perforated lamellar phases, respectively. Instead of the pure 3d-bicontinuous phase in monodisperse diblocks, which could be identified as the gyroid, a coexistence of the 3d phase and cylindrical micelles is detected in polydisperse diblocks. The lamellar domain spacing D in monodisperse diblocks follows the strong-segregation theory prediction, D/N1/2 ˜ (χN)1/6, whereas in polydisperse diblocks it is almost independent of χN at χN < 100. Completely random multiblock copolymers cannot form ordered microstructures other than lamellas at any composition.

Biomimetic oral mucin from polymer micelle networks

NASA Astrophysics Data System (ADS)

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-functional implant coats. KEYWORDS: Biomimic, Bioapplication, Drug delivery, Filomicelle, Mucin, Polymer networks.

Controlling self-assembly of diphenylalanine peptides at high pH using heterocyclic capping groups

PubMed Central

Martin, Adam D.; Wojciechowski, Jonathan P.; Robinson, Andrew B.; Heu, Celine; Garvey, Christopher J.; Ratcliffe, Julian; Waddington, Lynne J.; Gardiner, James; Thordarson, Pall

2017-01-01

Using small angle neutron scattering (SANS), it is shown that the existence of pre-assembled structures at high pH for a capped diphenylalanine hydrogel is controlled by the selection of N-terminal heterocyclic capping group, namely indole or carbazole. At high pH, changing from a somewhat hydrophilic indole capping group to a more hydrophobic carbazole capping group results in a shift from a high proportion of monomers to self-assembled fibers or wormlike micelles. The presence of these different self-assembled structures at high pH is confirmed through NMR and circular dichroism spectroscopy, scanning probe microscopy and cryogenic transmission electron microscopy. PMID:28272523

Strip waves in vibrated shear-thickening wormlike micellar solutions

NASA Astrophysics Data System (ADS)

Epstein, T.; Deegan, R. D.

2010-06-01

We present an instability in vertically vibrated dilute wormlike micellar solutions. Above a critical driving acceleration the fluid forms elongated solitary domains of high amplitude waves. We model this instability using a Mathieu equation modified to account for the non-Newtonian character of the fluid. We find that our model successfully reproduces the observed transitions.

Formation of wormlike aggregates of fluorocarbon-hydrocarbon hybrid surfactant by Langmuir-Blodgett transfer and alignment of gold nanoparticles.

PubMed

Kondo, Yukishige; Fukuoka, Hiroshi; Nakano, Shuichi; Hayashi, Kohei; Tsukagoshi, Tatsuya; Matsumoto, Mutsuyoshi; Yoshino, Norio

2007-05-22

A novel anionic fluorocarbon-hydrocarbon hybrid surfactant (SS-Hyb-Na+) with a disulfide group has been synthesized from 11-bromo-1-undecanal and perfluorohexylethyl iodide via three steps. The Langmuir-Blodgett (LB) transfer of the 1:100 (mol/mol) mixed monolayer of SS-Hyb-Na+ and stearyl alcohol (C18OH) formed on an aqueous solution containing a cationic polymer, poly(diallyldimethylammonium chloride) (PDDA+Cl-) onto a hydrophobic silicon wafer yields the formation of wormlike aggregates consisting of SS-Hyb-/PDDA+ polyion complexes. It is found that the aggregates align along the withdrawal direction of the wafer substrate. When the wafer on which the wormlike aggregates exist is immersed into the dispersion of gold nanoparticles (Au NPs) prepared by the citrate reduction method, Au NPs align along the wormlike structures. Even though the surface of the wafer is placed either vertical or parallel to the monolayer compression direction during the LB transfer, the one-dimensional (1D) array of Au NPs is observed along the withdrawal direction of the wafer. This indicates that the wormlike aggregates of SS-Hyb-/PDDA+ complexes are aligned during the LB transfer, and the aligned aggregates behave as a scaffold in the 1D array of Au NPs.

Jetting of a shear banding fluid in rectangular ducts

PubMed Central

Salipante, Paul F.; Little, Charles A. E.; Hudson, Steven D.

2017-01-01

Non-Newtonian fluids are susceptible to flow instabilities such as shear banding, in which the fluid may exhibit a markedly discontinuous viscosity at a critical stress. Here we report the characteristics and causes of a jetting flow instability of shear banding wormlike micelle solutions in microfluidic channels with rectangular cross sections over an intermediate volumetric flow regime. Particle-tracking methods are used to measure the three-dimensional flow field in channels of differing aspect ratios, sizes, and wall materials. When jetting occurs, it is self-contained within a portion of the channel where the flow velocity is greater than the surroundings. We observe that the instability forms in channels with aspect ratio greater than 5, and that the location of the high-velocity jet appears to be sensitive to stress localizations. Jetting is not observed in a lower concentration solution without shear banding. Simulations using the Johnson-Segalman viscoelastic model show a qualitatively similar behavior to the experimental observations and indicate that compressive normal stresses in the cross-stream directions support the development of the jetting flow. Our results show that nonuniform flow of shear thinning fluids can develop across the wide dimension in rectangular microfluidic channels, with implications for microfluidic rheometry. PMID:28691108

Self-Assemblies of novel molecules, VECAR

NASA Astrophysics Data System (ADS)

Shrestha, Bijay; Kim, Hye-Young; Lee, Soojin; Novak, Brian; Moldovan, Dorel

2015-03-01

VECAR is a newly synthesized molecule, which is an amphiphilic antioxidant molecule that consists of two molecular groups, vitamin-E and Carnosine, linked by a hydrocarbon chain. The hydrocarbon chain is hydrophobic and both vitamin-E and Carnosine ends are hydrophilic. In the synthesis process, the length of the hydrophobic chain of VECAR molecules can vary from the shortest (n =0) to the longest (n =18), where n indicates the number of carbon atoms in the chain. We conducted MD simulation studies of self-assembly of VECAR molecules in water using GROMACS on LONI HPC resources. Our study shows that there is a strong correlation between the shape and atomistic structure of the self-assembled nano-structures (SANs) and the chain-length (n) of VECAR molecules. We will report the results of data analyses including the atomistic structure of each SANs and the dynamic and energetic mechanisms of their formation as function of time. In summary, both VECAR molecules of chain-length n =18 and 9 form worm-like micelles, which may be used as a drug delivery system. This research is supported by the Louisiana Board of Regents-RCS Grant (LEQSF(2012-15)-RD-A-19).

Fiber lubrication: A molecular dynamics simulation study

NASA Astrophysics Data System (ADS)

Liu, Hongyi

Molecular and mesoscopic level description of friction and lubrication remains a challenge because of difficulties in the phenomenological understanding of to the behaviors of solid-liquid interfaces during sliding. Fortunately, there is the computational simulation approach opens an opportunity to predict and analyze interfacial phenomena, which were studied with molecular dynamics (MD) and mesoscopic dynamics (MesoDyn) simulations. Polypropylene (PP) and cellulose are two of most common polymers in textile fibers. Confined amorphous surface layers of PP and cellulose were built successfully with xenon crystals which were used to compact the polymers. The physical and surface properties of the PP and cellulose surface layers were investigated by MD simulations, including the density, cohesive energy, volumetric thermal expansion, and contact angle with water. The topology method was employed to predict the properties of poly(alkylene glycol) (PAG) diblock copolymers and Pluronic triblock copolymers used as lubricants on surfaces. Density, zero shear viscosity, shear module, cohesive energy and solubility parameter were predicted with each block copolymer. Molecular dynamics simulations were used to study the interaction energy per unit contact area of block copolymer melts with PP and cellulose surfaces. The interaction energy is defined as the ratio of interfacial interaction energy to the contact area. Both poly(proplene oxide) (PPO) and poly(ethylene oxide) (PEO) segments provided a lipophilic character to both PP and cellulose surfaces. The PPO/PEO ratio and the molecular weight were found to impact the interaction energy on both PP and cellulose surfaces. In aqueous solutions, the interaction energy is complicated due to the presence of water and the cross interactions between the multiple molecular components. The polymer-water-surface (PWS) calculation method was proposed to calculate such complex systems. In a contrast with a vacuum condition, the presence of water increases the attractive interaction energy of the diblock copolymer on the cellulose surface, compared with that on the PP surface. Water decreases the interaction energy of the triblock copolymer on the cellulose surface, compared with that on the PP surface. MesoDyn was adopted to investigate the self-assembled morphology of the triblock copolymer, in aqueous solution, confined and sheared at solid-liquid interfaces. In a bulk aqueous solution, when the polymer concentration reached 10% v/v, micelles were observed with PPO blocks in the core and PEO blocks in the shell of the micelles. At the concentrations of 25% and 50%, worm-like micelles and irregular cylinders were observed in solutions, respectively. The micelles were formed faster in aqueous solutions confined by cellulose surfaces than that in the bulk. The formed micelles were broken under shearing, which led to a depletion of polymers at the interfaces. During the shearing on the PP surfaces, the polymers were adsorbed on the surfaces protecting the PP surfaces. This simulation study in the fiber lubrication was in good agreement with the experimental results and so provided an approach to visualize the polymer configuration at the liquid-solid interface, predict the lubricant-surface systems, and theoretically guide the experiments of designing new/efficient lubricants for fibers.

Shear-banding and superdiffusivity in entangled polymer solutions

NASA Astrophysics Data System (ADS)

Shin, Seunghwan; Dorfman, Kevin D.; Cheng, Xiang

2017-12-01

Using high-resolution confocal rheometry, we study the shear profiles of well-entangled DNA solutions under large-amplitude oscillatory shear in a rectilinear planar shear cell. With increasing Weissenberg number (Wi), we observe successive transitions from normal Newtonian linear shear profiles to wall-slip dominant shear profiles and, finally, to shear-banding profiles at high Wi. To investigate the microscopic origin of the observed shear banding, we study the dynamics of micron-sized tracers embedded in DNA solutions. Surprisingly, tracer particles in the shear frame exhibit transient superdiffusivity and strong dynamic heterogeneity. The probability distribution functions of particle displacements follow a power-law scaling at large displacements, indicating a Lévy-walk-type motion, reminiscent of tracer dynamics in entangled wormlike micelle solutions and sheared colloidal glasses. We further characterize the length and time scales associated with the abnormal dynamics of tracer particles. We hypothesize that the unusual particle dynamics arise from localized shear-induced chain disentanglement.

Developing Structure-Property Relationships in Branched Wormlike Micelles via Advanced Rheological and Neutron Scattering Techniques

NASA Astrophysics Data System (ADS)

Calabrese, Michelle A.

Surfactant wormlike micelles (WLMs) are of particular scientific interest due to their ability to branch, break, and reform under shear, which can lead to shear banding flow instabilities. The tunable self-assembly of WLMs makes them ubiquitous in applications ranging from consumer products to energy recovery fluids. Altering the topology of WLMs by inducing branching provides a microstructural pathway to design and optimize the flow properties for such targeted applications. The goal of this thesis is to understand the role of micellar branching on the resulting equilibrium and non-equilibrium properties, while advancing instrumentation and analysis methods in rheology and neutron scattering. The degree of branching in the mixed cationic/anionic surfactant solutions is controlled by the addition of sodium tosylate. The equilibrium properties are characterized via small angle neutron scattering (SANS), linear viscoelastic rheology, neutron spin echo, and dynamic light scattering. Combining rheology with spatiotemporally-resolved SANS enables unambiguous identification of non-equilibrium rheological and scattering signatures of branching and shear banding. The nonlinear WLM response is characterized via flow-SANS under steady shear, shear startup, and large amplitude oscillatory shear. New methods of time-resolved data analysis are developed, which improve experimental resolution by several-fold. Shear-induced orientation is a complex function of branching level, radial position, and deformation type. The structural mechanisms behind shear band formation are elucidated for steady and dynamic flows, which depend on branching level. Shear banding disappears at high branching levels for all deformation types. These responses are used to validate constitutive modeling predictions of dynamic shear banding for the first time. Finally, quantitative metrics to predict shear banding from rheology or flow-induced orientation are developed. Together, advanced rheological and neutron techniques provide a platform for creating structure-property relationships that predict flow and structural phenomena in WLMs and other soft materials. These methods have enabled characteristic differences in linear versus branched WLMs to be determined. This research is part of a broader effort to characterize branching in polymers and self-assembled systems, and may aid in the formulation of WLMs for specific applications. Finally, this work provides a basis for testing and developing microstructure-based constitutive equations that incorporate micellar breakage and branching.

Microstructural evolution of a model, shear-banding micellar solution during shear startup and cessation.

PubMed

López-Barrón, Carlos R; Gurnon, A Kate; Eberle, Aaron P R; Porcar, Lionel; Wagner, Norman J

2014-04-01

We present direct measurements of the evolution of the segmental-level microstructure of a stable shear-banding polymerlike micelle solution during flow startup and cessation in the plane of flow. These measurements provide a definitive, quantitative microstructural understanding of the stages observed during flow startup: an initial elastic response with limited alignment that yields with a large stress overshoot to a homogeneous flow with associated micellar alignment that persists for approximately three relaxation times. This transient is followed by a shear (kink) band formation with a flow-aligned low-viscosity band that exhibits shear-induced concentration fluctuations and coexists with a nearly isotropic band of homogenous, highly viscoelastic micellar solution. Stable, steady banding flow is achieved only after approximately two reptation times. Flow cessation from this shear-banded state is also found to be nontrivial, exhibiting an initial fast relaxation with only minor structural relaxation, followed by a slower relaxation of the aligned micellar fluid with the equilibrium fluid's characteristic relaxation time. These measurements resolve a controversy in the literature surrounding the mechanism of shear banding in entangled wormlike micelles and, by means of comparison to existing literature, provide further insights into the mechanisms driving shear-banding instabilities in related systems. The methods and instrumentation described should find broad use in exploring complex fluid rheology and testing microstructure-based constitutive equations.

Multivariate Analysis of Mixed Lipid Aggregate Phase Transitions Monitored Using Raman Spectroscopy.

PubMed

Neal, Sharon L

2018-01-01

The phase behavior of aqueous 1,2-dimyristoyl-sn-glycero-3-phosphorylcholine (DMPC)/1,2-dihexanoyl-sn-glycero-3-phosphocholine (DHPC) mixtures between 8.0 ℃ and 41.0 ℃ were monitored using Raman spectroscopy. Temperature-dependent Raman matrices were assembled from series of spectra and subjected to multivariate analysis. The consensus of pseudo-rank estimation results is that seven to eight components account for the temperature-dependent changes observed in the spectra. The spectra and temperature response profiles of the mixture components were resolved by applying a variant of the non-negative matrix factorization (NMF) algorithm described by Lee and Seung (1999). The rotational ambiguity of the data matrix was reduced by augmenting the original temperature-dependent spectral matrix with its cumulative counterpart, i.e., the matrix formed by successive integration of the spectra across the temperature index (columns). Successive rounds of constrained NMF were used to isolate component spectra from a significant fluorescence background. Five major components exhibiting varying degrees of gel and liquid crystalline lipid character were resolved. Hydrogen-bonded water networks exhibiting varying degrees of organization are associated with the lipid components. Spectral parameters were computed to compare the chain conformation, packing, and hydration indicated by the resolved spectra. Based on spectral features and relative amounts of the components observed, four components reflect long chain lipid response. The fifth component could reflect the response of the short chain lipid, DHPC, but there were no definitive spectral features confirming this assignment. A minor component of uncertain assignment that exhibits a striking response to the DMPC pre-transition and chain melting transition also was recovered. While none of the spectra resolved exhibit features unequivocally attributable to a specific aggregate morphology or step in the gelation process, the results are consistent with the evolution of mixed phase bicelles (nanodisks) and small amounts of worm-like DMPC/DHPC aggregates, and perhaps DHPC micelles, at low temperature to suspensions of branched and entangled worm-like aggregates above the DMPC gel phase transition and perforated multi-lamellar aggregates at high temperature.

Curcumin-Loading-Dependent Stability of PEGMEMA-Based Micelles Affects Endocytosis and Exocytosis in Colon Carcinoma Cells.

PubMed

Chang, Teddy; Trench, David; Putnam, Joshua; Stenzel, Martina H; Lord, Megan S

2016-03-07

Polymeric micelles were formed from poly(poly(ethylene glycol) methyl ether methacrylate)-block-poly(styrene) (P(PEGMEMA)-b-PS) block copolymer of two different chain lengths. The micelles formed were approximately 16 and 46 nm in diameter and used to encapsulate curcumin. Upon loading of the curcumin into the micelles, their size increased to approximately 34 and 80 nm in diameter, respectively, with a loading efficiency of 58%. The unloaded micelles were not cytotoxic to human colon carcinoma cells, whereas only the smaller loaded micelles were cytotoxic after 72 h of exposure. The micelles were rapidly internalized by the cells within minutes of exposure, with the loaded micelles internalized to a greater extent owing to their enhanced stability compared to that of the unloaded micelles. The larger micelles were more rapidly internalized and exocytosed than the smaller micelles, demonstrating the effect of micelle size and drug loading on drug delivery and cytotoxicity.

The role of non-covalent interactions in anticancer drug loading and kinetic stability of polymeric micelles.

PubMed

Yang, Chuan; Attia, Amalina B Ebrahim; Tan, Jeremy P K; Ke, Xiyu; Gao, Shujun; Hedrick, James L; Yang, Yi-Yan

2012-04-01

A new series of acid- and urea-functionalized polycarbonate block copolymers were synthesized via organocatalytic living ring-opening polymerization using methoxy poly(ethylene glycol) (PEG) as a macroinitiator to form micelles as drug delivery carriers. The micelles were characterized for critical micelle concentration, particle size and size distribution, kinetic stability and loading capacity for a model anticancer drug, doxorubicin (DOX) having an amine group. The acid/urea groups were placed in block forms (i.e. acid as the middle block or the end block) or randomly distributed in the polycarbonate block to investigate molecular structure effect. The micelles formed from the polymers in both random and block forms provided high drug loading capacity due to strong ionic interaction between the acid in the polymer and the amine in DOX. However, the polymers with acid and urea groups placed in the block forms formed micelles with wider size distribution (two size populations), and their DOX-loaded micelles were less stable. The number of acid/urea groups in the random form was further varied from 5 to 8, 13 and 19 to study its effects on self-assembly behaviors and DOX loading. An increased number of acid/urea groups yielded DOX-loaded micelles with smaller size and enhanced kinetic stability because of improved inter-molecular polycarbonate-polycarbonate (urea-urea and urea-acid) hydrogen-bonding and polycarbonate-DOX (acid-amine) ionic interactions. However, when the number of acid/urea groups was 13 or higher, micelles aggregated in a serum-containing medium, and freeze-dried DOX-loaded micelles were unable to re-disperse in an aqueous solution. Among all the polymers synthesized in this study, 1b with 8 acid/urea groups in the random form had the optimum properties. In vitro release studies showed that DOX release from 1b micelles was sustained over 7 h without significant initial burst release. MTT assays demonstrated that the polymer was not toxic towards HepG2 and HEK293 cells. Importantly, DOX-loaded micelles were potent against HepG2 cells with IC(50) of 0.26 mg/L, comparable to that of free DOX (IC(50): 0.20 mg/L). In addition, DOX-loaded 1b micelles yielded lower DOX content in the heart tissue of the tested mice as compared to free DOX formulation after i.v. injection. These findings signify that 1b micelles may be a promising carrier for delivery of anticancer drugs that contain amine groups. Copyright © 2011 Elsevier Ltd. All rights reserved.

Method for forming thermally stable nanoparticles on supports

DOEpatents

Roldan Cuenya, Beatriz; Naitabdi, Ahmed R.; Behafarid, Farzad

2013-08-20

An inverse micelle-based method for forming nanoparticles on supports includes dissolving a polymeric material in a solvent to provide a micelle solution. A nanoparticle source is dissolved in the micelle solution. A plurality of micelles having a nanoparticle in their core and an outer polymeric coating layer are formed in the micelle solution. The micelles are applied to a support. The polymeric coating layer is then removed from the micelles to expose the nanoparticles. A supported catalyst includes a nanocrystalline powder, thin film, or single crystal support. Metal nanoparticles having a median size from 0.5 nm to 25 nm, a size distribution having a standard deviation .ltoreq.0.1 of their median size are on or embedded in the support. The plurality of metal nanoparticles are dispersed and in a periodic arrangement. The metal nanoparticles maintain their periodic arrangement and size distribution following heat treatments of at least 1,000.degree. C.

Process of forming compounds using reverse micelle or reverse microemulsion systems

DOEpatents

Linehan, John C.; Fulton, John L.; Bean, Roger M.

1998-01-01

The present invention is directed to a process for producing a nanometer-sized metal compound. The process comprises forming a reverse micelle or reverse microemulsion system comprising a polar fluid in a non-polar or low-polarity fluid. A first reactant comprising a multi-component, water-soluble metal compound is introduced into the polar fluid in a non-polar or low-polarity fluid. This first reactant can be introduced into the reverse micelle or reverse microemulsion system during formation thereof or subsequent to the formation of the reverse micelle or microemulsion system. The water-soluble metal compound is then reacted in the reverse micelle or reverse microemulsion system to form the nanometer-sized metal compound. The nanometer-sized metal compound is then precipitated from the reverse micelle or reverse microemulsion system.

Small angle neutron scattering (SANS) study of gastric mucin solutions

NASA Astrophysics Data System (ADS)

Hong, Z.; Bansil, R.; Waigh, T.; Turner, B.; Bhaskar, K. R.; Afdhal, N.; Lal, J.

2002-03-01

We report the first results from a SANS study of purified porcine gastric mucin solutions in D2O. The ability of this glycoprotein to protect the stomach epithelium from acid damage, may be due to a pH dependent conformational transition which leads to gelation at low pH Cao et. al. (Biophysical. J. 76, 1250, 1999). SANS measurements were made over the concentration range of 1 -15 mg/ml at pH 7, 4 and 2. The data indicate that at pH 7 the excluded volume exponent is 1.7, characteristic of swollen chains whereas at pH 2 this exponent increases to 2, indicating theta or poor solvent conditions, consistent with the hydrophobic interactions increasing at lower pH. From a Guinier analysis of the 1mg/ml data at low q's (0.003- 0.007 Å-1) we estimate the cross section radius of the effective cylinder to be 23nm and its length as 96nm in an unbuffered sample, i.e. close to pH 7. In the intermediate q-range (0.01 -0.1Å-1) at pH 7 a fit to the Debye chain gives radius of gyration Rg of 16nm. Mucin is best modelled as an elongated micelle with a cylindrical or worm-like chain to represent the protein core and the sugar chains forming the corona. Results of such calculations will be presented.

Chemical reactions in reverse micelle systems

DOEpatents

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

1993-08-24

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.

Bending elasticity of macromolecules: analytic predictions from the wormlike chain model.

PubMed

Polley, Anirban; Samuel, Joseph; Sinha, Supurna

2013-01-01

We present a study of the bend angle distribution of semiflexible polymers of short and intermediate lengths within the wormlike chain model. This enables us to calculate the elastic response of a stiff molecule to a bending moment. Our results go beyond the Hookean regime and explore the nonlinear elastic behavior of a single molecule. We present analytical formulas for the bend angle distribution and for the moment-angle relation. Our analytical study is compared against numerical Monte Carlo simulations. The functional forms derived here can be applied to fluorescence microscopic studies on actin and DNA. Our results are relevant to recent studies of "kinks" and cyclization in short and intermediate length DNA strands.

Complex and hierarchical micelle architectures from diblock copolymers using living, crystallization-driven polymerizations.

PubMed

Gädt, Torben; Ieong, Nga Sze; Cambridge, Graeme; Winnik, Mitchell A; Manners, Ian

2009-02-01

Block copolymers consist of two or more chemically distinct polymer segments, or blocks, connected by a covalent link. In a selective solvent for one of the blocks, core-corona micelle structures are formed. We demonstrate that living polymerizations driven by the epitaxial crystallization of a core-forming metalloblock represent a synthetic tool that can be used to generate complex and hierarchical micelle architectures from diblock copolymers. The use of platelet micelles as initiators enables the formation of scarf-like architectures in which cylindrical micelle tassels of controlled length are grown from specific crystal faces. A similar process enables the fabrication of brushes of cylindrical micelles on a crystalline homopolymer substrate. Living polymerizations driven by heteroepitaxial growth can also be accomplished and are illustrated by the formation of tri- and pentablock and scarf architectures with cylinder-cylinder and platelet-cylinder connections, respectively, that involve different core-forming metalloblocks.

Filamentous, mixed micelles of triblock copolymers enhance tumor localization of indocyanine green in a murine xenograft model

PubMed Central

Kim, Tae Hee; Mount, Christopher W; Dulken, Benjamin W; Ramos, Jenelyn; Fu, Caroline J; Khant, Htet A; Chiu, Wah; Gombotz, Wayne R; Pun, Suzie H

2012-01-01

Polymeric micelles formed by the self-assembly of amphiphilic block copolymers can be used to encapsulate hydrophobic drugs for tumor-delivery applications. Filamentous carriers with high aspect ratios offer potential advantages over spherical carriers, including prolonged circulation times. In this work, mixed micelles comprised of poly (ethylene oxide)-poly-[(R)-3-hydroxybutyrate]-poly (ethylene oxide) (PEO-PHB-PEO) and Pluronic F-127 (PF-127) were used to encapsulate a near-infrared fluorophore. The micelle formulations were assessed for tumor accumulation after tail vein injection to xenograft tumor-bearing mice by non-invasive optical imaging. The mixed micelle formulation that facilitated the highest tumor accumulation was shown by cryo-electron microscopy to be filamentous in structure compared to spherical structures of pure PF-127 micelles. In addition, increased dye loading efficiency and dye stability was attained in this mixed micelle formulation compared to pure PEO-PHB-PEO micelles. Therefore, the optimized PEO-PHB-PEO/PF-127 mixed micelle formulation offers advantages for cancer delivery over micelles formed from the individual copolymer components. PMID:22118658

Musk Oxen and Micelles

NASA Astrophysics Data System (ADS)

Hill, John W.

1996-09-01

Musk oxen behavior provides an analogy to micelle formation by amphipathic substances. Mature male musk oxen protect their young and females from wolves by forming a protective circle around them. The males stand with their tails to the inside and their heads facing outward. Amphipathic substances such as soap form micelles. The hydrophobic hydrocarbon tails of the soap are turned to the inside of the micelle and the hydrophilic carboxylate heads are on the outside at the interface with the polar water molecules.

Insights into intermediate phases of human intestinal fluids visualized by atomic force microscopy and cryo-transmission electron microscopy ex vivo.

PubMed

Müllertz, Anette; Fatouros, Dimitrios G; Smith, James R; Vertzoni, Maria; Reppas, Christos

2012-02-06

The current work aims to study at the ultrastructural level the morphological development of colloidal intermediate phases of human intestinal fluids (HIFs) produced during lipid digestion. HIFs were aspirated near the ligament of Treitz early (30 min), Aspirate(early), and 1 h, Aspirate(1h)(ave,comp), after the administration of a heterogeneous liquid meal into the antrum. The composition of the sample aspirated 1 h after meal administration was similar to the average lumenal composition 1 h after meal administration (Aspirate(1h)(ave,comp)). The colloidal structures of individual aspirates and supernatants of aspirates after ultracentrifugation (micellar phase) were characterized by means of atomic force microscopy (AFM) and cryogenic transmission electron microscopy (Cryo-TEM). AFM revealed domain-like structures in Aspirate(early) and both vesicles and large aggregates Aspirate(1h)(ave,comp). Rough surfaces and domains varying in size were frequently present in the micellar phase of both Aspirate(early) and Aspirate(1h)(ave,comp). Cryo-TEM revealed an abundance of spherical micelles and occasionally presented worm-like micelles coexisting with faceted and less defined vesicles in Aspirate(early) and Aspirate(1h)(ave,comp). In Aspirate(1h)(ave,comp) oil droplets were visualized with bilayers closely located to their surface suggesting lipolytic product phases accumulated on the surface of the oil droplet. In the micellar phase of Aspirate(early), Cryo-TEM revealed the presence of spherical micelles, small vesicles, membrane fragments, oil droplets and plate-like structures. In the micellar phase of Aspirate(1h)(ave,comp) the only difference was the absence of oil droplets. Visualization studies previously performed with biorelevant media revealed structural features with many similarities as presented in the current investigation. The impression of the complexity and diversion of these phases has been reinforced with the excessive variation of structural features visualized ex vivo in the current study offering insights at the ultrastuctural level of intermediate phases which impact drug solubilization.

Influence of phosphocholine alkyl chain length on peptide-micelle interactions and micellar size and shape.

PubMed

Göbl, Christoph; Dulle, Martin; Hohlweg, Walter; Grossauer, Jörg; Falsone, S Fabio; Glatter, Otto; Zangger, Klaus

2010-04-08

The interaction with biological membranes is of functional importance for many peptides and proteins. Structural studies on such membrane-bound biomacromolecules are often carried out in solutions containing small membrane-mimetic assemblies of detergent molecules. To investigate the influence of the hydrophobic chain length on the structure, diffusional and dynamical behavior of a peptide bound to micelles, we studied the binding of three peptides to n-phosphocholines with n ranging from 8 to 16. The peptides studied are the 15 residue antimicrobial peptide CM15, the 25-residue transmembrane helix 7 of yeast V-ATPase (TM7), and the 35-residue bacterial toxin LdrD. To keep the dimension of the peptide-membrane-mimetic assembly small, micelles are typically used when studying membrane-bound peptides and proteins, for example, by solution NMR spectroscopy. Since they are readily available in deuterated form most often sodium-dodecylsulfate (SDS) and dodecylphosphocholine (DPC) are used as the micelle-forming detergent. Using NMR, CD, and SAXS, we found that all phosphocholines studied form spherical micelles in the presence and absence of small bound peptides and the diameters of the micelles are basically unchanged upon peptide binding. The size of the peptide relative to the micelle determines to what extent the secondary structure can form. For small peptides (up to approximately 25 residues) the use of shorter chain phosphocholines is recommended for solution NMR studies due to the favorable spectral quality and since they are as well-structured as in DPC. In contrast, larger peptides are better structured in micelles formed by detergents with chain lengths longer than DPC.

Thermally stable nanoparticles on supports

DOEpatents

Roldan Cuenya, Beatriz; Naitabdi, Ahmed R.; Behafarid, Farzad

2012-11-13

An inverse micelle-based method for forming nanoparticles on supports includes dissolving a polymeric material in a solvent to provide a micelle solution. A nanoparticle source is dissolved in the micelle solution. A plurality of micelles having a nanoparticle in their core and an outer polymeric coating layer are formed in the micelle solution. The micelles are applied to a support. The polymeric coating layer is then removed from the micelles to expose the nanoparticles. A supported catalyst includes a nanocrystalline powder, thin film, or single crystal support. Metal nanoparticles having a median size from 0.5 nm to 25 nm, a size distribution having a standard deviation .ltoreq.0.1 of their median size are on or embedded in the support. The plurality of metal nanoparticles are dispersed and in a periodic arrangement. The metal nanoparticles maintain their periodic arrangement and size distribution following heat treatments of at least 1,000.degree. C.

Identification and Analysis of Partial Shading Breakdown Sites in CuIn xGa (1-x)Se 2 Modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palmiotti, Elizabeth; Johnston, Steven; Gerber, Andreas

In this paper, CuIn xGa (1-x) (CIGS) mini-modules are stressed under reverse bias, resembling partial shading conditions, to predict and characterize where failures occur. Partial shading can cause permanent damage in the form of 'wormlike' defects on thin-film modules due to thermal runaway. This results in module-scale power losses. We have used dark lock-in thermography (DLIT) to spatially observe localized heating when reverse-bias breakdown occurs on various CIGS mini-modules. For better understanding of how and where these defects originated and propagated, we have developed techniques where the current is limited during reverse-bias stressing. This allows for DLIT-based detection and detailedmore » studying of the region where breakdown is initiated before thermal runaway leads to permanent damage. Statistics of breakdown sites using current-limited conditions has allowed for reasonable identification of the as-grown defects where permanent breakdown will likely originate. Scanning electron microscope results and wormlike defect analysis show that breakdown originates in defects such as small pits, craters, or cracks in the CIGS layer, and the wormlike defects propagate near the top CIGS interface.« less

Identification and Analysis of Partial Shading Breakdown Sites in CuIn xGa (1-x)Se 2 Modules

DOE PAGES

Palmiotti, Elizabeth; Johnston, Steven; Gerber, Andreas; ...

2017-12-20

In this paper, CuIn xGa (1-x) (CIGS) mini-modules are stressed under reverse bias, resembling partial shading conditions, to predict and characterize where failures occur. Partial shading can cause permanent damage in the form of 'wormlike' defects on thin-film modules due to thermal runaway. This results in module-scale power losses. We have used dark lock-in thermography (DLIT) to spatially observe localized heating when reverse-bias breakdown occurs on various CIGS mini-modules. For better understanding of how and where these defects originated and propagated, we have developed techniques where the current is limited during reverse-bias stressing. This allows for DLIT-based detection and detailedmore » studying of the region where breakdown is initiated before thermal runaway leads to permanent damage. Statistics of breakdown sites using current-limited conditions has allowed for reasonable identification of the as-grown defects where permanent breakdown will likely originate. Scanning electron microscope results and wormlike defect analysis show that breakdown originates in defects such as small pits, craters, or cracks in the CIGS layer, and the wormlike defects propagate near the top CIGS interface.« less

"Non-equilibrium" block copolymer micelles with glassy cores: a predictive approach based on theory of equilibrium micelles.

PubMed

Nagarajan, Ramanathan

2015-07-01

Micelles generated in water from most amphiphilic block copolymers are widely recognized to be non-equilibrium structures. Typically, the micelles are prepared by a kinetic process, first allowing molecular scale dissolution of the block copolymer in a common solvent that likes both the blocks and then gradually replacing the common solvent by water to promote the hydrophobic blocks to aggregate and create the micelles. The non-equilibrium nature of the micelle originates from the fact that dynamic exchange between the block copolymer molecules in the micelle and the singly dispersed block copolymer molecules in water is suppressed, because of the glassy nature of the core forming polymer block and/or its very large hydrophobicity. Although most amphiphilic block copolymers generate such non-equilibrium micelles, no theoretical approach to a priori predict the micelle characteristics currently exists. In this work, we propose a predictive approach for non-equilibrium micelles with glassy cores by applying the equilibrium theory of micelles in two steps. In the first, we calculate the properties of micelles formed in the mixed solvent while true equilibrium prevails, until the micelle core becomes glassy. In the second step, we freeze the micelle aggregation number at this glassy state and calculate the corona dimension from the equilibrium theory of micelles. The condition when the micelle core becomes glassy is independently determined from a statistical thermodynamic treatment of diluent effect on polymer glass transition temperature. The predictions based on this "non-equilibrium" model compare reasonably well with experimental data for polystyrene-polyethylene oxide diblock copolymer, which is the most extensively studied system in the literature. In contrast, the application of the equilibrium model to describe such a system significantly overpredicts the micelle core and corona dimensions and the aggregation number. The non-equilibrium model suggests ways to obtain different micelle sizes for the same block copolymer, by the choices we can make of the common solvent and the mode of solvent substitution. Published by Elsevier Inc.

Mixed micellization between natural and synthetic block copolymers: β-casein and Lutrol F-127.

PubMed

Portnaya, Irina; Khalfin, Rafail; Kesselman, Ellina; Ramon, Ory; Cogan, Uri; Danino, Dganit

2011-02-28

Amphiphilic block copolymers and mixtures of amphiphiles find broad applications in numerous technologies, including pharma, food, cosmetic and detergency. Here we report on the interactions between a biological charged diblock copolymer, β-casein, and a synthetic uncharged triblock copolymer, Lutrol F-127 (EO(101)PO(56)EO(101)), on their mixed micellization characteristics and the micelles' structure and morphology. Isothermal titration calorimetry (ITC) experiments indicate that mixed micelles form when Lutrol is added to monomeric as well as to assembled β-casein. The main driving force for the mixed micellization is the hydrophobic interactions. Above β-casein CMC, strong perturbations caused by penetration of the hydrophobic oxypropylene sections of Lutrol into the protein micellar core lead to disintegration of the micelles and reformation of mixed Lutrol/β-casein micelles. The negative enthalpy of micelle formation (ΔH) and cooperativity increase with raising β-casein concentration in solution. ζ-potential measurements show that Lutrol interacts with the protein micelles to form mixed micelles even below its critical micellization temperature (CMT). They further indicate that Lutrol effectively masks the protein charges, probably by forming a coating layer of the ethyleneoxide rich chains. Small-angle X-ray scattering (SAXS) and cryogenic-transmission electron microscopy (cryo-TEM) indicate relatively small changes in the oblate micellar shape, but do show swelling along the small axis of β-casein micelles in the presence of Lutrol, thereby confirming the formation of mixed micelles.

A Novel Solubility-Enhanced Rubusoside-Based Micelles for Increased Cancer Therapy

NASA Astrophysics Data System (ADS)

Zhang, Meiying; Dai, Tongcheng; Feng, Nianping

2017-04-01

Many anti-cancer drugs have a common problem of poor solubility. Increasing the solubility of the drugs is very important for its clinical applications. In the present study, we revealed that the solubility of insoluble drugs was significantly enhanced by adding rubusoside (RUB). Further, it was demonstrated that RUB could form micelles, which was well characterized by Langmuir monolayer investigation, transmission electron microscopy, atomic-force microscopy, and cryogenic transmission electron microscopy. The RUB micelles were ellipsoid with the horizontal distance of 25 nm and vertical distance of 1.2 nm. Insoluble synergistic anti-cancer drugs including curcumin and resveratrol were loaded in RUB to form anti-cancer micelles RUB/CUR + RES. MTT assay showed that RUB/CUR + RES micelles had more significant toxicity on MCF-7 cells compared to RUB/CUR micelles + RUB/RES micelles. More importantly, it was confirmed that RUB could load other two insoluble drugs together for remarkably enhanced anti-cancer effect compared to that of RUB/one drug + RUB/another drug. Overall, we concluded that RUB-based micelles could efficiently load insoluble drugs for enhanced anti-cancer effect.

Structural changes in block copolymer micelles induced by cosolvent mixtures†

PubMed Central

Kelley, Elizabeth G.; Smart, Thomas P.; Jackson, Andrew J.; Sullivan, Millicent O.

2013-01-01

We investigated the influence of tetrahydrofuran (THF) addition on the structure of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution. Our studies showed that while the micelles remained starlike, the micelle core-corona interfacial tension and micelle size decreased upon THF addition. The detailed effects of the reduction in interfacial tension were probed using contrast variations in small angle neutron scattering (SANS) experiments. At low THF contents (high interfacial tensions), the SANS data were fit to a micelle form factor that incorporated a radial density distribution of corona chains to account for the starlike micelle profile. However, at higher THF contents (low interfacial tensions), the presence of free chains in solution affected the scattering at high q and required the implementation of a linear combination of micelle and Gaussian coil form factors. These SANS data fits indicated that the reduction in interfacial tension led to broadening of the core-corona interface, which increased the PB chain solvent accessibility at intermediate THF solvent fractions. We also noted that the micelle cores swelled with increasing THF addition, suggesting that previous assumptions of the micelle core solvent content in cosolvent mixtures may not be accurate. Control over the size, corona thickness, and extent of solvent accessible PB in these micelles can be a powerful tool in the development of targeting delivery vehicles. PMID:24282441

Structural changes in block copolymer micelles induced by cosolvent mixtures

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelley, Elizabeth G.; Smart, Thomas P.; Jackson, Andrew J.

2012-11-26

We investigated the influence of tetrahydrofuran (THF) addition on the structure of poly(1,2-butadiene-b-ethylene oxide) [PB-PEO] micelles in aqueous solution. Our studies showed that while the micelles remained starlike, the micelle core-corona interfacial tension and micelle size decreased upon THF addition. The detailed effects of the reduction in interfacial tension were probed using contrast variations in small angle neutron scattering (SANS) experiments. At low THF contents (high interfacial tensions), the SANS data were fit to a micelle form factor that incorporated a radial density distribution of corona chains to account for the starlike micelle profile. However, at higher THF contents (lowmore » interfacial tensions), the presence of free chains in solution affected the scattering at high q and required the implementation of a linear combination of micelle and Gaussian coil form factors. These SANS data fits indicated that the reduction in interfacial tension led to broadening of the core-corona interface, which increased the PB chain solvent accessibility at intermediate THF solvent fractions. We also noted that the micelle cores swelled with increasing THF addition, suggesting that previous assumptions of the micelle core solvent content in cosolvent mixtures may not be accurate. Control over the size, corona thickness, and extent of solvent accessible PB in these micelles can be a powerful tool in the development of targeting delivery vehicles.« less

Spray-dried casein-based micelles as a vehicle for solubilization and controlled delivery of flutamide: formulation, characterization, and in vivo pharmacokinetics.

PubMed

Elzoghby, Ahmed O; Helmy, Maged W; Samy, Wael M; Elgindy, Nazik A

2013-08-01

Novel casein (CAS)-based micelles loaded with the poorly soluble anti-cancer drug, flutamide (FLT), were successfully developed in a powdered form via spray-drying technique. Genipin (GNP) was used to crosslink CAS micelles as demonstrated by color variation of the micelles. Drug solubilization was enhanced by incorporation within the hydrophobic micellar core which was confirmed by solubility study and UV spectra. Spherical core-shell micelles were obtained with a particle size below 100 nm and zeta potential around -30 mV. At low drug loading, FLT was totally incorporated within micellar core as revealed by thermal analysis. However, at higher loading, excess non-incorporated drug at micelle surface caused a significant reduction in the surface charge density. Turbidity measurements demonstrated the high physical stability of micelles for 2 weeks dependent on GNP-crosslinking degree. In a dry powdered form, the micelles were stable for 6 months with no significant changes in drug content or particle size. A sustained drug release from CAS micelles up to 5 days was observed. After i.v. administration into rats, CAS micelles exhibited a prolonged plasma circulation of FLT compared to drug solution. Furthermore, a more prolonged drug systemic circulation was observed for GNP-crosslinked micelles. Overall, this study reports the application of spray-dried natural protein-based micelles for i.v. delivery of hydrophobic anti-cancer drugs such as FLT. Copyright © 2013 Elsevier B.V. All rights reserved.

Targeted polymeric micelles for delivery of poorly soluble drugs.

PubMed

Torchilin, V P

2004-10-01

Polymeric micelles (micelles formed by amphiphilic block copolymers) demonstrate a series of attractive properties as drug carriers, such as high stability both in vitro and in vivo and good biocompatibility, and can be successfully used for the solubilization of various poorly soluble pharmaceuticals. These micelles can also be used as targeted drug delivery systems. The targeting can be achieved via the enhanced permeability and retention effect (into the areas with the compromised vasculature), by making micelles of stimuli-responsive amphiphilic block copolymers, or by attaching specific targeting ligand molecules to the micelle surface. Immunomicelles prepared by coupling monoclonal antibody molecules to p-nitrophenylcarbonyl groups on the water-exposed termini of the micelle corona-forming blocks demonstrate high binding specificity and targetability. Immunomicelles prepared with cancer-specific monoclonal antibody 2C5 specifically bind to different cancer cells in vitro and demonstrate increased therapeutic activity in vivo. This new family of pharmaceutical carriers can be used for the solubilization and targeted delivery of poorly soluble drugs to various pathological sites in the body.

Self-assembling semiconducting polymers--rods and gels from electronic materials.

PubMed

Clark, Andrew P-Z; Shi, Chenjun; Ng, Benny C; Wilking, James N; Ayzner, Alexander L; Stieg, Adam Z; Schwartz, Benjamin J; Mason, Thomas G; Rubin, Yves; Tolbert, Sarah H

2013-02-26

In an effort to favor the formation of straight polymer chains without crystalline grain boundaries, we have synthesized an amphiphilic conjugated polyelectrolyte, poly(fluorene-alt-thiophene) (PFT), which self-assembles in aqueous solutions to form cylindrical micelles. In contrast to many diblock copolymer assemblies, the semiconducting backbone runs parallel, not perpendicular, to the long axis of the cylindrical micelle. Solution-phase micelle formation is observed by X-ray and visible light scattering. The micelles can be cast as thin films, and the cylindrical morphology is preserved in the solid state. The effects of self-assembly are also observed through spectral shifts in optical absorption and photoluminescence. Solutions of higher-molecular-weight PFT micelles form gel networks at sufficiently high aqueous concentrations. Rheological characterization of the PFT gels reveals solid-like behavior and strain hardening below the yield point, properties similar to those found in entangled gels formed from surfactant-based micelles. Finally, electrical measurements on diode test structures indicate that, despite a complete lack of crystallinity in these self-assembled polymers, they effectively conduct electricity.

The Formation of Chimeric Nanomorphologies, as a Reflection of Naturally Occurring Thermodynamic Processes

NASA Astrophysics Data System (ADS)

Naziris, N.; Demetzos, C.

2017-11-01

The self-assembly process of different in nature biomaterials leads to the morphogenesis of various nano-structures, where the individual molecule properties (e.g. hydrophilic-to-hydrophobic balance and elasticity), profoundly affect the intermediate surfaces’ interfacial thermodynamics. Herein, the mixing of a phospholipid and an amphiphilic block copolymer, through the thin-film hydration method, gave different morphologies, among which there were vesicles (i.e. liposomes and polymersomes), micelles and worm-like structures. The formation of such variety of structures is attributed to divergent entropic pathways, which are determined by a number of parameters, such as the lipid:polymer molar ratio and the polymer composition. The developed nanosystems are considered as chimeric/mixed, because of the two different in type biomaterials that compose them. The vesicles also exhibited membrane “irregularities”, which are connected with their biophysical behavior. Nature has “chosen” vesicular forms to be the thermodynamically stable “biological apartments”, in which life was enclosed and additionally, vesicles provided compartmentalized systems, where the intracellular environment was built. Phospholipid properties result in membranes/bilayers that harmonically assimilate other molecules, like proteins and retain their integrity and functionality, while gaining additional features. A cause that alters this relationship might induce changes in the membrane composition and morphology, with respect to lipid rafts/domains, what has been linked with the activation and development of certain human disorders/diseases. The self-assembly of two different biomaterials into various structures that present distinct membrane phenomena is believed to simulate these natural processes.

Dual drug release from hydrogels covalently containing polymeric micelles that possess different drug release properties.

PubMed

Murata, Mari; Uchida, Yusuke; Takami, Taku; Ito, Tomoki; Anzai, Ryosuke; Sonotaki, Seiichi; Murakami, Yoshihiko

2017-05-01

In the present study, we designed hydrogels for dual drug release: the hydrogels that covalently contained the polymeric micelles that possess different drug release properties. The hydrogels that were formed from polymeric micelles possessing a tightly packed (i.e., well-entangled) inner core exhibited a higher storage modulus than the hydrogels that were formed from the polymeric micelles possessing a loosely packed structure. Furthermore, we conducted release experiments and fluorescent observations to evaluate the profiles depicting the release of two compounds, rhodamine B and auramine O, from either polymeric micelles or hydrogels. According to our results, (1) hydrogels that covalently contains polymeric micelles that possess different drug release properties successfully exhibit the independent release behaviors of the two compounds and (2) fluorescence microscopy can greatly facilitate efforts to evaluate drug release properties of materials. Copyright © 2017 Elsevier B.V. All rights reserved.

Passive targeting of thermosensitive diblock copolymer micelles to the lungs: synthesis and characterization of poly(N-isopropylacrylamide)-block-poly(ε-caprolactone).

PubMed

Lee, Ren-Shen; Lin, Chih-Hung; Aljuffali, Ibrahim A; Hu, Kai-Yin; Fang, Jia-You

2015-06-18

Amphiphilic poly(N-isopropylacrylamide)-block-poly(ε-caprolactone) (PNiPAAm-b-PCL) copolymers were synthesized by ring-opening polymerization to form thermosensitive micelles as nanocarriers for bioimaging and carboplatin delivery. The critical micelle concentration increased from 1.8 to 3.5 mg/l following the decrease of the PNiPAAm chain length. The copolymers revealed a lower critical solution temperature (LCST) between 33 and 40°C. The copolymers self-assembled to form spherical particles of 146-199 nm in diameter. Carboplatin in micelles exhibited a slower release at 37°C relative to that at 25°C due to the gel layer formation on the micellar shell above the LCST. The micelles containing dye or carboplatin were intravenously injected into the rats for in vivo bioimaging and drug biodistribution. The bioimaging profiles showed a significant accumulation of micelles in the lungs. The micelles could minimize the reticuloendothelial system (RES) recognition of the dye. In vivo biodistribution demonstrated an improved pulmonary accumulation of carboplatin from 2.5 to 3.4 μg/mg by the micelles as compared to the control solution. Carboplatin accumulation in the heart and kidneys was reduced after encapsulation by the micelles. This study supports the potential of PNiPAAm-b-PCL micelles to passively target the lungs and attenuate RES uptake and possible side effects.

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

PubMed

Poša, Mihalj; Tepavčević, Vesna

2011-09-01

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. Copyright © 2011 Elsevier B.V. All rights reserved.

Structure and dynamics of ionic micelles: MD simulation and neutron scattering study.

PubMed

Aoun, B; Sharma, V K; Pellegrini, E; Mitra, S; Johnson, M; Mukhopadhyay, R

2015-04-16

Fully atomistic molecular dynamics (MD) simulations have been carried out on sodium dodecyl sulfate (SDS), an anionic micelle, and three cationic (CnTAB; n = 12, 14, 16) micelles, investigating the effects of size, the form of the headgroup, and chain length. They have been used to analyze neutron scattering data. MD simulations confirm the dynamical model of global motion of the whole micelle, segmental motion (headgroup and alkyl chain), and fast torsional motion associated with the surfactants that is used to analyze the experimental data. It is found that the solvent surrounding the headgroups results in their significant mobility, which exceeds that of the tails on the nanosecond time scale. The middle of the chain is found to be least mobile, consolidating the micellar configuration. This dynamical feature is similar for all the ionic micelles investigated and therefore independent of headgroup form and charge and chain length. Diffusion constants for global and segmental motion of the different micelles are consistent with experimentally obtained values as well as known structural features. This work provides a more realistic model of micelle dynamics and offers new insight into the strongly fluctuating surface of micelles which is important in understanding micelle dispersion and related functionality, like drug delivery.

Sphere-to-rod transition of non-surface-active amphiphilic diblock copolymer micelles: a small-angle neutron scattering study.

PubMed

Kaewsaiha, Ploysai; Matsumoto, Kozo; Matsuoka, Hideki

2007-08-28

Micellization behavior of amphiphilic diblock copolymers with strong acid groups, poly(hydrogenated isoprene)-block-poly(styrenesulfonate), was investigated by small-angle neutron scattering (SANS). We have reported previously (Kaewsaiha, P.; Matsumoto, K.; Matsuoka, H. Langmuir 2005, 21, 9938) that this strongly ionic amphiphilic diblock copolymer shows almost no surface activity but forms micelles in water. In this study, the size, shape, and internal structures of the micelles formed by these unique copolymers in aqueous solution were duly investigated. The SANS data were well described by the theoretical form factor of a core-shell model and the Pedersen core-corona model. The micellar shape strongly depends on the hydrophobic chain length of the block copolymer. The polymer with the shortest hydrophobic chain was suggested to form spherical micelles, whereas the scattering curves of the longer hydrophobic chain polymers showed a q-1 dependence, reflecting the formation of rodlike micelles. Furthermore, the addition of salt at high concentration also induced the sphere-to-rod transition in micellar shape as a result of the shielding effect of electrostatic repulsion. The corona thickness was almost constant up to the critical salt concentration (around 0.2 M) and then decreased with further increases in salt concentration, which is in qualitatively agreement with existing theories. The spherical/rodlike micelle ratio was also constant up to the critical salt concentration and then decreased. The micelle size and shape of this unique polymer could be described by the common concept of the packing parameter, but the anomalously stable nature of the micelle (up to 1 M NaCl) is a special characteristic.

Synthesis of cadmium sulfide in situ in reverse micelles and in hydrocarbon gels

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petit, C.; Pileni, M.P.

1988-04-21

The synthesis in situ of cadmium sulfide semiconductors in AOT reverse micelles produces smaller and more monodispersed particles than are obtained in Triton reverse micelles or in aqueous solution. When gelatine is added to the previous solution, the semiconductor is entrapped in a hydrocarbon gel and it size remains the same as that obtained in reverse micelles. The size of the sulfite cadmium aggregate formed in AOT hydrocarbon gels is similar to that obtained under similar conditions in AOT reverse micelles. AOT surfactant can play the role of stabilizing agent. However, a more efficient stabilization is obtained by adding tomore » AOT reverse micelles another stabilizing agent such as sodium hexametaphosphate. The crystallite size is strongly dependent on the ratio of the cadmium and sulfur ions, defined by x = (Cd/sup 2 +/)/(S/sup 2 -//. The yield of reduced viologen obtained by CdS irradiation in AOT reverse micelles is 15 times more efficient than that formed in aqueous solutions whereas it is only three times more in hydrocarbon gels.« less

A symmetrical method to obtain shear moduli from microrheology.

PubMed

Nishi, Kengo; Kilfoil, Maria L; Schmidt, Christoph F; MacKintosh, F C

2018-05-16

Passive microrheology typically deduces shear elastic loss and storage moduli from displacement time series or mean-squared displacements (MSD) of thermally fluctuating probe particles in equilibrium materials. Common data analysis methods use either Kramers-Kronig (KK) transformation or functional fitting to calculate frequency-dependent loss and storage moduli. We propose a new analysis method for passive microrheology that avoids the limitations of both of these approaches. In this method, we determine both real and imaginary components of the complex, frequency-dependent response function χ(ω) = χ'(ω) + iχ''(ω) as direct integral transforms of the MSD of thermal particle motion. This procedure significantly improves the high-frequency fidelity of χ(ω) relative to the use of KK transformation, which has been shown to lead to artifacts in χ'(ω). We test our method on both model and experimental data. Experiments were performed on solutions of worm-like micelles and dilute collagen solutions. While the present method agrees well with established KK-based methods at low frequencies, we demonstrate significant improvement at high frequencies using our symmetric analysis method, up to almost the fundamental Nyquist limit.

Aggregate-mediated charge transport in ionomeric electrolytes

NASA Astrophysics Data System (ADS)

Lu, Keran; Maranas, Janna; Milner, Scott

Polymers such PEO can conduct ions, and have been studied as possible replacements for organic liquid electrolytes in rechargeable metal-ion batteries. More generally, fast room-temperature ionic conduction has been reported for a variety of materials, from liquids to crystalline solids. Unfortunately, polymer electrolytes generally have limited conductivity; these polymers are too viscous to have fast ion diffusion like liquids, and too unstructured to promote cooperative transport like crystalline solids. Ionomers are polymer electrolytes in which ionic groups are covalently bound to the polymer backbone, neutralized by free counterions. These materials also conduct ions, and can exhibit strong ionic aggregation. Using coarse-grained molecular dynamics, we explore the forces driving ionic aggregation, and describe the role ion aggregates have in mediating charge transport. The aggregates are string-like such that ions typically have two neighbors. We find ion aggregates self-assemble like worm-like micelles. Excess charge, or free ions, occasionally coordinate with aggregates and are transported along the chain in a Grotthuss-like mechanism. We propose that controlling ionomer aggregate structure through materials design can enhance cooperative ion transport.

Thermoresponsive complex amphiphilic block copolymer micelles investigated by laser light scattering.

PubMed

Zhao, Fang; Xie, Dinghai; Zhang, Guangzhao; Pispas, Stergios

2008-05-22

Poly(isoprene)-block-poly(ethylene oxide) (PI-b-PEO) diblock copolymers form micelles in water. The introduction of poly(ethylene oxide)-block-poly(propylene oxide)-block-poly(ethylene oxide) (PEO-b-PPO-b-PEO) triblock copolymer leads to the formation of mixed micelles through hydrophobic interaction. The dimension of the mixed micelles varies with the weight ratio (r) of PEO-b-PPO-b-PEO to PI-b-PEO. By use of laser light scattering, we have investigated the temperature dependence of the structural evolution of the micelles at different r. At r<10, the size of the mixed micelles decreases with temperature. At r>10, due to the excessive PEO-b-PPO-b-PEO chains in solution, as temperature increases, the mixed micelles aggregate into larger micelle clusters.

Responsive micellar films of amphiphilic block copolymer micelles: control on micelle opening and closing.

PubMed

Chen, Zhiquan; He, Changcheng; Li, Fengbin; Tong, Ling; Liao, Xingzhi; Wang, Yong

2010-06-01

We reported the deliberate control on the micelle opening and closing of amphiphilic polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) micellar films by exposing them to selective solvents. We first treated the micellar films with polar solvents including ethanol and water (pH = 4, 8, and 12) that have different affinities to P2VP. We observed opening of the micelles in all the cases. Both the size of opened pores and the opening rate are dependent on the solvency of different solvents for P2VP. We then explored the closing behavior of the opened micelles using solvents having different affinities to PS. We found that the opened micelles were recovered to their initial closed micelle forms. The recovery was accompanied by a slow micelle disassociation process which gradually reduced the micelle size. The rates of the micelle closing and disassociation are also dependent on the solvency of different solvents for PS.

Influence of chain rigidity on the conformation of model lipid membranes in the presence of cylindrical nanoparticle inclusions

NASA Astrophysics Data System (ADS)

Diloreto, Chris; Wickham, Robert

2012-02-01

We employ real-space self-consistent field theory to study the conformation of model lipid membranes in the presence of solvent and cylindrical nanoparticle inclusions (''peptides''). Whereas it is common to employ a polymeric Gaussian chain model for the lipids, here we model the lipids as persistent, worm-like chains. Our motivation is to develop a more realistic field theory to describe the action of pore-forming anti-microbial peptides that disrupt the bacterial cell membrane. We employ operator-splitting and a pseudo-spectral algorithm, using SpharmonicKit for the chain tangent degrees of freedom, to solve for the worm-like chain propagator. The peptides, modelled using a mask function, have a surface patterned with hydrophobic and hydrophillic patches, but no charge. We examine the role chain rigidity plays in the hydrophobic mismatch, the membrane-mediated interaction between two peptides, the size and structure of pores formed by peptide aggregates, and the free-energy barrier for peptide insertion into the membrane. Our results suggest that chain rigidity influences both the pore structure and the mechanism of pore formation.

The efficacy of nimodipine drug delivery using mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles.

PubMed

Huang, Shuling; Yu, Xiaohong; Yang, Linlin; Song, Fenglan; Chen, Gang; Lv, Zhufen; Li, Tiao; Chen, De; Zhu, Wanhua; Yu, Anan; Zhang, Yongming; Yang, Fan

2014-10-15

In order to develop and compare mPEG-PLA micelles and mPEG-PLA/TPGS mixed micelles, with the intention to develop a highly efficient formulation for nimodipine (NIM), NIM-loaded micelles and mixed micelles were made and their pharmacokinetics were studied. Single factor experiments and orthogonal experiments were designed to optimize the final preparation process, characterizations and drug release behaviors were studied. Pharmacokinetics of NIM micelles, NIM mixed micelles were researched and were compared to NIM solution. Micelles and mixed micelles were prepared by solvent evaporation method, with relatively high drug loading efficiency and within nano-particle size range. The CMC value of mPEG-PLA was lower than that of mPEG-PLA/TPGS. The results of FTIR and TEM confirmed the spherical core-shell structure of micelles as well as mixed micelles, and the encapsulation of NIM inside the cores. In vitro release showed that micelles and mixed micelles had sustained release effect in the forms of passive diffusion and dissolution process, respectively. Following intraperitoneal administration (5mg/kg), micelles and mixed micelles were absorbed faster than solution, and with larger MRT(0-t), smaller CLz and larger AUC(0-t) as compared to that of solution, which showed micelles and mixed micelles had higher retention, slower elimination and higher bioavailability. This experiment also showed that mixed micelles released NIM more stably than micelles. By evaluate the bioequivalence, NIM micelles and NIM mixed micelles were testified non-bioequivalent to NIM solution. Micelles and mixed micelles could sustain the NIM concentrations more efficiently in plasma as compared to solution. Mixed micelles were the best ones since they had high loading content and released more stably. Thus, apprehending micelles and mixed micelles were suited as poor aqueous solubility drug carriers, and mixed micelles were better due to their high loading content and more stable release. Copyright © 2014 Elsevier B.V. All rights reserved.

CHOBIMALT: A Cholesterol-Based Detergent†

PubMed Central

Howell, Stanley C.; Mittal, Ritesh; Huang, Lijun; Travis, Benjamin; Breyer, Richard M.; Sanders, Charles R.

2010-01-01

Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins, but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3–4μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210 ± 30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1. PMID:20919740

Mesoscale crystallization of calcium phosphate nanostructures in protein (casein) micelles

NASA Astrophysics Data System (ADS)

Thachepan, Surachai; Li, Mei; Mann, Stephen

2010-11-01

Aqueous micelles of the multi-protein calcium phosphate complex, casein, were treated at 60 °C and pH 7 over several months. Although partial dissociation of the micelles into 12 nm sized amorphous calcium phosphate (ACP)/protein nanoparticles occurred within a period of 14 days, crystallization of the ACP nanoclusters into bundles of hydroxyapatite (HAP) nanofilaments was not observed until after 12 weeks. The HAP nanofilaments were formed specifically within the partially disrupted protein micelles suggesting a micelle-mediated pathway of mesoscale crystallization. Similar experiments using ACP-containing synthetic micelles prepared from β-casein protein alone indicated that co-aligned bundles of HAP nanofilaments were produced within the protein micelle interior after 24 hours at temperatures as low as 35 °C. The presence of Mg2+ ions in the casein micelles, as well as a possible synergistic effect associated with the multi-protein nature of the native aggregates, could account for the marked inhibition in mesoscale crystallization observed in the casein micelles compared with the single-component β-casein constructs.Aqueous micelles of the multi-protein calcium phosphate complex, casein, were treated at 60 °C and pH 7 over several months. Although partial dissociation of the micelles into 12 nm sized amorphous calcium phosphate (ACP)/protein nanoparticles occurred within a period of 14 days, crystallization of the ACP nanoclusters into bundles of hydroxyapatite (HAP) nanofilaments was not observed until after 12 weeks. The HAP nanofilaments were formed specifically within the partially disrupted protein micelles suggesting a micelle-mediated pathway of mesoscale crystallization. Similar experiments using ACP-containing synthetic micelles prepared from β-casein protein alone indicated that co-aligned bundles of HAP nanofilaments were produced within the protein micelle interior after 24 hours at temperatures as low as 35 °C. The presence of Mg2+ ions in the casein micelles, as well as a possible synergistic effect associated with the multi-protein nature of the native aggregates, could account for the marked inhibition in mesoscale crystallization observed in the casein micelles compared with the single-component β-casein constructs. Electronic supplementary information (ESI) available: Particle size histograms, TEM, EDX and electron diffraction data. See DOI: 10.1039/c0nr00158a

Stimuli-sensitive polymeric micelles as anticancer drug carriers.

PubMed

Na, Kun; Sethuraman, Vijay T; Bae, You Han

2006-11-01

Amphiphilic block copolymers often form core-shell type micelles by self-organization of the blocks in an aqueous medium or under specific experimental conditions. Polymeric micelles constructed from these polymers that contain a segment whose physical or chemical properties respond to small changes in environmental conditions are collectively called 'stimuli-sensitive' micelles. This class of nano-scaled constructs has been investigated as a promising anti-cancer drug carrier because the micelles are able to utilize small environmental changes and modify drug release kinetics, biodistribution and the interactions with tissues and cells. This review summarizes the recent progress in stimuli-sensitive micelles for tumor chemotherapy, particularly for those responding to hyperthermic conditions, tumor pH and endosomal/lysosomal pH.

Self-consistent field theory and numerical scheme for calculating the phase diagram of wormlike diblock copolymers

NASA Astrophysics Data System (ADS)

Jiang, Ying; Chen, Jeff Z. Y.

2013-10-01

This paper concerns establishing a theoretical basis and numerical scheme for studying the phase behavior of AB diblock copolymers made of wormlike chains. The general idea of a self-consistent field theory is the combination of the mean-field approach together with a statistical weight that describes the configurational properties of a polymer chain. In recent years, this approach has been extensively used for structural prediction of block copolymers, based on the Gaussian-model description of a polymer chain. The wormlike-chain model has played an important role in the description of polymer systems, covering the semiflexible-to-rod crossover of the polymer properties and the highly stretching regime, which the Gaussian-chain model has difficulties to describe. Although the idea of developing a self-consistent field theory for wormlike chains could be traced back to early development in polymer physics, the solution of such a theory has been limited due to technical difficulties. In particular, a challenge has been to develop a numerical algorithm enabling the calculation of the phase diagram containing three-dimensional structures for wormlike AB diblock copolymers. This paper describes a computational algorithm that combines a number of numerical tricks, which can be used for such a calculation. A phase diagram covering major parameter areas was constructed for the wormlike-chain system and reported by us, where the ratio between the total length and the persistence length of a constituent polymer is suggested as another tuning parameter for the microphase-separated structures; all detailed technical issues are carefully addressed in the current paper.

Response of cells on surface-induced nanopatterns: fibroblasts and mesenchymal progenitor cells.

PubMed

Khor, Hwei Ling; Kuan, Yujun; Kukula, Hildegard; Tamada, Kaoru; Knoll, Wolfgang; Moeller, Martin; Hutmacher, Dietmar W

2007-05-01

Ultrathin films of a poly(styrene)-block-poly(2-vinylpyrindine) diblock copolymer (PS-b-P2VP) and poly(styrene)-block-poly(4-vinylpyrindine) diblock copolymer (PS-b-P4VP) were used to form surface-induced nanopattern (SINPAT) on mica. Surface interaction controlled microphase separation led to the formation of chemically heterogeneous surface nanopatterns on dry ultrathin films. Two distinct nanopatterned surfaces, namely, wormlike and dotlike patterns, were used to investigate the influence of topography in the nanometer range on cell adhesion, proliferation, and migration. Atomic force microscopy was used to confirm that SINPAT was stable under cell culture conditions. Fibroblasts and mesenchymal progenitor cells were cultured on the nanopatterned surfaces. Phase contrast and confocal laser microscopy showed that fibroblasts and mesenchymal progenitor cells preferred the densely spaced wormlike patterns. Atomic force microscopy showed that the cells remodelled the extracellular matrix differently as they migrate over the two distinctly different nanopatterns.

Polymer nano-particle hybrid micelles: Encapsulation of POSS into semi-fluorinated polymer micelles

NASA Astrophysics Data System (ADS)

Ratnaweera, Dilru; Perahia, Dvora; Iacono, Scott; Mabry, Joseph; Smith, Dennis

2012-02-01

Self-assembly of block copolymers in selective solvents was used to form a nanoparticle (NP)/polymer hybrid micelles. These micelles can be used as a cargo vehicle for other substances such as drug delivery, and as building blocks for polymer-nanocomposites with controlled NP distribution. Association of NPs into specific blocks of the copolymer depends on the compatibility between the NPs and the block as well as their preference to the solvent that micellization takes place. The current work introduces a small angle neutron scattering study of association of Polyhedral Oligomeric Silsesquioxane (POSS) NPs into micelles of a highly segregating random copolymer, Biphenyl Perfluorocyclobutane (BPh-PFCB), in toluene, which is a good solvent for BPh. Incompatibility between the blocks drives copolymer into micelles with PFCB in the core and BPh in swollen corona. Modification of NPs with polymer chains drives POSS cages into the micelle core and prevents the micelle dissociation at higher temperatures.

Dependence of the form factor of ganglioside micelles on a conformational change with temperature

NASA Astrophysics Data System (ADS)

Corti, Mario; Boretta, Marco; Cantù, Laura; Del Favero, Elena; Lesieur, Pierre

1996-09-01

The gangliosides GM2, GM1 and GD1b, biological amphiphiles with a double tail hydrophobic part and an oligosaccharide chain headgroup, form micelles in solution. Light scattering experiments have shown that ganglioside micelles which have gone through a temperature cycle have a smaller molecular mass and hydrodynamic radius than those which have been kept at room temperature. This fact has been interpreted with the hypothesis that, with temperature, the ganglioside molecules undergo a conformational change which affects their micellar properties appreciably. Careful small angle X-ray experiments, aimed to confirm the light scattering data and to evidence differences in the micellar internal structure are presented. Ganglioside micelles are quite inhomogeneous particles with respect to X-ray scattering, since there is a large contrast variation between the inner lipid part and the external hydrated sugar layer. Experimental form factors are fitted with a double-shell oblate-ellipsoid model.

Charged triblock copolymer self-assembly into charged micelles

NASA Astrophysics Data System (ADS)

Chen, Yingchao; Zhang, Ke; Zhu, Jiahua; Wooley, Karen; Pochan, Darrin; Department of Material Science; Engineering University of Delaware Team; Department of Chemistry Texas A&M University Collaboration

2011-03-01

Micelles were formed through the self-assembly of amphiphlic block copolymer poly(acrylic acid)-block-poly(methyl acrylate)-block-polystyrene (PAA-PMA-PS). ~Importantly, the polymer is complexed with diamine molecules in pure THF solution prior to water titration solvent processing-a critical aspect in the control of final micelle geometry. The addition of diamine triggers acid-base complexation ~between the carboxylic acid PAA side chains and amines. ~Remarkably uniform spheres were found to form close-packed patterns when forced into dried films and thin, solvated films when an excess of amine was used in the polymer assembly process. Surface properties and structural features of these hexagonal-packed spherical micelles with charged corona have been explored by various characterization methods including Transmission Electron Microscopy (TEM), cryogenic TEM, z-potential analysis and Dynamic Light Scattering. The forming mechanism for this pattern and morphology changes against external stimulate such as salt will be discussed.

Mesoscale crystallization of calcium phosphate nanostructures in protein (casein) micelles.

PubMed

Thachepan, Surachai; Li, Mei; Mann, Stephen

2010-11-01

Aqueous micelles of the multi-protein calcium phosphate complex, casein, were treated at 60°C and pH 7 over several months. Although partial dissociation of the micelles into 12 nm sized amorphous calcium phosphate (ACP)/protein nanoparticles occurred within a period of 14 days, crystallization of the ACP nanoclusters into bundles of hydroxyapatite (HAP) nanofilaments was not observed until after 12 weeks. The HAP nanofilaments were formed specifically within the partially disrupted protein micelles suggesting a micelle-mediated pathway of mesoscale crystallization. Similar experiments using ACP-containing synthetic micelles prepared from ß-casein protein alone indicated that co-aligned bundles of HAP nanofilaments were produced within the protein micelle interior after 24 hours at temperatures as low as 35°C. The presence of Mg²(+) ions in the casein micelles, as well as a possible synergistic effect associated with the multi-protein nature of the native aggregates, could account for the marked inhibition in mesoscale crystallization observed in the casein micelles compared with the single-component b-casein constructs.

Structural changes of deposited casein micelles induced by membrane filtration.

PubMed

Gebhardt, R; Steinhauer, T; Meyer, P; Sterr, J; Perlich, J; Kulozik, U

2012-01-01

Casein micelles undergo shape changes when subjected to frontal filtration forces. Grazing incidence small angle X-ray scattering (GISAXS) and atomic force microscopy (AFM) allow a quantification of such structural changes on filtration cakes deposited on smooth silicon micro-sieves. A trans-membrane pressure of deltap = 400 mbar across the micro-sieve leads to an immediate film formation after deposition of casein solution. We observe significant changes in the GISAXS pattern depending on how many layers are stacked on top of each other. Compared to a deposit formed by one layer, GISAXS on a deposit formed by three layers of casein micelles leads to less scattering in the vertical and more scattering in the horizontal direction. Simulations show that the experimental results can be interpreted by a structural transformation from an originally spherical micelle shape to an ellipsoidal-deformed shape. The results are supported by AFM measurements showing a reduced lateral size of casein micelles deposited on top of a membrane pore. The observed shape changes could be due to filtration forces acting on densely packed deposits confining the micelles into ellipsoidal shapes.

Light Scattering Characterization of Elastin-Like Polypeptide Trimer Micelles

NASA Astrophysics Data System (ADS)

Tsuper, Ilona; Terrano, Daniel; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

The elastin-like polypeptides (ELP) nanoparticles are composed of three-armed star polypeptides connected by a negatively charged foldon. Each of the three arms extending from the foldon domain includes 20 repeats of the (GVGVP) amino acid sequence. The ELP polymer chains are soluble at room temperature and become insoluble at the transition temperature (close to 50 ° C), forming micelles. The size and shape of the micelle are dependent on the temperature and the pH of the solution, and on the concentration of the phosphate buffered saline (PBS). The depolarized dynamic light scattering (DDLS) was employed to study the structure and dynamics of micelles at 62 ° C. The solution was maintained at an approximate pH level of 7.3 - 7.5, while varying PBS concentration. At low salt concentrations (<15 mM), the micelle radius was about 10nm but not very reproducible on account of unstable pH levels arising from low buffer concentrations. At intermediate salt concentrations (15 - 60 mM), the system formed spherically-shaped micelles, exhibiting a steady growth in the hydrodynamic radius (Rh) from 10 to 21 nm, with increasing PBS concentration. Interestingly, higher salt concentrations (>60 mM) displayed an apparent elongation of the micelles evident by a significant VH signal, along with a surge in the apparent Rh. A model of micelle growth (and potential elongation) with increase in salt concentration is considered.

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

PubMed

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

2010-12-01

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. Copyright © 2010 Biophysical Society. Published by Elsevier Inc. All rights reserved.

How to Squeeze a Sponge: Casein Micelles under Osmotic Stress, a SAXS Study

PubMed Central

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

2010-01-01

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. PMID:21112300

Study of the interaction of potassium ion channel protein with micelle by molecular dynamics simulation

NASA Astrophysics Data System (ADS)

Shantappa, Anil; Talukdar, Keka

2018-04-01

Ion channels are proteins forming pore inside the body of all living organisms. This potassium ion channel known as KcsA channel and it is found in the each cell and nervous system. Flow of various ions is regulated by the function of the ion channels. The nerve ion channel protein with protein data bank entry 1BL8, which is basically an ion channel protein in Streptomyces Lividans and which is taken up to form micelle-protein system and the system is analyzed by using molecular dynamics simulation. Firstly, ion channel pore is engineered by CHARMM potential and then Micelle-protein system is subjected to molecular dynamics simulation. For some specific micelle concentration, the protein unfolding is observed.

Gradient structure-induced temperature responsiveness in styrene/methyl methacrylate gradient copolymers micelles.

PubMed

Zheng, Chao; Huang, Haiying; He, Tianbai

2014-02-01

In this work, micelles are formed by gradient copolymer of styrene and methyl methacrylate in acetone-water mixture and their temperature responsiveness is investigated in a narrow range near room temperature. Three different kinds of structural transitions could be induced by temperature: unimers to micelle transition, shrinkage/stretching of micelles, and morphological transition from spherical micelles to vesicles. In addition, a model analysis on the interface of gradient copolymer micelle is made to better understand these phenomena. It is found that both position and composition of the interface could alter in response to the change in temperature. According to the experiments and model analysis, it is proposed that temperature responsiveness might be an intrinsic and universal property of gradient copolymer micelles, which only originates from the gradient structure. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Self-assembled penetratin-deferasirox micelles as potential carriers for hydrophobic drug delivery.

PubMed

Goswami, Dibakar; Vitorino, Hector Aguilar; Machini, M Teresa; Espósito, Breno P

2015-11-01

There has been a growing interest in the use of micelles with nanofiber geometry as nanocarriers for hydrophobic drugs. Here we show that the conjugate of penetratin, a cell-penetrating peptide (CPP) with blood-brain barrier (BBB) permeability, and deferasirox (DFX), a hydrophobic iron chelator, self-assembles to form micelles at a very low concentration (∼15 mg/L). The critical micelle concentration (CMC) was determined, and the micelles were used for solubilizing curcumin, a hydrophobic anti-neurodegenerative drug, for successful delivery across RBE4 cells, a BBB model. Transmission Electron Microscope images of the curcumin-loaded micelles confirmed the formation of nanofibers. These results indicate the potential of CPP-drug conjugates for use as nanocarriers. © 2015 Wiley Periodicals, Inc.

Interactions in Micellar Solutions of β-Casein

NASA Astrophysics Data System (ADS)

Leclerc, E.; Calmettes, P.

1997-01-01

β-casein is a flexible amphiphilic milk protein which forms spherical micelles in very dilute solution. The magnitude of the weight-average interactions between the solute particles has been inferred from small-angle neutron scattering experiments. At relatively high protein concentrations the interactions between micelles are repulsive, whatever the temperature. At lower concentration these interactions vanish and become more and more attractive when the critical micelle concentration is approached. Although indispensable for micelle formation, this fact seems to have not been previously reported.

Reduction-sensitive micelles self-assembled from amphiphilic chondroitin sulfate A-deoxycholic acid conjugate for triggered release of doxorubicin.

PubMed

Liu, Hongxia; Wu, Shuqin; Yu, Jingmou; Fan, Dun; Ren, Jin; Zhang, Lei; Zhao, Jianguo

2017-06-01

Reduction-sensitive chondroitin sulfate A (CSA)-based micelles were developed. CSA was conjugated with deoxycholic acid (DOCA) via a disulfide linkage. The bioreducible conjugate (CSA-ss-DOCA) can form self-assembled micelles in aqueous medium. The critical micelle concentration (CMC) of CSA-ss-DOCA conjugate is 0.047mg/mL, and its mean diameter is 387nm. The anticancer drug doxorubicin (DOX) was chosen as a model drug, and was effectively encapsulated into the micelles with high loading efficiency. Reduction-sensitive micelles and reduction-insensitive control micelles displayed similar DOX release behavior in phosphate buffered saline (PBS, pH7.4). Notably, DOX release from the reduction-sensitive micelles in vitro was accelerated in the presence of 20mM glutathione-containing PBS environment. Moreover, DOX-loaded CSA-ss-DOCA (CSA-ss-DOCA/DOX) micelles exhibited intracellular reduction-responsive characteristics in human gastric cancer HGC-27 cells determined by confocal laser scanning microscopy (CLSM). Furthermore, CSA-ss-DOCA/DOX micelles demonstrated higher antitumor efficacy than reduction-insensitive control micelles in HGC-27 cells. These results suggested that reduction-sensitive CSA-ss-DOCA micelles had the potential as intracellular targeted carriers of anticancer drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Solution structure of detergent micelles at conditions relevant to membrane protein crystallization.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Littrell, K.; Thiyagarajan, P.; Tiede, D.

1999-07-02

In this study small angle neutron scattering was used to characterize the formation of micelles in aqueous solutions of the detergents DMG and SPC as a function of detergent concentration and ionic strength of the solvent. The effects on the micelle structure of the additives glycerol and PEG, alone as well as in combination typical for actual membrane protein crystallization, were also explored. This research suggests that the micelles are cigar-like in form at the concentrations studied. The size of the micelles was observed to increase with increasing ionic strength but decrease with the addition of glycerol or PEG.

The effect of surface topography on the micellisation of hexadecyltrimethylammonium chloride at the silicon-aqueous interface

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darkins, Robert; Sushko, Maria L.; Liu, Jun

2015-02-11

Amphiphilic aggregation at solid-liquid interfaces can generate mesostructured micelles that can serve as soft templates. In this study we have simulated the self-assembly of hexadecyltrimethylammonium chloride (C16TAC) surfactants at the Si(100)- and Si(111)-aqueous interfaces. The surfactants are found to form semicylindrical micelles on Si(100) but hemispherical micelles on Si(111). This difference in micelle structure is shown to be a consequence of the starkly different surface topographies that result from the reconstruction of the two silicon surfaces. This reveals that micelle structure can be governed by epitaxial matching even with non-polar substrates.

Influence of hydrophobic micelle structure on crystallization of the photosynthetic RC-LH1-PufX complex from Rhodobacter blasticus.

PubMed

Barret, Laurie-Anne; Barrot-Ivolot, Cherone; Raynal, Simon; Jungas, Colette; Polidori, Ange; Bonneté, Françoise

2013-07-25

Small angle X-ray scattering (SAXS) experiments are performed on two non-ionic surfactants, the dodecyl β-maltoside (DDβM) and the propyl(bi)cyclohexyl α-maltoside (PCCαM), a maltoside derivative containing a rigid bicyclohexyl group as hydrophobic chain, in order to compare the influence of both hydrophobic moiety structure and anomeric form on micelle form factors and intermicellar interactions relevant for membrane protein crystallization. Density and refractive index measurements were performed in order to determine volumetric and optical properties of surfactants, essential for determination of micelle molar masses by both SAXS and SEC-MALLS. SAXS form factors were analyzed by Guinier approximation and inverse Fourier transformation, to obtain the radius of gyration (RG) and the pair distribution function (P(r)) of each surfactant. Form factor model fitting was also performed to describe the shape and the assembly of both surfactant micelles. Finally, second virial coefficients were measured at different percentages of polyethylene glycol 3350, in order to correlate surfactant intermicellar interactions and RC-LH1-PufX phase diagram. It is thus found that while size, shape, and dimensions of micelles are slightly similar for both surfactants, their molar mass and aggregation number differ significantly. PCCαM are more densely packed than DDβM, which reflects (1) an increase in van der Waals contacts between PCCαM hydrophobic chains in the micelle bulk and (2) a supplementary intermicellar attraction compared to DDβM. Finally addition of PEG, which induces a depletion attraction, decreases the solubility of the RC-LH1-PufX complex in PCCαM.

Citral degradation in micellar structures formed with polyoxyethylene-type surfactants.

PubMed

Park, Sung Joon; Hong, Chi Rac; Choi, Seung Jun

2015-03-01

In a micellar solution, the chemical degradation of poorly water-soluble food flavours can be influenced by the properties of the surfactants forming the micelles in aqueous solutions. To evaluate how hydrophilic head size and hydrophobic tail length influence the chemical degradation rate of food flavour, micelles were prepared with Brij surfactants (Brij 35, 58, 78 and 700), each of which had very similar molecular structures (polyoxyethylene fatty acid ether). The chemical degradation of citral in Brij micelles was found to be highest in an acidic environment. There was no significant difference in the chemical degradation rate of citral in Brij micelles in non-acidic conditions, regardless of the hydrophilic head size or hydrophobic tail length. Brij surfactants with larger hydrophilic heads effectively retarded the chemical degradation of citral in an acidic environment. Our findings suggest that the length of the hydrophobic tail rarely influenced the micelle's ability to chemically stabilize citral. Copyright © 2014 Elsevier Ltd. All rights reserved.

Amphipathic dextran-doxorubicin prodrug micelles for solid tumor therapy.

PubMed

Jin, Rong; Guo, Xuelian; Dong, Lingli; Xie, Enyuan; Cao, Aoneng

2017-10-01

A group of micelles self-assembled from deoxycholic acid-doxorubicin-conjugated dextran (denoted as Dex-DCA-DOX) prodrugs were designed and prepared for pH-triggered drug release and cancer chemotherapy. These prodrugs could be successfully produced by chemically coupling hydrophobic deoxycholic acid (DCA) to dextran hydrazine (denoted as Dex-NHNH 2 ) and hydrazone linker formation between doxorubicin (DOX) and Dex-NHNH 2 . These Dex-DCA-DOX prodrugs self-assembled to form micelles under physiological conditions with varied particle sizes depending on molecular weight of dextran, degree of substitution (DS) of DCA and DOX. After optimization, Dex10k-DCA9-DOX5.5 conjugate comprising dextran of 10kDa, DCA of DS 9 and DOX loading content of 5.5wt%, formed the micelles with the smallest size (110nm). These prodrug micelles could slowly liberate DOX under physiological conditions but efficiently released the drug at an acidified endosomal pH by the hydrolysis of acid-labile hydrazone linker. In vitro cytotoxicity experiment indicated that Dex10k-DCA9-DOX5.5 micelles exerted marked antitumor activity against MCF-7 and SKOV-3 cancer cells. Besides, intravenous administration of the micelles afforded growth inhibition of SKOV-3 tumor bearing in nude mice at a dosage of 2.5mg per kg with anti-cancer efficacy comparable to free DOX-chemotherapy but low systemic toxicity. This study highlights the feasibility of bio-safe and efficient dextran-based prodrug micelles designed for cancer chemotherapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Self-assembly of star micelle into vesicle in solvents of variable quality: the star micelle retains its core-shell nanostructure in the vesicle.

PubMed

Liu, Nijuan; He, Qun; Bu, Weifeng

2015-03-03

Intra- and intermolecular interactions of star polymers in dilute solutions are of fundamental importance for both theoretical interest and hierarchical self-assembly into functional nanostructures. Here, star micelles with a polystyrene corona and a small ionic core bearing platinum(II) complexes have been regarded as a model of star polymers to mimic their intra- and interstar interactions and self-assembled behaviors in solvents of weakening quality. In the chloroform/methanol mixture solvents, the star micelles can self-assemble to form vesicles, in which the star micelles shrink significantly and are homogeneously distributed on the vesicle surface. Unlike the morphological evolution of conventional amphiphiles from micellar to vesicular, during which the amphiphilic molecules are commonly reorganized, the star micelles still retain their core-shell nanostructures in the vesicles and the coronal chains of the star micelle between the ionic cores are fully interpenetrated.

Engineering single-polymer micelle shape using nonuniform spontaneous surface curvature

NASA Astrophysics Data System (ADS)

Moths, Brian; Witten, T. A.

2018-03-01

Conventional micelles, composed of simple amphiphiles, exhibit only a few standard morphologies, each characterized by its mean surface curvature set by the amphiphiles. Here we demonstrate a rational design scheme to construct micelles of more general shape from polymeric amphiphiles. We replace the many amphiphiles of a conventional micelle by a single flexible, linear, block copolymer chain containing two incompatible species arranged in multiple alternating segments. With suitable segment lengths, the chain exhibits a condensed spherical configuration in solution, similar to conventional micelles. Our design scheme posits that further shapes are attained by altering the segment lengths. As a first study of the power of this scheme, we demonstrate the capacity to produce long-lived micelles of horseshoe form using conventional bead-spring simulations in two dimensions. Modest changes in the segment lengths produce smooth changes in the micelle's shape and stability.

Formation of cage-like particles by poly(amino acid)-based block copolymers in aqueous solution.

PubMed Central

Cudd, A; Bhogal, M; O'Mullane, J; Goddard, P

1991-01-01

When dissolved in N,N-dimethylformamide and then dialyzed against phosphate-buffered saline, A-B-A block copolymers composed of poly [N5-(2-hydroxyethyl)-L-glutamine]-block-poly(gamma-benzyl-L-glutamate)- block-poly [N5-(2-hydroxyethyl)-L-glutamine] form particles. The particles are cage-like structures with average diameters of 300 nm (average polydispersity, 0.3-0.5). They are stable in aqueous solution at 4 degrees C for up to 3 weeks, at which time flocculation becomes apparent. Negative staining and freeze-fracture electron microscopy suggest that cage-like particles are formed by selective association of segregated micelle populations. A model of particle formation is presented in which B blocks form micelles in dimethylformamide. On dialysis against an aqueous solution, the extended A blocks then associate intermolecularly to form rod-shaped micelles, which connect the B block micelles. The result is a meshed cage-like particle. The implications of these observations on the aggregation behavior of polymeric surfactants in dilute solution are discussed. Images PMID:11607245

Micelle Catalysis of an Aromatic Substitution Reaction

ERIC Educational Resources Information Center

Corsaro, Gerald; Smith J. K.

1976-01-01

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)

Encapsulation of nanoclusters in dried gel materials via an inverse micelle/sol gel synthesis

DOEpatents

Martino, Anthony; Yamanaka, Stacey A.; Kawola, Jeffrey S.; Showalter, Steven K.; Loy, Douglas A.

1998-01-01

A dried gel material sterically entrapping nanoclusters of a catalytically active material and a process to make the material via an inverse micelle/sol-gel synthesis. A surfactant is mixed with an apolar solvent to form an inverse micelle solution. A salt of a catalytically active material, such as gold chloride, is added along with a silica gel precursor to the solution to form a mixture. To the mixture are then added a reducing agent for the purpose of reducing the gold in the gold chloride to atomic gold to form the nanoclusters and a condensing agent to form the gel which sterically entraps the nanoclusters. The nanoclusters are normally in the average size range of from 5-10 nm in diameter with a monodisperse size distribution.

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

PubMed

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

2013-09-05

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.

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

NASA Astrophysics Data System (ADS)

Shi, Yanan; Sun, Fengying; Wang, Dan; Zhang, Renyu; Dou, Changlin; Liu, Wanhui; Sun, Kaoxiang; Li, Youxin

2013-10-01

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.

A hypothetical hierarchical mechanism of the self-assembly of the Escherichia coli RNA polymerase σ(70) subunit.

PubMed

Koroleva, O N; Dubrovin, E V; Tolstova, A P; Kuzmina, N V; Laptinskaya, T V; Yaminsky, I V; Drutsa, V L

2016-02-21

Diverse morphology of aggregates of amyloidogenic proteins has been attracting much attention in the last few years, and there is still no complete understanding of the relationships between various types of aggregates. In this work, we propose the model, which universally explains the formation of morphologically different (wormlike and rodlike) aggregates on the example of a σ(70) subunit of RNA polymerase, which has been recently shown to form amyloid fibrils. Aggregates were studied using AFM in solution and depolarized dynamic light scattering. The obtained results demonstrate comparably low Young's moduli of the wormlike structures (7.8-12.3 MPa) indicating less structured aggregation of monomeric proteins than that typical for β-sheet formation. To shed light on the molecular interaction of the protein during the aggregation, early stages of fibrillization of the σ(70) subunit were modeled using all-atom molecular dynamics. Simulations have shown that the σ(70) subunit is able to form quasi-symmetric extended dimers, which may further interact with each other and grow linearly. The proposed general model explains different pathways of σ(70) subunit aggregation and may be valid for other amyloid proteins.

KE108-conjugated unimolecular micelles loaded with a novel HDAC inhibitor thailandepsin-A for targeted neuroendocrine cancer therapy.

PubMed

Chen, Guojun; Jaskula-Sztul, Renata; Harrison, April; Dammalapati, Ajitha; Xu, Wenjin; Cheng, Yiqiang; Chen, Herbert; Gong, Shaoqin

2016-08-01

Neuroendocrine (NE) cancers can cause significant patient morbidity. Besides surgery, there are no curative treatments for NE cancers and their metastases, emphasizing the need for the development of other forms of therapy. In this study, multifunctional unimolecular micelles were developed for targeted NE cancer therapy. The unimolecular micelles were formed by multi-arm star amphiphilic block copolymer poly(amidoamine)-poly(valerolactone)-poly(ethylene glycol) conjugated with KE108 peptide and Cy5 dye (abbreviated as PAMAM-PVL-PEG-KE108/Cy5). The unimolecular micelles with a spherical core-shell structure exhibited a uniform size distribution and excellent stability. The hydrophobic drug thailandepsin-A (TDP-A), a recently discovered HDAC inhibitor, was physically encapsulated into the hydrophobic core of the micelles. KE108 peptide, a somatostatin analog possessing high affinity for all five subtypes of somatostatin receptors (SSTR 1-5), commonly overexpressed in NE cancer cells, was used for the first time as an NE cancer targeting ligand. KE108 exhibited superior targeting abilities compared to other common somatostatin analogs, such as octreotide, in NE cancer cell lines. The in vitro assays demonstrated that the TDP-A-loaded, KE108-targeted micelles exhibited the best capabilities in suppressing NE cancer cell growth. Moreover, the in vivo near-infrared fluorescence imaging on NE-tumor-bearing nude mice showed that KE108-conjugated micelles exhibited the greatest tumor accumulation due to their passive targeting and active targeting capabilities. Finally, TDP-A-loaded and KE108-conjugated micelles possessed the best anticancer efficacy without detectable systemic toxicity. Thus, these novel TDP-A-loaded and KE108-conjugated unimolecular micelles offer a promising approach for targeted NE cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Encapsulation Efficiency and Micellar Structure of Solute-Carrying Block Copolymer Nanoparticles

PubMed Central

Woodhead, Jeffrey L.; Hall, Carol K.

2011-01-01

We use discontinuous molecular dynamics (DMD) computer simulation to investigate the encapsulation efficiency and micellar structure of solute-carrying block copolymer nanoparticles as a function of packing fraction, polymer volume fraction, solute mole fraction, and the interaction parameters between the hydrophobic head blocks and between the head and the solute. The encapsulation efficiency increases with increasing polymer volume fraction and packing fraction but decreases with increasing head-head interaction strength. The latter is due to an increased tendency for the solute to remain on the micelle surface. We compared two different nanoparticle assembly methods, one in which the solute and copolymer co-associate and the other in which the copolymer micelle is formed before the introduction of solute. The assembly method does not affect the encapsulation efficiency but does affect the solute uptake kinetics. Both head-solute interaction strength and head-head interaction strength affect the density profile of the micelles; increases in the former cause the solute to distribute more evenly throughout the micelle, while increases in the latter cause the solute to concentrate further from the center of the micelle. We explain our results in the context of a model of drug insertion into micelles formulated by Kumar and Prud’homme; as conditions become more conducive to micelle formation, a stronger energy barrier to solute insertion forms which in turn decreases the encapsulation efficiency of the system. PMID:21918582

Micelles As Delivery System for Cancer Treatment.

PubMed

Keskin, Dilek; Tezcaner, Aysen

2017-01-01

Micelles are nanoparticles formed by the self-assembly of amphiphilic block copolymers in certain solvents above concentrations called critical micelle concentration (CMC). Micelles are used in different fields like food, cosmetics, medicine, etc. These nanosized delivery systems are under spotlight in the recent years with new achievements in terms of their in vivo stability, ability to protect entrapped drug, release kinetics, ease of cellular penetration and thereby increased therapeutic efficacy. Drug loaded micelles can be prepared by dialysis, oil-in-water method, solid dispersion, freezing, spray drying, etc. The aim of this review is to give an overview of the research on micelles (in vitro, in vivo and clinical) as delivery system for cancer treatment. Passive targeting is one route for accumulation of nanosized micellar drug formulations. Many research groups from both academia and industry focus on developing new strategies for improving the therapeutic efficacy of micellar systems (active targeting to the tumor site, designing multidrug delivery systems for overcoming multidrug resistance or micelles formed by prodrug conjugates, etc). There is only one micellar drug formulation in South Korea that has reached clinical practice. However, there are many untargeted anticancer drug loaded micellar formulations in clinical trials, which have potential for use in clinics. Many more products are expected to be on the market in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Micellar Sink

PubMed Central

Scharschmidt, Bruce F.; Schmid, Rudi

1978-01-01

Although the importance of mixed micelles in the solubilization and biliary excretion of lipids is established, little is known about a possible role of mixed micelles in the excretion of other biliary solutes. Ultrafiltration and ultracentrifugation techniques were used to investigate the interaction between substances that are excreted in bile and biliary mixed micelles. Substances (urea, erythritol, sucrose) excreted in bile at concentrations equal to, or less than, that in plasma did not show an association with mixed micelles, whereas substances (indocyanine green, iopanoic acid, rose bengal, unconjugated and conjugated sulfobromophthalein, and conjugated bilirubin) excreted in bile at high concentration relative to plasma did. The percentage of these latter substances in bile associated with micelles varied from 26 to 93% and was relatively independent of concentration. In addition to their association with mixed micelles, these test solutes formed self-aggregates that were stabilized primarily by ionic bonds, and only a small percentage (range = 0-5%) of these solutes were present in bile in the form of monomer or complexes small enough to pass a 5,000-mol wt membrane. These findings offer a possible explanation for the increase in sulfobromophthalein, bilirubin, and indocyanine green maximal biliary excretory rate produced by bile salt infusion, and suggest that the concentrative transport into bile of endogenous compounds and xenobiotics may result from their incorporation into mixed micelles and other macromolecular complexes. PMID:748371

A 1H-n.m.r. study of casein micelles.

PubMed Central

Griffin, M C; Roberts, G C

1985-01-01

The 1H-n.m.r. spectrum of casein micelles consists of a small number of moderately sharp (linewidth approx. 60 Hz) resonances superimposed on the envelope of very broad lines expected for particles of this size. These sharp lines resemble, in chemical shift and relative intensity, the spectrum of the isolated 'macropeptide' released from the micelles by treatment with chymosin. The sharp lines in the casein micelle spectrum are further sharpened by addition of chymosin and broadened markedly by addition of ethanol. These observations are consistent with the proposal that the 'macropeptide' (the C-terminal 64 residues of K-casein) forms flexible 'hairs' on the surface of the micelles. PMID:3924034

Delta-opiate DPDPE in magnetically oriented phospholipid micelles: binding and arrangement of aromatic pharmacophores.

PubMed Central

Rinaldi, F; Lin, M; Shapiro, M J; Petersheim, M

1997-01-01

D-Penicillamine(2,5)-enkephalin (DPDPE) is a potent opioid peptide that exhibits a high selectivity for the delta-opiate receptors. This zwitterionic peptide has been shown, by pulsed-field gradient 1H NMR diffusion studies, to have significant affinity for a zwitterionic phospholipid bilayer. The bilayer lipid is in the form of micelles composed of dihexanoylphosphatidylcholine (DHPC) and dimyristoylphosphatidylcholine (DMPC) mixtures, where the DMPC forms the bilayer structure. At high lipid concentration (25% w/w) these micelles orient in the magnetic field of an NMR spectrometer. The resulting 1H-13C dipolar couplings and chemical shift changes in the natural abundance 13C resonances for the Tyr and Phe aromatic rings were used to characterize the orientations in the bilayer micelles of these two key pharmacophores. Images FIGURE 1 FIGURE 8 PMID:9414244

High fluorescent water soluble CdTe quantum dots—a promising system for light harvesting applications

NASA Astrophysics Data System (ADS)

de Sa, Arsenio; Moura, Isabel; Abreu, Ana S.; Oliveira, Manuel; Ferreira, Miguel F.; Machado, Ana V.

2017-05-01

The entrapment of quantum dots (QDs) in the inner part of micelles formed by surfactant polymers is a powerful methodology to prepare stable and photoluminescent core nanoparticles with enhanced optical properties. These features are crucial for the application of QDs in the design of hybrid assemblies for light harvesting applications, where energy transfer processes are required. The present work was focused on the synthesis of a surfactant homopolymer, poly (acrylic acid) (PAA) macroRAFT, to be used as a stabilizer of hydrophobic cadmium telluride (CdTe) QDs in aqueous solution. PAA macroRAFT was synthesized by reversible addition-fragmentation chain-transfer (RAFT) polymerization in a single chemical reaction. Its micelles were used to entangle and entrap hydrophobic CdTe QDs, with different molar ratio of polymer and QDs. The morphology and optical properties of the entrapped QDs were determined. The results showed that PAA macroRAFT is able to form micelles with a critical micelle concentration of 2.08 mg/mL. It was also noticed that the molar ratio of polymer and QDs have high influence on the QDs' morphology and their optical properties. The QDs' photoluminescence quantum yield was enhanced approximately 23% upon their entrapment in PAA macroRAFT micelles, using 60 equivalents of polymer. Moreover, while in solution, QDs are well-dispersed, having a 3.5 nm diameter, upon being entrapped in the micelles, tend to form clusters with a size around 100 nm.

Encapsulation of nanoclusters in dried gel materials via an inverse micelle/sol gel synthesis

DOEpatents

Martino, A.; Yamanaka, S.A.; Kawola, J.S.; Showalter, S.K.; Loy, D.A.

1998-09-29

A dried gel material sterically entrapping nanoclusters of a catalytically active material and a process to make the material via an inverse micelle/sol-gel synthesis are disclosed. A surfactant is mixed with an apolar solvent to form an inverse micelle solution. A salt of a catalytically active material, such as gold chloride, is added along with a silica gel precursor to the solution to form a mixture. To the mixture are then added a reducing agent for the purpose of reducing the gold in the gold chloride to atomic gold to form the nanoclusters and a condensing agent to form the gel which sterically entraps the nanoclusters. The nanoclusters are normally in the average size range of from 5--10 nm in diameter with a monodisperse size distribution. 1 fig.

Uniform two-dimensional square assemblies from conjugated block copolymers driven by π–π interactions with controllable sizes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Liang; Wang, Meijing; Jia, Xiangmeng

Two-dimensional (2-D) micro- and nano- architectures are attractive because of their unique properties caused by their ultrathin and flat morphologies. However, the formation of 2-D supramolecular highly symmetrical structures with considerable control is still a major challenge. Here, we presented a simple approach for the preparation of regular and homogeneous 2-D fluorescent square noncrystallization micelles with conjugated diblock copolymers PPV12-b-P2VPn through a process of dissolving-cooling-aging. The scale of the formed micelles could be controlled by the ratio of PPV/P2VP blocks and the concentration of the solution. The forming process of the platelet square micelles was analyzed by UV-Vis, DLS andmore » SLS, while the molecular arrangement was characterized by GIXD. The results revealed that the micelles of PPV12-b-P2VPn initially form 1-D structures and then grow into 2-D structures in solution, and the growth is driven by intermolecular π-π interactions with the PPV12 blocks. The formation of 2-D square micelles is induced by herringbone arrangement of the molecules, which is closely related to the presence of the branched alkyl chains attached to conjugated PPV12 cores.« less

Magnetic Heating of Iron Oxide Nanoparticles and Magnetic Micelles for Cancer Therapy.

PubMed

Glover, Amanda L; Bennett, James B; Pritchett, Jeremy S; Nikles, Sarah M; Nikles, David E; Nikles, Jacqueline A; Brazel, Christopher S

2013-01-01

The inclusion of magnetic nanoparticles into block copolymer micelles was studied towards the development of a targeted, magnetically triggered drug delivery system for cancer therapy. Herein, we report the synthesis of magnetic nanoparticles and poly(ethylene glycol-b-caprolactone) block copolymers, and experimental verification of magnetic heating of the nanoparticles, self-assembly of the block copolymers to form magnetic micelles, and thermally-enhanced drug release. The semicrystalline core of the micelles melted at temperatures just above physiological conditions, indicating that they could be used to release a chemotherapy agent from a thermo-responsive polymer system. The magnetic nanoparticles were shown to heat effectively in high frequency magnetic fields ranging from 30-70 kA/m. Magnetic micelles also showed heating properties, that when combined with a chemotherapeutic agent and a targeting ligand could be developed for localized, triggered drug delivery. During the magnetic heating experiments, a time lag was observed in the temperature profile for magnetic micelles, likely due to the heat of fusion of melting of polycaprolactone micelle cores before bulk solution temperatures increased. Doxorubicin, incorporated into the micelles, released faster when the micelles were heated above the core melting point.

Block copolymer micelles for controlled delivery of glycolytic enzyme inhibitors.

PubMed

Akter, Shanjida; Clem, Brian F; Lee, Hyun Jin; Chesney, Jason; Bae, Younsoo

2012-03-01

To develop block copolymer micelles as an aqueous dosage form for a potent glycolytic enzyme inhibitor, 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO). The micelles were prepared from poly(ethylene glycol)-poly(aspartate hydrazide) [PEG-p(HYD)] block copolymers to which 3PO was conjugated through an acid-labile hydrazone bond. The optimal micelle formulation was determined following the screening of block copolymer library modified with various aromatic and aliphatic pendant groups. Both physical drug entrapment and chemical drug conjugation methods were tested to maximize 3PO loading in the micelles during the screening. Particulate characterization showed that the PEG-p(HYD) block copolymers conjugated with 3PO (2.08∼2.21 wt.%) appeared the optimal polymer micelles. Block copolymer compositions greatly affected the micelle size, which was 38 nm and 259 nm when 5 kDa and 12 kDa PEG chains were used, respectively. 3PO release from the micelles was accelerated at pH 5.0, potentiating effective drug release in acidic tumor environments. The micelles retained biological activity of 3PO, inhibiting various cancer cells (Jurkat, He-La and LLC) in concentration ranges similar to free 3PO. A novel micelle formulation for controlled delivery of 3PO was successfully prepared.

Drug-conjugated PLA-PEG-PLA copolymers: a novel approach for controlled delivery of hydrophilic drugs by micelle formation.

PubMed

Danafar, H; Rostamizadeh, K; Davaran, S; Hamidi, M

2017-12-01

A conjugate of the antihypertensive drug, lisinopril, with triblock poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) copolymer was synthesized by the reaction of PLA-PEG-PLA copolymer with lisinopril in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The conjugated copolymer was characterized in vitro by hydrogen nuclear magnetic resonance (HNMR), Fourier transform infrared (FTIR), differential scanning calorimetry (DSC) and gel permeation chromatography (GPC) techniques. Then, the lisinopril conjugated PLA-PEG-PLA were self-assembled into micelles in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM). The results revealed that the micelles formed by the lisinopril-conjugated PLA-PEG-PLA have spherical structure with the average size of 162 nm. The release behavior of conjugated copolymer, micelles and micelles physically loaded by lisinopril were compared in different media. In vitro release study showed that in contrast to physically loaded micelles, the release rate of micelles consisted of the conjugated copolymer was dependent on pH of media where it was higher at lower pH compared to the neutral medium. Another feature of the conjugated micelles was their more sustained release profile compared to the lisinopril-conjugated copolymer and physically loaded micelles.

Analog modeling of Worm-Like Chain molecules using macroscopic beads-on-a-string.

PubMed

Tricard, Simon; Feinstein, Efraim; Shepherd, Robert F; Reches, Meital; Snyder, Phillip W; Bandarage, Dileni C; Prentiss, Mara; Whitesides, George M

2012-07-07

This paper describes an empirical model of polymer dynamics, based on the agitation of millimeter-sized polymeric beads. Although the interactions between the particles in the macroscopic model and those between the monomers of molecular-scale polymers are fundamentally different, both systems follow the Worm-Like Chain theory.

Cellular localization and detergent dependent oligomerization of rice allene oxide synthase-1.

PubMed

Yoeun, Sereyvath; Kim, Jeong-Il; Han, Oksoo

2015-01-01

Allene oxide synthase-1 from Oryza sativa (OsAOS1) localizes to the chloroplast, but lacks a putative chloroplast targeting sequence typically found in dicot AOS. Here, kinetic parameters and the oligomerization state/subunit composition of OsAOS1 were characterized in vitro in the absence or presence of detergent micelles. The catalytic efficiency (k(cat)/K(m)) of OsAOS1 reached a maximum near the critical micelle concentration for polyoxyethylene 10 tridecyl ether. Native gel analysis showed that OsAOS1 exists as a multimer in the absence of detergent micelles. The multimeric form of OsAOS1 was stably cross-linked in the absence of detergents, while only monomeric OsAOS1 was detected in the presence of detergent micelles. Gel filtration analysis indicated that the oligomeric state of OsAOS1 depends strongly on the detergents and that the monomer becomes the predominant form in the presence of detergent micelles. These data suggest that the detergent-dependent oligomeric state of OsAOS1 is an important factor for the regulation of its catalytic efficiency.

Interactions between tea catechins and casein micelles and their impact on renneting functionality.

PubMed

Haratifar, Sanaz; Corredig, Milena

2014-01-15

Many studies have shown that tea catechins bind to milk proteins. This research focused on the association of tea polyphenols with casein micelles, and the consequences of the interactions on the renneting behaviour of skim milk. It was hypothesized that epigallocatechin-gallate (EGCG), the main catechin present in green tea, forms complexes with the casein micelles and that the association modifies the processing functionality of casein micelles. The binding of EGCG to casein micelles was quantified using HPLC. The formation of catechin-casein micelles complexes affected the rennet induced gelation of milk, and the effect was concentration dependent. Both the primary as well as the secondary stage of gelation were affected. These experiments clearly identify the need for a better understanding of the effect of tea polyphenols on the processing functionality of casein micelles, before milk products can be used as an appropriate platform for delivery of bioactive compounds. Copyright © 2013 Elsevier Ltd. All rights reserved.

Microfibres and macroscopic films from the coordination-driven hierarchical self-assembly of cylindrical micelles

PubMed Central

Lunn, David J.; Gould, Oliver E. C.; Whittell, George R.; Armstrong, Daniel P.; Mineart, Kenneth P.; Winnik, Mitchell A.; Spontak, Richard J.; Pringle, Paul G.; Manners, Ian

2016-01-01

Anisotropic nanoparticles prepared from block copolymers are of growing importance as building blocks for the creation of synthetic hierarchical materials. However, the assembly of these structural units is generally limited to the use of amphiphilic interactions. Here we report a simple, reversible coordination-driven hierarchical self-assembly strategy for the preparation of micron-scale fibres and macroscopic films based on monodisperse cylindrical block copolymer micelles. Coordination of Pd(0) metal centres to phosphine ligands immobilized within the soluble coronas of block copolymer micelles is found to induce intermicelle crosslinking, affording stable linear fibres comprised of micelle subunits in a staggered arrangement. The mean length of the fibres can be varied by altering the micelle concentration, reaction stoichiometry or aspect ratio of the micelle building blocks. Furthermore, the fibres aggregate on drying to form robust, self-supporting macroscopic micelle-based thin films with useful mechanical properties that are analogous to crosslinked polymer networks, but on a longer length scale. PMID:27538877

Photocytotoxicity of mTHPC (Temoporfin) Loaded Polymeric Micelles Mediated by Lipase Catalyzed Degradation

PubMed Central

Hofman, Jan-Willem; Carstens, Myrra G.; van Zeeland, Femke; Helwig, Conny; Flesch, Frits M.; Hennink, Wim E.

2008-01-01

Purpose To study the in vitro photocytotoxicity and cellular uptake of biodegradable polymeric micelles loaded with the photosensitizer mTHPC, including the effect of lipase-catalyzed micelle degradation. Methods Micelles of mPEG750-b-oligo(ɛ-caprolactone)5 (mPEG750-b-OCL5) with a hydroxyl (OH), benzoyl (Bz) or naphthoyl (Np) end group were formed and loaded with mTHPC by the film hydration method. The cellular uptake of the loaded micelles, and their photocytotoxicity on human neck squamous carcinoma cells in the absence and presence of lipase were compared with free and liposomal mTHPC (Fospeg®). Results Micelles composed of mPEG750-b-OCL5 with benzoyl and naphtoyl end groups had the highest loading capacity up to 30% (w/w), likely due to π–π interactions between the aromatic end group and the photosensitizer. MTHPC-loaded benzoylated micelles (0.5 mg/mL polymer) did not display photocytotoxicity or any mTHPC-uptake by the cells, in contrast to free and liposomal mTHPC. After dilution of the micelles below the critical aggregation concentration (CAC), or after micelle degradation by lipase, photocytotoxicity and cellular uptake of mTHPC were restored. Conclusion The high loading capacity of the micelles, the high stability of mTHPC-loaded micelles above the CAC, and the lipase-induced release of the photosensitizer makes these micelles very promising carriers for photodynamic therapy in vivo. PMID:18597164

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Hailong; Li, Ji; Shi, Ke

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. Themore » 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.« less

Solubilization of poorly soluble photosensitizer hypericin by polymeric micelles and polyethylene glycol.

PubMed

Búzová, Diana; Kasák, Peter; Miškovský, Pavol; Jancura, Daniel

2013-06-01

Hypericin (Hyp) is a promising photosensitizer for photodiagnostic and photodynamic therapy of cancer. However, Hyp has a large conjugated system and in aqueous solutions forms insoluble aggregates which do not possess biological activity. This makes intravenous injection of Hyp problematic and restricts its medical applications. To overcome this problem, Hyp is incorporated into drug delivery systems which can increase its solubility and bioavailability. One of the possibilities is utilization of polymeric micelles. The most used hydrophilic block for preparation of polymeric micelles is polyethylen glycol (PEG). PEG is a polymer which for its lack of immunogenicity, antigenicity and toxicity obtained approval for use in human medicine. In this work we have studied the solubilization of Hyp aggregates in the presence of PEG-PE and PEG-cholesterol micelles. The concentration of polymeric micelles which allows total monomerization of Hyp corresponds to the critical micellar concentration of these micelles (~10(-6) M). We have also investigated the effect of the molecular weight and concentration of PEG on the transition of aggregated Hyp to its monomeric form. PEGs with low molecular weight (< 1000 g/mol) do not significantly contribute to the solubilization of Hyp. However, PEGs with molecular weight > 2000 g/mol efficiently transform Hyp aggregates to the monomeric state of this photosensitizer.

Spontaneous Evolution of Nanostructure in Composite Films Consisting of Mixtures of Two Different Block Copolymer Micelles

NASA Astrophysics Data System (ADS)

Kim, Sehee; Char, Kookheon; Sohn, Byeong-Hyeok

2010-03-01

Diblock copolymers consisting of two immiscible polymer blocks covalently bonded together form various self-assembled nanostructures such as spheres, cylinders, and lamellae in bulk phase. In a selective solvent, however, they assemble into micelles with soluble corona brushes and immiscible cores. Both polystyrene-poly(4-vinylpyridine) (PS-b-P4VP) and polystyrene-poly(2-vinylpyridine) (PS-b-P2VP) diblock copolymers form micelles with PS coronas and P4VP or P2VP cores in a PS selective solvent (toluene). By varying the mixture ratio between PS-b-P4VP and PS-b-P2VP, composite films based on the micellar mixtures of PS-b-P4VP and PS-b-P2VP were obtained by spin-coating, followed by the solvent annealing with tetrahydrofuran (THF) vapor. Since THF is a solvent for both PS and P2VP blocks and, at the same time, a non-solvent for the P4VP block, PS-P2VP micelles transformed to lamellar multilayers while PS-P4VP micelles remained intact during the THF annealing. The spontaneous evolution of nanostructure in composite films consisting of lamellae layers with BCP micelles were investigated in detail by cross-sectional TEM and AFM.

Processes for microemulsion polymerization employing novel microemulsion systems

DOEpatents

Beckman, Eric J.; Smith, Richard D.; Fulton, John L.

1990-06-12

This invention is directed to a microemulsion system comprising a first phase including a low-polarity fluid material which is a gas at standard temperature and pressure, and which has a cloud-point density. It also includes a second phase including a polar fluid, typically water, a monomer, preferably a monomer soluble in the polar fluid, and a microemulsion promoter for facilitating the formation of micelles including the monomer in the system. In the subject process, micelles including the monomer are formed in the first phase. A polymerization initiator is introduced into the micelles in the microemulsion system. The monomer is then polymerized in the micelles, preferably in the core of the micelle, to produce a polymeric material having a relatively high molecular weight.

Polymeric micelles: nanocarriers for cancer-targeted drug delivery.

PubMed

Zhang, Yifei; Huang, Yixian; Li, Song

2014-08-01

Polymeric micelles represent an effective delivery system for poorly water-soluble anticancer drugs. With small size (10-100 nm) and hydrophilic shell of PEG, polymeric micelles exhibit prolonged circulation time in the blood and enhanced tumor accumulation. In this review, the importance of rational design was highlighted by summarizing the recent progress on the development of micellar formulations. Emphasis is placed on the new strategies to enhance the drug/carrier interaction for improved drug-loading capacity. In addition, the micelle-forming drug-polymer conjugates are also discussed which have both drug-loading function and antitumor activity.

Antimicrobial activity of topically-applied soyaethyl morpholinium ethosulfate micelles against Staphylococcus species.

PubMed

Yang, Shih-Chun; Aljuffali, Ibrahim A; Sung, Calvin T; Lin, Chwan-Fwu; Fang, Jia-You

2016-03-01

Here we evaluated the antibacterial efficacy of soyaethyl morpholinium ethosulfate (SME) micelles as an inherent bactericide against Staphylococcus aureus and methicillin-resistant S. aureus (MRSA). The antimicrobial activity was examined by in vitro culture model and murine model of skin infection. Cationic micelles formed by benzalkonium chloride or cetylpyridinium chloride were used for comparison. The minimum inhibitory concentration and minimum bactericidal concentration against S. aureus and MRSA were 1.71-3.42 and 1.71-6.84 μg/ml, respectively. Topical administration of SME micelles significantly decreased the cutaneous infection and MRSA load in mice. The killing of bacteria was caused by direct cell wall/membrane rupture. SME micelles also penetrated into the bacteria to elicit a Fenton reaction and oxidative stress. SME micelles have potential as antimicrobial agents due to their lethal effect against S. aureus and MRSA with a low toxicity to mammalian cells.

Competing processes of micellization and fibrillization in native and reduced casein proteins.

PubMed

Portnaya, Irina; Avni, Sharon; Kesselman, Ellina; Boyarski, Yoav; Sukenik, Shahar; Harries, Daniel; Dan, Nily; Cogan, Uri; Danino, Dganit

2016-08-10

Kappa-casein (κCN) and beta-casein (βCN) are disordered proteins present in mammalian milk. In vitro, βCN self-assembles into core-shell micelles. κCN self assembles into similar micelles, as well as into amyloid-like fibrils. Recent studies indicate that fibrillization can be suppressed by mixing βCN and κCN, but the mechanism of fibril inhibition has not been identified. Examining the interactions of native and reduced kappa-caseins (N-κCN and R-κCN) with βCN, we expose a competition between two different self-assembly processes: micellization and fibrillization. Quite surprisingly, however, we find significant qualitative and quantitative differences in the self-assembly between the native and reduced κCN forms. Specifically, thermodynamic analysis reveals exothermic demicellization for βCN and its mixtures with R-κCN, as opposed to endothermic demicellization of N-κCN and its mixtures with βCN at the same temperature. Furthermore, with time, R-κCN/βCN mixtures undergo phase separation into pure βCN micelles and R-κCN fibrils, while in the N-κCN/βCN mixtures fibril formation is considerably delayed and mixed micelles persist for longer periods of time. Fibrils formed in N-κCN/βCN mixtures are shorter and more flexible than those formed in R-κCN/βCN systems. Interestingly, in the N-κCN/βCN mixtures, the sugar moieties of N-κCN oligomers seem to organize on the mixed micelles surface in a manner similar to the organization of κCN in milk casein micelles.

Spectroscopic investigation of the pH controlled inclusion of doxycycline and oxytetracycline antibiotics in cationic micelles and their magnesium driven release.

PubMed

Cesaretti, Alessio; Carlotti, Benedetta; Gentili, Pier Luigi; Clementi, Catia; Germani, Raimondo; Elisei, Fausto

2014-07-24

This work presents a steady-state and time-resolved UV-visible spectroscopic investigation of two antibiotics belonging to the family of tetracyclines (doxycycline and oxytetracycline) in the micellar medium provided by p-dodecyloxybenzyltrimethylammonium bromide (pDoTABr). The spectroscopic analysis has been performed in absorption and emission with femtosecond time resolution, and at pH 5.0 and 8.7 where doxycycline and oxytetracycline are present in their neutral-zwitterionic and monoanionic forms, respectively. The experimental data have been processed by sophisticated data mining methods such as global/target analysis and the maximum entropy method. The results unambiguously indicate that, when doxycycline and oxytetracycline are in their zwitterionic form, they are entrapped within the micelle, while when they are in their monoanionic form, they preferentially show a strong one-to-one interaction with the positively charged surfactant heads. Thus, the pH of the solution controls the inclusion of the investigated drugs into the micelle. When the drugs are entrapped inside the micelles, their spectroscopic and dynamical properties after photoexcitation change appreciably. Interestingly, the entrapped drugs are still able to strongly bind Mg(2+) cations, crucial in determining the biological functioning of tetracyclines. The femtosecond resolved measurements reveal that the drugs are efficiently pulled out of the micelles by Mg(2+). In fact, magnesium-tetracycline complexes are detected in the aqueous phase. The present study suggests the potential promising use of ammonium surfactant micelles embedding doxycycline and oxytetracycline as "smart" drug delivery systems allowing their pH controlled inclusion and Mg(2+) induced release.

Development of casein microgels from cross-linking of casein micelles by genipin.

PubMed

Silva, Naaman F Nogueira; Saint-Jalmes, Arnaud; de Carvalho, Antônio F; Gaucheron, Frédéric

2014-09-02

Casein micelles are porous colloidal particles, constituted of casein molecules, water, and minerals. The vulnerability of the supramolecular structure of casein micelles face to changes in the environmental conditions restrains their applications in other domains besides food. Thus, redesigning casein micelles is a challenge to create new functionalities for these biosourced particles. The objective of this work was to create stable casein microgels from casein micelles using a natural cross-linker, named genipin. Suspensions of purified casein micelles (25 g L(-1)) were mixed with genipin solutions to have final concentrations of 5, 10, and 20 mM genipin. Covalently linked casein microgels were formed via cross-linking of lysyl and arginyl residues of casein molecules. The reacted products exhibited blue color. The cross-linking reaction induced gradual changes on the colloidal properties of the particles. The casein microgels were smaller and more negatively charged and presented smoother surfaces than casein micelles. These results were explained based on the cross-linking of free NH2 present in an external layer of κ-casein. Light scattering and rheological measurements showed that the reaction between genipin and casein molecules was intramicellar, as one single population of particles was observed and the values of viscosity (and, consequently, the volume fraction of the particles) were reduced. Contrary to the casein micelles, the casein microgels were resistant to the presence of dissociating agents, e.g., citrate (calcium chelating) and urea, but swelled as a consequence of internal electrostatic repulsion and the disruption of hydrophobic interactions between protein chains. The casein microgels did not dissociate at the air-solution interface and formed solid-like interfaces rather than a viscoelastic gel. The potential use of casein microgels as adaptable nanocarriers is proposed in the article.

Non-surface activity and micellization behavior of cationic amphiphilic block copolymer synthesized by reversible addition-fragmentation chain transfer process.

PubMed

Ghosh, Arjun; Yusa, Shin-ichi; Matsuoka, Hideki; Saruwatari, Yoshiyuki

2011-08-02

Cationic amphiphilic diblock copolymers of poly(n-butylacrylate)-b-poly(3-(methacryloylamino)propyl)trimethylammonium chloride) (PBA-b-PMAPTAC) with various hydrophobic and hydrophilic chain lengths were synthesized by a reversible addition-fragmentation chain transfer (RAFT) process. Their molecular characteristics such as surface activity/nonactivity were investigated by surface tension measurements and foam formation observation. Their micelle formation behavior and micelle structure were investigated by fluorescence probe technique, static and dynamic light scattering (SLS and DLS), etc., as a function of hydrophilic and hydrophobic chain lengths. The block copolymers were found to be non-surface active because the surface tension of the aqueous solutions did not change with increasing polymer concentration. Critical micelle concentration (cmc) of the polymers could be determined by fluorescence and SLS measurements, which means that these polymers form micelles in bulk solution, although they were non-surface active. Above the cmc, the large blue shift of the emission maximum of N-phenyl-1-naphthylamine (NPN) probe and the low micropolarity value of the pyrene probe in polymer solution indicate the core of the micelle is nonpolar in nature. Also, the high value of the relative intensity of the NPN probe and the fluorescence anisotropy of the 1,6-diphenyl-1,3,5-hexatriene (DPH) probe indicated that the core of the micelle is highly viscous in nature. DLS was used to measure the average hydrodynamic radii and size distribution of the copolymer micelles. The copolymer with the longest PBA block had the poorest water solubility and consequently formed micelles with larger size while having a lower cmc. The "non-surface activity" was confirmed for cationic amphiphilic diblock copolymers in addition to anionic ones studied previously, indicating the universality of non-surface activity nature.

Facile fabrication of core cross-linked micelles by RAFT polymerization and enzyme-mediated reaction.

PubMed

Wu, Yukun; Lai, Quanyong; Lai, Shuqi; Wu, Jing; Wang, Wei; Yuan, Zhi

2014-06-01

Polymeric micelles formed in aqueous solution by assembly of amphiphilic block copolymers have been extensively investigated due to their great potential as drug carriers. However, the stability of polymeric assembly is still one of the major challenges in delivering drugs to tissues and cells. Here, we report a facile route to fabricate core cross-linked (CCL) micelles using an enzymatic polymerization as the cross-linking method. We present synthesis of poly(ethylene glycol)-block-poly(N-isopropyl acrylamide-co-N-(4-hydroxyphenethyl) acrylamide) diblock copolymer PEG-b-P(NIPAAm-co-NHPAAm) via reversible addition-fragmentation chain transfer (RAFT) polymerization. The diblock copolymer was then self-assembled into non-cross-linked (NCL) micelles upon heating above the lower critical solution temperature (LCST), and subsequently cross-linked using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) as enzyme and oxidant. The characterization of the diblock copolymer and micelles were studied by NMR, DLS, UV-vis, and fluorescence spectroscopy. The fluorescence study reveals that the cross-linking process endows the micelles with much lower critical micelle concentration (CMC). In addition, the drug release study shows that the CCL micelles have lower release amount of doxorubicin (DOX) than the NCL micelles due to the enhanced stability of the CCL micelles by core cross-linking process. Copyright © 2014 Elsevier B.V. All rights reserved.

Solubilization of docetaxel in poly(ethylene oxide)-block-poly(butylene/styrene oxide) micelles.

PubMed

Elsabahy, Mahmoud; Perron, Marie-Eve; Bertrand, Nicolas; Yu, Ga-Er; Leroux, Jean-Christophe

2007-07-01

Poly(ethylene oxide)-block-poly(styrene oxide) (PEO-b-PSO) and PEO-b-poly(butylene oxide) (PEO-b-PBO) of different chain lengths were synthesized and characterized for their self-assembling properties in water by dynamic/static light scattering, spectrofluorimetry, and transmission electron microscopy. The resulting polymeric micelles were evaluated for their ability to solubilize and protect the anticancer drug docetaxel (DCTX) from degradation. The drug release kinetics as well as the cytotoxicity of the loaded micelles were assessed in vitro. All polymers formed micelles with a highly viscous core at low critical association concentrations (<10 mg/L). Micelle morphology depended on the nature of the hydrophobic block, with PBO- and PSO-based micelles yielding monodisperse spherical and cylindrical nanosized aggregates, respectively. The maximum solubilization capacity for DCTX ranged from 0.7 to 4.2% and was the highest for PSO micelles exhibiting the longest hydrophobic segment. Despite their high affinity for DCTX, PEO-b-PSO micelles were not able to efficiently protect DCTX against hydrolysis under accelerated stability testing conditions. Only PEO-b-PBO bearing 24 BO units afforded significant protection against degradation. In vitro, DCTX was released slower from the latter micelles, but all formulations possessed a similar cytotoxic effect against PC-3 prostate cancer cells. These data suggest that PEO-b-P(SO/BO) micelles could be used as alternatives to conventional surfactants for the solubilization of taxanes.

Redox-sensitive Pluronic F127-tocopherol micelles: synthesis, characterization, and cytotoxicity evaluation

PubMed Central

Liu, Yuling; Fu, Sai; Lin, Longfei; Cao, Yuhong; Xie, Xi; Yu, Hua; Chen, Meiwan; Li, Hui

2017-01-01

Pluronic F127 (F127), an amphiphilic triblock copolymer, has been shown to have significant potential for drug delivery, as it is able to incorporate hydrophobic drugs and self-assemble into nanosize micelles. However, it suffers from dissociation upon dilution owing to the relatively high critical micelle concentration and lack of stimuli-responsive behavior. Here, we synthesized the α-tocopherol (TOC) modified F127 polymer (F127-SS-TOC) via a redox-sensitive disulfide bond between F127 and TOC, which formed stable micelles at relatively low critical micelle concentration and was sensitive to the intracellular redox environment. The particle size and zeta potential of the F127-SS-TOC micelles were 51.87±6.39 nm and -8.43±2.27 mV, respectively, and little changes in both particle size and zeta potential were observed within 7 days at room temperature. With 10 mM dithiothreitol stimulation, the F127-SS-TOC micelles rapidly dissociated followed by a significant change in size, which demonstrated a high reduction sensitivity of the micelles. In addition, the micelles showed a high hemocompatibility even at a high micelle concentration (1,000 μg/mL). Low cytotoxicity of the F127-SS-TOC micelles at concentrations ranging from 12.5 μg/mL to 200 μg/mL was also found on both Bel 7402 and L02 cells. Overall, our results demonstrated F127-SS-TOC micelles as a stable and safe aqueous formulation with a considerable potential for drug delivery. PMID:28435248

Effect of Micellization on the Adsorption Kinetics of Polymeric Surfactants to the Solid/Water Interface

NASA Astrophysics Data System (ADS)

Toomey, Ryan; Tirrell, Matthew

2002-03-01

We have studied the adsorption kinetics of two classes of hydrophobic/ionic diblock copolymer surfactants in aqueous environments to understand the role that micellization plays in the adsorption process. The two systems studied were poly(t-butyl styrene)-block-poly(styrene sulfonate) (PtBS-b-PSS) and polystyrene-block-poly(acrylic acid) (PS-b-PAA). It is found that by changing the hydrophobicity of the adsorbing surface, micelle adsorption can be turned on or off. When micelle adsorption occurs, the initial adsorption rate is always slower than the supply rate of micelles to the surface, indicating “reaction-limited” adsorption. Since these micelles have essentially frozen cores, the adsorption cannot be explained by the release of unimers from the micelles. Rather, micelles directly adsorb, and they have to overcome the potential barrier imposed by their corona. Due to micellization, the adsorption rate can also be a complex function of ionic strength. A regime was found where the initial adsorption rate decreased with increasing ionic strength. This anomaly can be explained by the onset of micellization. As the salt concentration is increased, more micelles are formed. However micelles adsorb roughly an order of magnitude slower than free chains. Therefore, if increasing the ionic strength produces more micelles, the adsorption rate will simultaneously decrease.

Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

NASA Astrophysics Data System (ADS)

Li, Xinru; Zhang, Yanhui; Fan, Yating; Zhou, Yanxia; Wang, Xiaoning; Fan, Chao; Liu, Yan; Zhang, Qiang

2011-12-01

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.

Examining the Roles of Emulsion Droplet Size and Surfactant in the Interfacial Instability-Based Fabrication Process of Micellar Nanocrystals

NASA Astrophysics Data System (ADS)

Sun, Yuxiang; Mei, Ling; Han, Ning; Ding, Xinyi; Yu, Caihao; Yang, Wenjuan; Ruan, Gang

2017-06-01

The interfacial instability process is an emerging general method to fabricate nanocrystal-encapsulated micelles (also called micellar nanocrystals) for biological detection, imaging, and therapy. The present work utilized fluorescent semiconductor nanocrystals (quantum dots or QDs) as the model nanocrystals to investigate the interfacial instability-based fabrication process of nanocrystal-encapsulated micelles. Our experimental results suggest intricate and intertwined roles of the emulsion droplet size and the surfactant poly (vinyl alcohol) (PVA) used in the fabrication process of QD-encapsulated poly (styrene-b-ethylene glycol) (PS-PEG) micelles. When no PVA is used, no emulsion droplet and thus no micelle is successfully formed; Emulsion droplets with large sizes ( 25 μm) result in two types of QD-encapsulated micelles, one of which is colloidally stable QD-encapsulated PS-PEG micelles while the other of which is colloidally unstable QD-encapsulated PVA micelles; In contrast, emulsion droplets with small sizes ( 3 μm or smaller) result in only colloidally stable QD-encapsulated PS-PEG micelles. The results obtained in this work not only help to optimize the quality of nanocrystal-encapsulated micelles prepared by the interfacial instability method for biological applications but also offer helpful new knowledge on the interfacial instability process in particular and self-assembly in general.

Phase Behavior of Salt-Free Polyelectrolyte Gel-Surfactant Systems.

PubMed

Andersson, Martin; Hansson, Per

2017-06-22

Ionic surfactants tend to collapse the outer parts of polyelectrolyte gels, forming shells that can be used to encapsulate other species including protein and peptide drugs. In this paper, the aqueous phase behavior of covalently cross-linked polyacrylate networks containing sodium ions and dodecyltrimethylammonium ions as counterions is investigated by means of swelling isotherms, dye staining, small-angle X-ray scattering, and confocal Raman spectroscopy. The equilibrium state is approached by letting the networks absorb pure water. With an increasing fraction of surfactant ions, the state of the water-saturated gels is found to change from being swollen and monophasic, via multiphasic states, to collapsed and monophasic. The multiphasic gels have a swollen, micelle-lean core surrounded by a collapsed, micelle-rich shell, or a collapsed phase forming a spheroidal inner shell separating two micelle-lean parts. It is shown that the transition between monophasic and core-shell states can be induced by variation of the osmotic pressure and variation of the charge of the micelles by forming mixed micelles with the nonionic surfactant octaethyleneglycol monododecylether. The experimental data are compared with theoretical predictions of a model derived earlier. In the calculations, the collapsed shell is assumed to be homogeneous, an approximation introduced here and shown to be excellent for a wide range of compositions. The theoretical results highlight the electrostatic and hydrophobic driving forces behind phase separation.

Disulphide bonds in casein micelle from milk.

PubMed

Bouguyon, Edwige; Beauvallet, Christian; Huet, Jean-Claude; Chanat, Eric

2006-05-05

Mammary epithelial cells synthesised and secreted caseins, the major milk proteins in most mammals, as large aggregates called micelles into the alveolar lumen they surround. We investigated the implication of the highly conserved cysteine(s) of kappa-casein in disulphide bond formation in casein micelles from several species. Dimers were found in all milks studied, confirming previous observation in ruminants. More importantly, the study of interchain disulphide bridges in mouse and rat casein micelles revealed that any casein possessing a cysteine is engaged in disulphide bond interchange; these species express four or five cysteine-containing caseins, respectively. We found that the main rodent caseins form both homo- and heterodimers. Additionally, disulphide bond formation among milk proteins was specific since the interaction of the caseins with cysteine-containing whey proteins was not observed in native casein micelles.

Polymeric micelles as a new drug carrier system and their required considerations for clinical trials.

PubMed

Yokoyama, Masayuki

2010-02-01

A polymeric micelle is a macromolecular assembly composed of an inner core and an outer shell, and most typically is formed from block copolymers. In the last two decades, polymeric micelles have been actively studied as a new type of drug carrier system, in particular for drug targeting of anticancer drugs to solid tumors. In this review, polymeric micelle drug carrier systems are discussed with a focus on toxicities of the polymeric micelle carrier systems and on pharmacological activities of the block copolymers. In the first section, the importance of the above-mentioned evaluation of these properties is explained, as this importance does not seem to be well recognized compared with the importance of targeting and enhanced pharmacological activity of drugs, particularly in the basic studies. Then, designs, types and classifications of the polymeric micelle system are briefly summarized and explained, followed by a detailed discussion regarding several examples of polymeric micelle carrier systems. Readers will gain a strategy of drug delivery with polymeric carriers as well as recent progress of the polymeric micelle carrier systems in their basic studies and clinical trials. The purpose of this review is to achieve tight connections between the basic studies and clinical trials.

Design of polymer conjugated 3-helix micelles as nanocarriers with tunable shapes.

PubMed

Ma, Dan; DeBenedictis, Elizabeth P; Lund, Reidar; Keten, Sinan

2016-11-24

Amphiphilic peptide-polymer conjugates have the ability to form stable nanoscale micelles, which show great promise for drug delivery and other applications. A recent design has utilized the end-conjugation of alkyl chains to 3-helix coiled coils to achieve amphiphilicity, combined with the side-chain conjugation of polyethylene glycol (PEG) to tune micelle size through entropic confinement forces. Here we investigate this phenomenon in depth, using coarse-grained dissipative particle dynamics (DPD) simulations in an explicit solvent and micelle theory. We analyze the conformations of PEG chains conjugated to three different positions on 3-helix bundle peptides to ascertain the degree of confinement upon assembly, as well as the ordering of the subunits making up the micelle. We discover that the micelle size and stability is dictated by a competition between the entropy of PEG chain conformations in the assembled state, as well as intermolecular cross-interactions among PEG chains that promote cohesion between neighboring conjugates. Our analyses build on the role of PEG molecular weight and conjugation site and lead to computational phase diagrams that can be used to design 3-helix micelles. This work opens pathways for the design of multifunctional micelles with tunable size, shape and stability.

Rennet-induced coagulation properties of yak casein micelles: A comparison with cow casein micelles.

PubMed

Zhang, Yan; Li, Yuan; Wang, Pengjie; Tian, Yanbao; Liang, Qi; Ren, Fazheng

2017-12-01

It is essential for yak cheese processing to understand the rennet-induced coagulation properties of gel formation from casein micelles. We have previously discovered that yak milk requires a longer incubation time but forms stronger gels compared with cow milk. In this study, we are aiming to understand the rennet-induced coagulation properties of yak casein micelles comparing with cow casein micelles. Rheological analyses revealed that the gelling times of yak and cow casein micelles were 11.6±0.5 and 8.7±0.4min (P<0.05) respectively, but yak casein gel had a higher elastic modulus G' (6.5±0.2Pa) than cow casein gel (2.5±0.2Pa; P<0.05). This is consistent with the results obtained by micro-rheology. Confocal laser scanning microscopic images (CLSM) and cryo-scanning electron microscopic images (cryo-SEM) showed that yak casein gel was more homogeneous and had smaller pore size than cow casein gels. Yak casein micelles had higher calcium (26.00mM), phosphate (19.90mM) and β-casein (relative 32%) concentrations. In addition, yak casein micelles were larger (Z-average 218.6nm) than cow casein micelles, and contained lower κ-casein (relative 13%). By comparison with cow casein micelles, yak casein micelle composition corresponding to their micellar calcium phosphate and κ-casein content may greatly contribute to the longer coagulation time and denser gel structure. An initial slower caseinomacropeptide (CMP) release rate and the slower rate of aggregation between para-casein micelles contributed to a more homogeneous yak gel network. Higher colloidal calcium phosphate is crucial for yak casein micelle aggregation and gel firmness because sufficient colloidal calcium phosphates can firmly glue sub-micelles and links casein micelles. This study provides valuable information for yak cheese production. Copyright © 2017. Published by Elsevier Ltd.

Disassembly and reassembly of amyloid fibrils in water-ethanol mixtures.

PubMed

Jordens, Sophia; Adamcik, Jozef; Amar-Yuli, Idit; Mezzenga, Raffaele

2011-01-10

This work presents the structural analysis of amyloid-like β-lactoglobulin fibrils incubated in ethanol-water mixtures after their formation in water. We observe for the first time the disassembly of semiflexible heat-denatured β-lactoglobulin fibrils and reassembly into highly flexible wormlike fibrils in ethanol-water solutions. Tapping mode atomic force microscopy is performed to follow structural changes. Our results show that in addition to their growth in length, there is a continuous nucleation process of new wormlike objects with time at the expense of the original β-lactoglobulin fibrils. The persistence length of wormlike fibrils (29.43 nm in the presence of 50% ethanol), indicative of their degree of flexibility, differs by 2 orders of magnitude from that of untreated β-lactoglobulin fibrils (2368.75 nm in pure water). Interestingly, wormlike fibrils do not exhibit a multiple strands nature like the pristine fibrils, as revealed by the lower maximum height and the lack of clear height periodicity along their contour length profile. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) demonstrates that the set of polypeptides obtained by ethanol degradation differs in some fractions from that present in pristine β-lactoglobulin fibrils. ATR-FTIR (attenuated total reflectance-Fourier transform infrared) spectroscopy also supports a different composition of the secondary structure of wormlike fibrils with a decreased amount of α-helix and increased random coils and turns content. These findings can contribute to deciphering the molecular mechanisms of protein aggregation into amyloid fibrils and their disassembly as well as enabling tailor-made production of protein fibrils.

Interactions in micellar solutions of β-casein

NASA Astrophysics Data System (ADS)

Leclerc, E.; Calmettes, P.

1997-02-01

β-casein is a protein which forms micelles in aqueous solvents. The magnitude and the range of the weight-average interactions between the diverse solute particles are infrared from small-angle neutron scattering measurements made on various β-casein solutions. Well above the critical micelle concentration (CMC), these interactions are repulsive. They weaken with decreasing protein concentration, and finally become strongly attractive near the CMC. Although indispensable for micelle formation this fact has never been reported so far.

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

NASA Astrophysics Data System (ADS)

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

2016-08-01

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.

Detergent effects on enzyme activity and solubilization of lipid bilayer membranes.

PubMed

Womack, M D; Kendall, D A; MacDonald, R C

1983-09-07

Over 50 detergents were tested to establish which would be most effective in releasing proteins from membrane-bounded compartments without denaturing them. Various concentrations each of detergent were tested for two activities: (1) solubilization of egg phospholipid liposomes as measured by reduction of turbidity and (2) effect of detergent concentration on the activities of soluble, hydrolytic enzymes. Those detergents most effective in solubilizing 0.2% lipid and least detrimental to enzymes were five pure, synthetic compounds recently introduced: CHAPS, CHAPSO, Zwittergents 310 and 312, and octylglucoside. Industrial detergents were generally much inferior, insofar as they solubilized membranes inefficiently and/or inactivated certain hydrolytic enzymes readily. The five detergents were characterized by (a) an unusually high critical micelle concentration and (b) a preference for forming mixed micelles with lipids instead of forming pure micelles, as indicated by an ability to solubilize lipid at concentrations of detergent significantly below the critical micelle concentration. This characteristic permits solubilization of high concentrations of membrane below the critical micelle concentration of the detergent so that protein denaturation is minimized. A generally applicable guideline that emerged from this study is that detergents should be used at approximately their critical micelle concentration which should not be exceeded by the concentration of membrane. Similar considerations should apply to the use of detergents in purifying and reconstituting intrinsic membrane proteins.

Rotational reorientation dynamics of Aerosol-OT reverse micelles formed in near-critical propane

DOE Office of Scientific and Technical Information (OSTI.GOV)

Heitz, M.P.; Bright, F.V.

1996-06-01

The rotational reorientation kinetics of two fluorescent solutes (rhodamine 6G, R6G, and rhodamine 101, R101) have been determined in sodium bis(2-ethylhexyl) sulfosuccinate (Aerosol-OT, AOT) reverse micelles formed in liquid and near-critical propane. We show that the amount of water loading ([water]/[AOT], R), continuous phase density, and temperature all influence the solute rotational dynamics. In all cases, the decay of anisotropy data (i.e., frequency-dependent differential polarized phase angle and polarized modulation ratio) are well described by a bi-exponential decay law. We find that the faster rotational correlation times are similar to but slightly less than the values predicted for an individualmore » AOT reverse micelle rotating in propane. The recovered rotational correlation times range from 200 to 500 ps depending on experimental conditions. This faster rotational process is explained in terms of lateral diffusion of the fluorophore along the water/headgroup interfacial region within the reverse micelle. The recovered values for the slower rotational correlation times range from 7 to 18 ns. These larger rotational reorientation times are assigned to varying micelle-micelle (i.e., tail-tail) interactions in the low-density, highly compressible fluid region. We also quantify the contribution of the reverse micellar {open_quotes}aggregate{close_quotes} to the total decay of anisotropy. {copyright} {ital 1996} {ital Society for Applied Spectroscopy}« less

Preclinical safety evaluation of intravenously administered mixed micelles.

PubMed

Teelmann, K; Schläppi, B; Schüpbach, M; Kistler, A

1984-01-01

Mixed micelles, with their main constituents lecithin and glycocholic acid, form a new principle for the parenteral administration of compounds which are poorly water-soluble. Their composition of mainly physiological substances as well as their comparatively good stability substantiate their attractivity in comparison to existing solvents. A decomposition due to physical influences such as heat or storage for several years will almost exclusively affect the lecithin component in the form of hydrolysis into free fatty acids and lysolecithin. Their toxicity was examined experimentally in various studies using both undecomposed and artificially decomposed mixed micelles. In these studies the mixed micelles were locally and systemically well tolerated and proved to be neither embryotoxic, teratogenic nor mutagenic. Only when comparatively high doses of the undecomposed mixed micelles were administered, corresponding to approximately 30 to 50 times the anticipated clinical injection volume (of e.g. diazepam mixed micelles), did some vomitus (dogs), slight liver enzyme elevation (rats and dogs), and slightly increased liver weights (dogs) occur. After repeated injections of the artificially decomposed formulation (approximately 25% of lecithin hydrolyzed to free fatty acids and lysolecithin) effects such as intravascular haemolysis, liver enzyme elevations and intrahepatic cholestasis (dogs only) were observed but only when doses exceeding a threshold of approximately 40 to 60 mg lysolecithin/kg body weight were administered. All alterations were reversible after cessation of treatment.

New shell crosslinked micelles from dextran with hydrophobic end groups and their interaction with bioactive molecules.

PubMed

Mocanu, Georgeta; Nichifor, Marieta; Stanciu, Magdalena C

2015-03-30

Micelles formed in aqueous solution by dextran with hydrophobic (alkyl) end-groups were stabilized through divinyl sulfone crosslinking of the dextran shell. The efficacy of the crosslinking reaction was influenced by the divinyl sulfone amount, the pH and micelle concentration. Crosslinked micelles with a moderate crosslinking degree were further functionalized by attachment of 10 and 17 moles% N-(2-hydroxypropyl)-N,N-dimethyl-N-benzylammonium chloride groups along the dextran chain. The size and shape of both crosslinked micelles and their cationic derivatives were analyzed by DLS and TEM. The prepared micelles were able to bind anionic diclofenac (60-370 mg/g), hydrophobic anionic indometacin (70-120 mg/g), and hydrophobic alpha-tocopherol (170-220 mg/g) or ergocalciferol (90-110 mg/g) by hydrophobic or/and electrostatic forces. The release experiments and the antioxidant activity of bound alpha-tocopherol highlighted the potential of the new nano-sized micelles mainly as carriers for prolonged and controlled delivery of hydrophobic drugs. Copyright © 2014 Elsevier Ltd. All rights reserved.

Nanoparticle Encapsulation in Diblock Copolymer/Homopolymer Blend Thin Film Mixtures

NASA Astrophysics Data System (ADS)

Zhao, Junnan; Chen, Xi; Green, Peter

2014-03-01

We investigated the organization of low concentrations of poly (2-vinylpyridine) (P2VP) grafted gold nanoparticles within a diblock copolymer polystyrene-b-poly (2-vinylpyridine) (PS-b-P2VP)/homopolymer polystyrene (PS) blend thin film. The PS-b-P2VP copolymers formed micelles, composed of inner cores of P2VP block and outer coronae of PS blocks, throughout the homopolymer PS. All nanoparticles were encapsulated within micelle cores and each micelle contained one or no nanoparticle, on average. When the host PS chains are much longer than corona chains, micelles tended to self-organize at the interfaces. Otherwise, they were dispersed throughout the PS host. In comparison to the neat PS-b-P2VP/PS blend, the nanoparticles/PS-b-P2VP/PS system had a higher density of smaller micelles, influenced largely by the number of nanoparticles in the system. The behavior of this system is understood in terms of the maximization of the nanoparticle/micelle core interactions and of the translational entropies of the micelles and the nanoparticles.

Crystallization-driven one-dimensional self-assembly of polyethylene-b-poly(tert-butylacrylate) diblock copolymers in DMF: effects of crystallization temperature and the corona-forming block.

PubMed

Fan, Bin; Liu, Lei; Li, Jun-Huan; Ke, Xi-Xian; Xu, Jun-Ting; Du, Bin-Yang; Fan, Zhi-Qiang

2016-01-07

Crystallization-driven self-assembly of polyethylene-b-poly(tert-butylacrylate) (PE-b-PtBA) block copolymers (BCPs) in N,N-dimethyl formamide (DMF) was studied. It is found that all three PE-b-PtBA BCPs used in this work can self-assemble into one-dimensional crystalline cylindrical micelles. When the BCP solution is cooled to crystallization temperature (Tc) from 130 °C, the seed micelles may be produced via two competitive processes in the initial period: stepwise micellization/crystallization and simultaneous crystallization/micellization. Subsequently, the seed micelles can undergo growth driven by the epitaxial crystallization of the unimers. The lengths of both the seed micelles and the grown micelles are longer for the BCP with a longer PtBA block at a higher Tc. Quasi-living growth of the PE-b-PtBA crystalline cylindrical micelles is achieved at a higher Tc. A longer PtBA block evidently retards the attachment of unimers to the crystalline micelles, leading to a slower growth rate.

Glycyrrhetinic Acid-Poly(ethylene glycol)-glycyrrhetinic Acid Tri-Block Conjugates Based Self-Assembled Micelles for Hepatic Targeted Delivery of Poorly Water Soluble Drug

PubMed Central

Xu, Ting; Liu, Chi; Chen, Can; Song, Xiangrong; Zheng, Yu

2013-01-01

The triblock 18β-glycyrrhetinic acid-poly(ethylene glycol)-18β-glycyrrhetinic acid conjugates (GA-PEG-GA) based self-assembled micelles were synthesized and characterized by FTIR, NMR, transmission electron microscopy, and particle size analysis. The GA-PEG-GA conjugates having the critical micelle concentration of 6 × 10−5 M were used to form nanosized micelles, with mean diameters of 159.21 ± 2.2 nm, and then paclitaxel (PTX) was incorporated into GA-PEG-GA micelles by self-assembly method. The physicochemical properties of the PTX loaded GA-PEG-GA micelles were evaluated including in vitro cellular uptake, cytotoxicity, drug release profile, and in vivo tissue distribution. The results demonstrate that the GA-PEG-GA micelles had low cytotoxicity and good ability of selectively delivering drug to hepatic cells in vitro and in vivo by the targeting moiety glycyrrhetinic acid. In conclusion, the GA-PEG-GA conjugates have potential medical applications for targeted delivery of poor soluble drug delivery. PMID:24376388

Complete regression of xenograft tumors using biodegradable mPEG-PLA-SN38 block copolymer micelles.

PubMed

Lu, Lu; Zheng, Yan; Weng, Shuqiang; Zhu, Wenwei; Chen, Jinhong; Zhang, Xiaomin; Lee, Robert J; Yu, Bo; Jia, Huliang; Qin, Lunxiu

2016-06-01

7-Ethyl-10-hydroxy-comptothecin (SN38) is an active metabolite of irinotecan (CPT-11) and the clinical application of SN38 is limited by its hydrophobicity and instability. To address these issues, a series of novel amphiphilic mPEG-PLA-SN38-conjugates were synthesized by linking SN38 to mPEG-PLA-SA, and they could form micelles by self-assembly. The effects of mPEG-PLA composition were studied in vitro and in vivo. The mean diameters of mPEG2K-PLA-SN38 micelles and mPEG4K-PLA-SN38 micelles were 10-20nm and 120nm, respectively, and mPEG2K-PLA-SN38 micelles showed greater antitumor efficacy than mPEG4K-PLA-SN38 micelles both in vitro and in vivo. These data suggest that the lengths of mPEG and PLA chains had a major impact on the physicochemical characteristics and antitumor activity of SN38-conjugate micelles. Copyright © 2016 Elsevier B.V. All rights reserved.

Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.

Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

Unraveling the Agglomeration Mechanism in Charged Block Copolymer and Surfactant Complexes

DOE PAGES

Borreguero, Jose M.; Pincus, Philip A.; Sumpter, Bobby G.; ...

2017-01-27

Here, we report a molecular dynamics simulation investigation of self-assembly and complex formation of charged-neutral double hydrophilic and hydrophobic-hydrophilic block copolymers (BCP) with oppositely charged surfactants. Furthermore, the structure of the surfactant micelles and the BCP aggregation on the micelle surface is systematically studied for five different BCP volume fractions that also mimics a reduction of the surfactant concentration. The local electrostatic interactions between the oppositely charged species encourage the formation of core-shell structures between the surfactant micelles where the surfactants form the cores and the charged blocks of the BCP form the corona. The emergent morphologies of these aggregatesmore » are contingent upon the nature of the BCP neutral blocks. The hydrophilic neutral blocks agglomerate with the micelles as hairy colloidal structures while the hydrophobic neutrals agglomerate in lamellar structures with the surfactant micelles. The distribution of counterion charges along the simulation box show a close-to-normal density distribution for the hydrophilic neutral blocks and a binodal distribution for hydrophobic neutral blocks. No specific surfactant concentration dependent scaling relation is observed as opposed to the simpler case of homo-polyelectrolytes.« less

CuS-Based Theranostic Micelles for NIR-Controlled Combination Chemotherapy and Photothermal Therapy and Photoacoustic Imaging.

PubMed

Chen, Guojun; Ma, Ben; Wang, Yuyuan; Xie, Ruosen; Li, Chun; Dou, Kefeng; Gong, Shaoqin

2017-12-06

Cancer remains a major threat to human health due to low therapeutic efficacies of currently available cancer treatment options. Nanotheranostics, capable of simultaneous therapy and diagnosis/monitoring of diseases, has attracted increasing amounts of attention, particularly for cancer treatment. In this study, CuS-based theranostic micelles capable of simultaneous combination chemotherapy and photothermal therapy (PTT), as well as photoacoustic imaging, were developed for targeted cancer therapy. The micelle was formed by a CuS nanoparticle (NP) functionalized by thermosensitive amphiphilic poly(acrylamide-acrylonitrile)-poly(ethylene glycol) block copolymers. CuS NPs under near-infrared (NIR) irradiation induced a significant temperature elevation, thereby enabling NIR-triggered PTT. Moreover, the hydrophobic core formed by poly(acrylamide-acrylonitrile) segments used for drug encapsulation exhibited an upper critical solution temperature (UCST; ∼38 °C), which underwent a hydrophobic-to-hydrophilic transition once the temperature rose above the UCST induced by NIR-irradiated CuS NPs, thereby triggering a rapid drug release and enabling NIR-controlled chemotherapy. The CuS-based micelles conjugated with GE11 peptides were tested in an epidermal growth factor receptor-overexpressing triple-negative breast cancer model. In both two-dimensional monolayer cell and three-dimensional multicellular tumor spheroid models, GE11-tagged CuS-based micelles under NIR irradiation, enabling the combination chemotherapy and PTT, exhibited the best therapeutic outcome due to a synergistic effect. These CuS-based micelles also displayed a good photoacoustic imaging ability under NIR illumination. Taken together, this multifunctional CuS-based micelle could be a promising nanoplatform for targeted cancer nanotheranostics.

Invited review: Caseins and the casein micelle: their biological functions, structures, and behavior in foods.

PubMed

Holt, C; Carver, J A; Ecroyd, H; Thorn, D C

2013-10-01

A typical casein micelle contains thousands of casein molecules, most of which form thermodynamically stable complexes with nanoclusters of amorphous calcium phosphate. Like many other unfolded proteins, caseins have an actual or potential tendency to assemble into toxic amyloid fibrils, particularly at the high concentrations found in milk. Fibrils do not form in milk because an alternative aggregation pathway is followed that results in formation of the casein micelle. As a result of forming micelles, nutritious milk can be secreted and stored without causing either pathological calcification or amyloidosis of the mother's mammary tissue. The ability to sequester nanoclusters of amorphous calcium phosphate in a stable complex is not unique to caseins. It has been demonstrated using a number of noncasein secreted phosphoproteins and may be of general physiological importance in preventing calcification of other biofluids and soft tissues. Thus, competent noncasein phosphoproteins have similar patterns of phosphorylation and the same type of flexible, unfolded conformation as caseins. The ability to suppress amyloid fibril formation by forming an alternative amorphous aggregate is also not unique to caseins and underlies the action of molecular chaperones such as the small heat-shock proteins. The open structure of the protein matrix of casein micelles is fragile and easily perturbed by changes in its environment. Perturbations can cause the polypeptide chains to segregate into regions of greater and lesser density. As a result, the reliable determination of the native structure of casein micelles continues to be extremely challenging. The biological functions of caseins, such as their chaperone activity, are determined by their composition and flexible conformation and by how the casein polypeptide chains interact with each other. These same properties determine how caseins behave in the manufacture of many dairy products and how they can be used as functional ingredients in other foods. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

pH-induced vesicle-to-micelle transition in amphiphilic diblock copolymer: investigation by energy transfer between in situ formed polymer embedded gold nanoparticles and fluorescent dye.

PubMed

Maiti, Chiranjit; Banerjee, Rakesh; Maiti, Saikat; Dhara, Dibakar

2015-01-01

The ability to regulate the formation of nanostructures through self-assembly of amphiphilic block copolymers is of immense significance in the field of biology and medicine. In this work, a new block copolymer synthesized by using reversible addition-fragmentation chain transfer (RAFT) polymerization technique from poly(ethylene glycol) monomethyl ether acrylate (PEGMA) and Boc-l-tryptophan acryloyloxyethyl ester (Boc-l-trp-HEA) was found to spontaneously form pH-responsive water-soluble nanostructures after removal of the Boc group. While polymer vesicles or polymerosomes were formed at physiological pH, the micelles were formed at acidic pH (< 5.2), and this facilitated a pH-induced reversible vesicle-to-micelle transition. Formation of these nanostructures was confirmed by different characterization techniques, viz. transmission electron microscopy, dynamic light scattering, and steady-state fluorescence measurements. Further, these vesicles were successfully utilized to reduce HAuCl4 and stabilize the resulting gold nanoparticles (AuNPs). These AuNPs, confined within the hydrophobic shell of the vesicles, could participate in energy transfer process with fluorescent dye molecules encapsulated in the core of the vesicles, thus forming a nanometal surface energy transfer (NSET) pair. Subsequently, following the efficiency of energy transfer between this pair, it was possible to monitor the process of transition from vesicles to micelles. Thus, in this work, we have successfully demonstrated that NSET can be used to follow the transition between nanostructures formed by amphiphilic block copolymers.

Block Copolymer Micelles as Nanocontainers for Controlled Release of Proteins from Biocompatible Oil Phases

PubMed Central

2009-01-01

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(ϵ-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. PMID:19235932

E-selectin-targeted Sialic Acid-PEG-dexamethasone Micelles for Enhanced Anti-Inflammatory Efficacy for Acute Kidney Injury.

PubMed

Hu, Jing-Bo; Kang, Xu-Qi; Liang, Jing; Wang, Xiao-Juan; Xu, Xiao-Ling; Yang, Ping; Ying, Xiao-Ying; Jiang, Sai-Ping; Du, Yong-Zhong

2017-01-01

The effective treatment for acute kidney injury (AKI) is currently limited, and care is primarily supportive. Sialic acid (SA) is main component of Sialyl Lewis x antigen on the mammalian cell surface, which participates in E-selectin binding. Therefore, dexamethasone(DXM)-loaded E-selectin-targeting sialic acid-polyethylene glycol-dexamethasone (SA-PEG-DXM/DXM) conjugate micelles are designed for ameliorating AKI. The conjugates are synthesized via the esterification reaction between PEG and SA or DXM, and can spontaneously form micelles in an aqueous solution with a 65.6 µg/mL critical micelle concentration. Free DXM is incorporated into the micelles with 6.28 ± 0.21% drug loading content. In vitro DXM release from SA-PEG-DXM/DXM micelles can be prolonged to 48h. Much more SA-PEG-DXM micelles can be internalized by lipopolysaccharide (LPS)-activated human umbilical vein endothelial cells (HUVECs) in comparison to PEG-DXM micelles due to specific interaction between SA and E-selectin expressed on HUVECs, and consequently more SA-PEG-DXM micelles are accumulated in the kidney of AKI murine model. Furthermore, SA in SA-PEG-DXM conjugates can significantly ameliorate LPS-induced production of pro-inflammatory cytokines via suppressing LPS-activated Beclin-1/Atg5-Atg12-mediated autophagy to attenuate toxicity. Compared with free DXM and PEG-DXM/DXM micelles, SA-PEG-DXM/DXM micelles show better therapeutical effects, as reflected by the improved renal function, histopathological changes, pro-inflammatory cytokines, oxidative stress and expression of apoptotic related proteins.

Cationic micelles self-assembled from cholesterol-conjugated oligopeptides as an efficient gene delivery vector.

PubMed

Guo, Xin Dong; Tandiono, Fanny; Wiradharma, Nikken; Khor, Dingyue; Tan, Chuan Guan; Khan, Majad; Qian, Yu; Yang, Yi-Yan

2008-12-01

Cholesterol-conjugated H(5)R(10) and H(10)R(10) oligopeptides (HR15-Chol and HR20-Chol) were designed and synthesized. These amphiphilic oligopeptides were able to self-assemble into cationic micelles in aqueous solution at low concentrations, and their critical micelle concentrations in sodium acetate buffer (20mM, pH 5.0) were 17.8 and 28.2mg/L respectively. The micelle formation was further evidenced via SEM and dynamic light scattering analyses. The average hydrodynamic size of HR15-Chol and HR20-Chol micelles was about 425 and 435 nM in diameter with zeta potential of 64 and 66 mV respectively. The formation of micelles increased local concentration of cationic charge, leading to higher DNA binding efficiency as compared to the control peptides HR15 and HR20. The minimum size observed for HR15-Chol/DNA and HR20-Chol/DNA complexes was about 175-176 nM, and the maximum zeta potential was around 61-62 mV. In comparison, HR15 and HR20 formed DNA complexes with a similar size but significantly lower zeta potential (i.e. about 31-40 mV). In particular, after being challenged by DMEM medium, the size of peptide/DNA complexes was increased significantly and their surface charge was neutralized. Nevertheless, the size of the micelle/DNA complexes formed from HR15-Chol and HR20-Chol was still about 200 nM with positive charge of around 20 mV at high N/P ratios. The micelles induced much higher overall gene expression (i.e. luciferase expression) levels than the peptides in both HepG2 and HEK293 cell lines. Increasing the histidine residue from 0 to 5 to 10 further increased gene expression efficiency. In particular, HR20-Chol micelles yielded 95% GFP-positive HepG2 cells at N/P 50, much higher than that induced by PEI at its optimal N/P ratio (i.e. 10), which was 6.8%. In 4T1 cells, HR20-Chol induced 2 times higher luciferase expression level than PEI at their optimal N/P ratios. Moreover, HR20-Chol micelle/DNA complexes were less cytotoxic than PEI/DNA complexes. These micelles may be a promising carrier for delivery of therapeutic genes.

Thermoresponsiveness of hybrid micelles from poly(ethylene glycol)-block-poly(4-vinylpyridium) cations and SO4(2-) anions in aqueous solutions.

PubMed

Wu, Kai; Shi, Linqi; Zhang, Wangqing; An, Yingli; Zhang, Xu; Li, Zhanyong; Zhu, X X

2006-02-14

The SO4(2-)-induced micellization of poly(ethylene glycol)-block-poly(4-vinylpyridium) (PEG110-b-P(4-VPH+)35) and the thermoresponsiveness of these hybrid micelles are studied by dynamic and static light scattering. When the concentration of H2SO4 is high enough, PEG110-b-P(4-VPH+)35 forms stable hybrid micelles with an ionic core of P(4-VPH+)35/SO4(2-) and a PEG corona at 25 degrees C. The formation of the hybrid micelles is reversible. A thermodynamic equilibrium exists between the hybrid micelles and PEG110-b-P(4-VPH+)35 unimers. The shifts of the equilibrium are mainly attributed to the variation of the electrostatic energy and entropic energy of the system. Therefore, the temperature can determine the states of the equilibrium, which means that the dissociation or the formation of the hybrid micelles can be triggered by just varying the temperature.

High pressure-assisted encapsulation of vitamin D2 in reassembled casein micelles

NASA Astrophysics Data System (ADS)

Menéndez-Aguirre, O.; Stuetz, W.; Grune, T.; Kessler, A.; Weiss, J.; Hinrichs, J.

2011-03-01

For the encapsulation of vitamin D2, native casein micelles and vitamin D2 with or without additional Ca2+-Pi were treated at 600 MPa and 37 °C for 60 min. The pressure release rate was set at 20 or 600 MPa/min. Vitamin D2 was quantified by reversed-phase high-performance liquid chromatography, and physical properties of the micelles were analysed by photon correlation spectroscopy. The results demonstrate that simultaneous application of Ca2+-Pi and high pressure treatment with a fast release rate significantly increased loading of vitamin D2 per casein by 6.9-fold. The addition of Ca2+-Pi enhanced micelle aggregation and the vitamin was entrapped within the formed aggregates. However, high pressure treatment without Ca2+-Pi with a slow pressure release rate revealed similar results, increasing vitamin D2 per casein by 6.7-fold. The vitamin D2 loading in reassembled casein micelles is supposed to be due to hydrophobic interactions between the hydrophobic domains of the micelles.

Polysaccharide-Based Micelles for Drug Delivery

PubMed Central

Zhang, Nan; Wardwell, Patricia R.; Bader, Rebecca A.

2013-01-01

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. PMID:24300453

Structural changes of casein micelles in a calcium gradient film.

PubMed

Gebhardt, Ronald; Burghammer, Manfred; Riekel, Christian; Roth, Stephan Volkher; Müller-Buschbaum, Peter

2008-04-09

Calcium gradients are prepared by sequentially filling a micropipette with casein solutions of varying calcium concentration and spreading them on glass slides. The casein film is formed by a solution casting process, which results in a macroscopically rough surface. Microbeam grazing incidence small-angle X-ray scattering (microGISAXS) is used to investigate the lateral size distribution of three main components in casein films: casein micelles, casein mini-micelles, and micellar calcium phosphate. At length scales within the beam size the film surface is flat and detection of size distribution in a macroscopic casein gradient becomes accessible. The model used to analyze the data is based on a set of three log-normal distributed particle sizes. Increasing calcium concentration causes a decrease in casein micelle diameter while the size of casein mini-micelles increases and micellar calcium phosphate particles remain unchanged.

A pH and redox dual stimuli-responsive poly(amino acid) derivative for controlled drug release.

PubMed

Gong, Chu; Shan, Meng; Li, Bingqiang; Wu, Guolin

2016-10-01

A pH and redox dual stimuli-responsive poly(aspartic acid) derivative for controlled drug release was successfully developed through progressive ring-opening reactions of polysuccinimide (PSI). Polyethylene glycol (PEG) chains were grafted onto the polyaspartamide backbone via redox-responsive disulfide linkages, providing a sheddable shell for the polymeric micelles in a reductive environment. Phenyl groups were introduced into the polyaspartamide backbone via the aminolysis reaction of PSI to serve as the hydrophobic segment of micelles. The polyaspartamide scaffold was also functionalized with N-(3-aminopropyl)-imidazole to obtain the pH-responsiveness manifesting as a swelling of the core of micelles at a low pH. The polymeric micelles with a core-shell nanostructure forming in neutral media exhibited both pH and redox responsive characteristics. Doxorubicin (DOX) as a model drug was encapsulated into the core of micelles through both hydrophobic and π-π interactions between aromatic rings and the DOX-loaded polymeric micelles exhibited accelerated drug release behaviors in an acidic and reductive environment due to the swelling of hydrophobic cores and the shedding of PEG shells. Furthermore, the cytocompability of the polymer and the cytotoxicity of DOX-loaded micelles towards Hela cells under corresponding conditions were evaluated, and the endocytosis of DOX-loaded polymeric micelles and the intracellular drug release from micelles were observed. All obtained data indicated that the micelle was a promising candidate for controlled drug release. Copyright © 2016 Elsevier B.V. All rights reserved.

Stabilized micelles of amphoteric polyurethane formed by thermoresponsive micellization in HCl aqueous solution.

PubMed

Qiao, Yong; Zhang, Shifeng; Lin, Ouya; Deng, Liandong; Dong, Anjie

2008-04-01

The thermoresponsive micellization behavior of amphoteric polyurethane (APU) was studied in HCl aqueous solution (pH 2.0) through light scattering, transmission electron microscopy, and fluorescent measurement. When APU concentration is high enough, nonreversible assembly of macromolecules can be observed with temperature decreasing from 25 to 4 degrees C. However, micelles reaching equilibrium at 4 degrees C can self-assemble reversibly in the temperature range of 4-55 degrees C. According to our research, we found it is the temperature sensitivity of the poly(propylene oxide) (PPO) segments that leads to the reassembly of APU at lower temperature. We proposed that core-shell-corona micelles ultimately form with hydrophobic core, PPO shell, and hydrophilic corona when temperature increases from 4 to 25 degrees C. This structure is very stable and does not change at higher temperatures (25-55 degrees C). That provides a new way to obtain stable micelles with small size and narrow size distribution at higher concentration of APU.

Supramolecular Complexes Formed in Systems Bile Salt-Bilirubin-Silica

NASA Astrophysics Data System (ADS)

Vlasova, N. N.; Severinovskaya, O. V.; Golovkova, L. P.

The formation of supramolecular complexes between bilirubin and primary micelles of bile salts has been studied. The association constants of bile salts and binding of bilirubin with these associates have been determined. The adsorption of bilirubin and bile salts from individual and mixed aqueous solutions onto hydrophobic silica surfaces has been investigated. The interaction of bilirubin with primary bile salt micelles and the strong retention in mixed micelles, which are supramolecular complexes, result in the adsorption of bilirubin in free state only.

Salt-Induced Block Copolymer Micelles as Nanoreactors for the Formation of CdS Nanoparticles

DTIC Science & Technology

2001-11-01

or corona of micelles is presented. Poly(styrene-block-2-vinylpyridine) ( PS - b - P2VP ) and cadmium ions form aggregates of single micelles, called...ratio and block copolymer concentration in THF etc. EXPERIMENTAL DETAILS The synthesis of the PS - b - P2VP block copolymer was performed using sequential...nanoparticles: PS - b - P2VP block copolymer was dissolved in THF at different concentrations under vigorous stirring for 1 hour. Cd(Ac)2.2H 20 dissolved in a

Fabrication and study of properties of magnetite nanoparticles in hybrid micelles of polystyrene-block-polyethylene oxide and sodium dodecyl sulfate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loginova, T. P., E-mail: tlg@ineos.ac.ru; Timofeeva, G. I.; Lependina, O. L.

2016-01-15

Magnetite nanoparticles have been formed for the first time in hybrid micelles of polystyrene-block-polyethylene oxide and sodium dodecyl sulfate in water by ultrasonic treatment at room temperature. An analysis by small-angle X-ray scattering and transmission electron microscopy (TEM) showed that magnetite nanoparticles in hybrid micelles of block copolymer and sodium dodecyl sulfate are polydesperse (have sizes from 0.5 to 20 nm). The specific magnetization of solid samples has been measured.

pH-responsive unimolecular micelle-gold nanoparticles-drug nanohybrid system for cancer theranostics.

PubMed

Lin, Wenjing; Yao, Na; Qian, Long; Zhang, Xiaofang; Chen, Quan; Wang, Jufang; Zhang, Lijuan

2017-08-01

The development of an in situ formed pH-responsive theranostic nanocomposite for anticancer drug delivery and computed tomography (CT) imaging was reported. β-cyclodextrin-{poly(lactide)-poly(2-(dimethylamino) ethyl methacrylate)-poly[oligo(2-ethyl-2-oxazoline)methacrylate]} 21 [β-CD-(PLA-PDMAEMA-PEtOxMA) 21 ] unimolecular micelles served as a template for the in situ formation of gold nanoparticles (GNPs) and the subsequent encapsulation of doxorubicin (DOX). The formation of unimolecular micelles, microstructures and the distributions of GNPs and DOX were investigated through the combination of experiments and dissipative particle dynamics (DPD) simulations. β-CD-(PLA-PDMAEMA-PEtOxMA) 21 formed spherical unimolecular micelles in aqueous solution within a certain range of polymer concentrations. GNPs preferentially distributed in the PDMAEMA area. The maximum wavelength (λ max ) and the size of GNPs increased with increasing concentration of HAuCl 4 . DOX preferentially distributed in the PDMAEMA mesosphere, but penetrated the inner PLA core with increasing DOX concentration. DOX-loaded micelles with 41-61% entrapment efficiency showed fast release (88% after 102h) under acidic tumor conditions. Both in vitro and in vivo experiments revealed superior anticancer efficacy and effective CT imaging properties for β-CD-(PLA-PDMAEMA-PEtOxMA) 21 /Au/DOX. We conclude that the reported unimolecular micelles represent a class of versatile smart nanocarriers for theranostic application. Developing polymeric nanoplatforms as integrated theranostic vehicles for improving cancer diagnostics and therapy is an emerging field of much importance. This article aims to develop an in situ formed pH-responsive theranostic nanocomposite for anticancer drug delivery and computed tomography (CT) imaging. Specific emphases is on structure-properties relationship. There is a sea of literature on polymeric drug nanocarriers, and a couple of polymer-stabilized gold nanoparticles (GNPs) systems for cancer diagnosis are also known. However, to our knowledge, there has been no report on polymeric unimolecular micelles capable of dual loading of GNPs without external reducing agents and anticancer drugs for cancer diagnosis and treatment. To this end, the target of the current work was to develop an in situ formed nanocarrier, which actively dual wrapped CT contrast agent GNPs and hydrophobic anticancer drug doxorubicin (DOX), achieving high CT imaging and antitumor efficacy under in vitro and in vivo acid tumor condition. Meanwhile, by taking advantage of dissipative particle dynamics (DPD) simulation, we further obtained the formation process and mechanism of unimolecular micelles, and detailed distributions and microstructures of GNPs and DOX on unimolecular micelles. Taken together, our results here provide insight and guidance for the design of more effective nanocarriers for cancer theranostic application. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Novel micelle formulation of curcumin for enhancing antitumor activity and inhibiting colorectal cancer stem cells

PubMed Central

Wang, Ke; Zhang, Tao; Liu, Lina; Wang, Xiaolei; Wu, Ping; Chen, Zhigang; Ni, Chao; Zhang, Junshu; Hu, Fuqiang; Huang, Jian

2012-01-01

Background 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. PMID:22927762

Multifunctional SPIO/DOX-loaded A54 Homing Peptide Functionalized Dextran-g-PLGA Micelles for Tumor Therapy and MR Imaging

NASA Astrophysics Data System (ADS)

Situ, Jun-Qing; Wang, Xiao-Juan; Zhu, Xiu-Liang; Xu, Xiao-Ling; Kang, Xu-Qi; Hu, Jing-Bo; Lu, Chen-Ying; Ying, Xiao-Ying; Yu, Ri-Sheng; You, Jian; Du, Yong-Zhong

2016-10-01

Specific delivery of chemotherapy drugs and magnetic resonance imaging (MRI) contrast agent into tumor cells is one of the issues to highly efficient tumor targeting therapy and magnetic resonance imaging. Here, A54 peptide-functionalized poly(lactic-co-glycolic acid)-grafted dextran (A54-Dex-PLGA) was synthesized. The synthesized A54-Dex-PLGA could self-assemble to form micelles with a low critical micelle concentration of 22.51 μg. mL-1 and diameter of about 50 nm. The synthetic A54-Dex-PLGA micelles can encapsulate doxorubicin (DOX) as a model anti-tumor drug and superparamagnetic iron oxide (SPIO) as a contrast agent for MRI. The drug-encapsulation efficiency was about 80% and the in vitro DOX release was prolonged to 72 hours. The DOX/SPIO-loaded micelles could specifically target BEL-7402 cell line. In vitro MRI results also proved the specific binding ability of A54-Dex-PLGA/DOX/SPIO micelles to hepatoma cell BEL-7402. The in vivo MR imaging experiments using a BEL-7402 orthotopic implantation model further validated the targeting effect of DOX/SPIO-loaded micelles. In vitro and in vivo anti-tumor activities results showed that A54-Dex-PLGA/DOX/SPIO micelles revealed better therapeutic effects compared with Dex-PLGA/DOX/SPIO micelles and reduced toxicity compared with commercial adriamycin injection.

The importance of nanoparticle shape in cancer drug delivery.

PubMed

Truong, Nghia P; Whittaker, Michael R; Mak, Catherine W; Davis, Thomas P

2015-01-01

Nanoparticles have been successfully used for cancer drug delivery since 1995. In the design of commercial nanoparticles, size and surface characteristics have been exploited to achieve efficacious delivery. However, the design of optimized drug delivery platforms for efficient delivery to disease sites with minimal off-target effects remains a major research goal. One crucial element of nanoparticle design influencing both pharmacokinetics and cell uptake is nanoparticle morphology (both size and shape). In this succinct review, the authors collate the recent literature to assess the current state of understanding of the influence of nanoparticle shape on the effectiveness of drug delivery with a special emphasis on cancer therapy. This review draws on studies that have focused on the role of nonspherical nanoparticles used for cancer drug delivery. In particular, the authors summarize the influence of nanoparticle shape on biocirculation, biodistribution, cellular uptake and overall drug efficacy. By comparing spherical and nonspherical nanoparticles, they establish some general design principles to serve as guidelines for developing the next generation of nanocarriers for drug delivery. Pioneering studies on nanoparticles show that nonspherical shapes show great promise as cancer drug delivery vectors. Filamentous or worm-like micelles together with other rare morphologies such as needles or disks may become the norm for next-generation drug carriers, though at present, traditional spherical micelles remain the dominant shape of nanocarriers described in the literature due to synthesis and testing difficulties. The few reports that do exist describing nonspherical nanoparticles show a number of favorable properties that should encourage more efforts to develop facile and versatile nanoparticle synthesis methodologies with the flexibility to create different shapes, tunable sizes and adaptable surface chemistries. In addition, the authors note that there is a current lack of understanding into the factors governing (and optimizing) the inter-relationships of size, surface characteristics and shapes of many nanoparticles proposed for use in cancer therapy.

Tannin-assisted aggregation of natively unfolded proteins

NASA Astrophysics Data System (ADS)

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

2008-06-01

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.

Structure and stabilizing interactions of casein micelles probed by high-pressure light scattering and FTIR.

PubMed

Gebhardt, Ronald; Takeda, Naohiro; Kulozik, Ulrich; Doster, Wolfgang

2011-03-17

Caseins form heterogeneous micelles composed of three types of disordered protein chains (α, β, κ), which include protein-bound calcium phosphate particles. We probe the stability limits of the micelle by applying hydrostatic pressure. The resulting changes of the size distribution and the average molecular weight are recorded in situ with static and dynamic light scattering. Pressure induces irreversible dissociation of the micelles into monomers above a critical value depending on their size. The critical pressure increases with temperature, pH, and calcium concentration due to the interplay of hydrophobic and electrostatic interactions. The pressure transition curves are biphasic, reflecting the equilibrium of two micelle states with different stability, average size, entropy, and calcium bound. The fast process of pressure dissociation is used to probe the slow equilibrium of the two micelle states under various conditions. Binding and release of β-casein from the micelle is suggested as the molecular mechanism of stabilization associated with the two states. In situ FTIR spectroscopy covering the P-O stretching region indicates that bound calcium phosphate particles are released from serine phosphate residues at pressures above 100 MPa. The resulting imbalance of charge triggers the complete decomposition of the micelle. © 2011 American Chemical Society

Tuning Structural Properties of Biocompatible Block Copolymer Micelles by Varying Solvent Composition

NASA Astrophysics Data System (ADS)

Cooksey, Tyler; Singh, Avantika; Mai Le, Kim; Wang, Shu; Kelley, Elizabeth; He, Lilin; Vajjala Kesava, Sameer; Gomez, Enrique; Kidd, Bryce; Madsen, Louis; Robertson, Megan

The self-assembly of block copolymers into micelles when introduced to selective solvents enables a wide array of applications, ranging from drug delivery to personal care products to nanoreactors. In order to probe the assembly and dynamics of micellar systems, the structural properties and solvent uptake of biocompatible poly(ethylene oxide-b- ɛ-caprolactone) (PEO-PCL) diblock copolymers in deuterated water (D2O) / tetrahydrofuran (THFd8) mixtures were investigated using small-angle neutron scattering in combination with nuclear magnetic resonance. PEO-PCL block copolymers, of varying molecular weight yet constant block ratio, formed spherical micelles through a wide range of solvent compositions. Varying the composition from 10 to 60 % by volume THFd8\\ in D2O / THFd8 mixtures was a means of varying the core-corona interfacial tension in the micelle system. An increase in THFd8 content in the bulk solvent increased the solvent uptake within the micelle core, which was comparable for the two series, irrespective of the polymer molecular weight. Differences in the behaviors of the micelle size parameters as the solvent composition varied originated from the differing trends in aggregation number for the two micelle series. Incorporation of the known unimer content determined from NMR allowed refinement of extracted micelle parameters.

A symmetrical method to obtain shear moduli from microrheology† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sm02499a

PubMed Central

Nishi, Kengo

2018-01-01

Passive microrheology typically deduces shear elastic loss and storage moduli from displacement time series or mean-squared displacements (MSD) of thermally fluctuating probe particles in equilibrium materials. Common data analysis methods use either Kramers–Kronig (KK) transformation or functional fitting to calculate frequency-dependent loss and storage moduli. We propose a new analysis method for passive microrheology that avoids the limitations of both of these approaches. In this method, we determine both real and imaginary components of the complex, frequency-dependent response function χ(ω) = χ′(ω) + iχ′′(ω) as direct integral transforms of the MSD of thermal particle motion. This procedure significantly improves the high-frequency fidelity of χ(ω) relative to the use of KK transformation, which has been shown to lead to artifacts in χ′(ω). We test our method on both model and experimental data. Experiments were performed on solutions of worm-like micelles and dilute collagen solutions. While the present method agrees well with established KK-based methods at low frequencies, we demonstrate significant improvement at high frequencies using our symmetric analysis method, up to almost the fundamental Nyquist limit. PMID:29611576

Antitumor effects of hydroxycamptothecin-loaded poly[ethylene glycol]-poly [gamma-benzyl-L-glutamate] micelles against oral squamous cell carcinoma.

PubMed

Ding, Xue-Qiang; Chen, Dan; Wang, An-Xun; Li, Su; Chen, Yu; Wang, Ji

2007-01-01

Therapeutic use of hydroxycamptothecin (HCPT), a promising antitumor agent, is limited by its poor solubility and rapid destruction. Amphiphilic block copolymer micelle carriers possess significant potential for improving drug solubility and stability. Poly[ethylene glycol]-poly[gamma-benzyl-L-glutamate] (PEG-PBLG) micelles were prepared and loaded with the active lactone form of HCPT using an uncomplicated dialysis method. HPLC and scanning electron microscopy studies revealed an encapsulation efficiency of 56.8% and a core-shell figure with a mean diameter of 200 nm. Encapsulated HCPT lactone was compared with the less active, open ring-carboxylated HCPT-Na+ soluble form generated in vivo from the free active lactone for activity against oral squamous cell carcinoma. Cytotoxicity in vitro was measured in cultured Tca8113 cells by the MTT assay and microscopy techniques. The golden hamster cheek pouch squamous cell carcinoma model was employed for in vivo studies; encapsulated lactone and open ring-carboxylated forms of HCPT were administered intraperitoneally, followed by determinations of tumor growth rate and inhibition ratio. PEG-PBLG micelles were not cytotoxic in vitro. At 48 h of treatment, open ring-carboxylated HCPT proved significantly more cytotoxic in vitro than encapsulated HCPT lactone. At 96 h, however, the open ring-carboxylated and encapsulated drugs displayed comparable in vitro cytotoxicities. In the in vivo squamous cell carcinoma model, encapsulated HCPT lactone produced greater and more prolonged tumor suppression compared to the open ring-carboxylated form. The antitumor effects of HCPT/PEG-PBLG micelles against oral squamous cell carcinoma in vivo are concluded to be superior to those exerted by open ring-carboxylated HCPT.

Monte Carlo and mean-field studies of phase evolution in concentrated surfactant solutions

NASA Astrophysics Data System (ADS)

Bohbot, Yardena; Ben-Shaul, Avinoam; Granek, Rony; Gelbart, William M.

1995-11-01

A two-dimensional lattice model, originally introduced by Granek et al. [J. Chem. Phys. 101, 4331 (1994)], is used to demonstrate the intricate coupling between the intramicellar interactions that determine the optimal aggregation geometry of surfactant molecules in dilute solution, and the intermicellar interactions that govern the phase behavior at higher concentrations. Three very different scenarios of self-assembly and phase evolution are analyzed in detail, based on Monte Carlo studies and theoretical interpretations involving mean-field, Landau-Ginzburg, Bethe-Peierls, and virial expansion schemes. The basic particles in the model are ``unit micelles'' which, due to spontaneous self-assembly or because of excluded area interactions, can fuse to form larger aggregates. These aggregates are envisaged as flat micelles composed of a bilayerlike body surrounded by a curved semitoroidal rim. The system's Hamiltonian involves one- through four-body potentials between the unit micelles, which account for their tendency to form aggregates of different shapes, e.g., elongated vs disklike micelles. Equivalently, the configurational energy of the system is a sum of micellar self-energies involving the packing free energies of the constituent molecules in the bilayer body and in rim segments of different local curvature. The rim energy is a sum of a line tension term and a 1D curvature energy which depends on the rim spontaneous curvature and bending rigidity. Different combinations of these molecular parameters imply different optimal packing geometries and hence different self-assembly and phase behaviors. The emphasis in this paper is on systems of ``curvature loving'' amphiphiles which, in our model, are characterized by negative line tension. The three systems studied are: (i) A dilute solution of stable disklike micelles which, upon increasing the concentration, undergoes a first-order phase transition to a continuous bilayer with isolated hole defects. An intermediate modulated ``checkerboard'' phase appears under certain conditions at low temperatures. (ii) A system of unit micelles which in dilute solution tend to associate into linear micelles. These micelles are rodlike at low temperatures, becoming increasingly more flexible as the temperature increases. Upon increasing the concentration the micelles grow and undergo (in 2D) a continuous transition into nematic and ``stripe'' phases of long rods. At still higher concentrations the micellar stripes fuse into continuous sheets with line defects. (iii) A system in which, already in dilute solution, the micelles favor the formation of branched aggregates, analogous to the branched cylindrical micelles recently observed in certain surfactant solutions. As the concentration increases the micelles associate into networks (``gels'') composed of a mesh of linear micelles linked by ``T-like'' intermicellar junctions. The network may span the entire system or phase separate and coexist with a dilute micellar phase, depending on the details of the molecular packing parameters.

Multiscale Molecular Dynamics Simulations of Model Hydrophobically Modified Ethylene Oxide Urethane Micelles.

PubMed

Yuan, Fang; Larson, Ronald G

2015-09-24

The flower-like micelles of various aggregation numbers of a model hydrophobically modified ethylene oxide urethane (HEUR) molecule, C16E45C16, and their corresponding starlike micelles, containing the surfactants C16E22 and C16E23, were studied by atomistic and coarse-grained molecular dynamic (MD) simulations. We used free energies from umbrella sampling to calculate the size distribution of micelle sizes and the average time for escape of a hydrophobic group from the micelle. Using the coarse-grained MARTINI force field, the most probable size of the model HEUR molecule was thereby determined to be about 80 hydrophobes per micelle and the average hydrophobe escape time to be about 0.1 s, both of which are consistent with previous experimental studies. Atomistic simulations reveal that hydrogen bond formation and the mean lifetime of hydration waters of the poly(ethylene oxide) (or PEO) groups are location-dependent in the HEUR micelle, with PEO groups immediately adjacent to the C16 groups forming the fewest hydrogen bonds with water and having hydration waters with longer lifetimes than those of the PEO groups located further away from the C16 groups.

Glycation Reactions of Casein Micelles.

PubMed

Moeckel, Ulrike; Duerasch, Anja; Weiz, Alexander; Ruck, Michael; Henle, Thomas

2016-04-13

After suspensions of micellar casein or nonmicellar sodium caseinate had been heated, respectively, in the presence and absence of glucose for 0-4 h at 100 °C, glycation compounds were quantitated. The formation of Amadori products as indicators for the "early" Maillard reaction were in the same range for both micellar and nonmicellar caseins, indicating that reactive amino acid side chains within the micelles are accessible for glucose in a comparable way as in nonmicellar casein. Significant differences, however, were observed concerning the formation of the advanced glycation end products (AGEs), namely, N(ε)-carboxymethyllysine (CML), pyrraline, pentosidine, and glyoxal-lysine dimer (GOLD). CML could be observerd in higher amounts in nonmicellar casein, whereas in the micelles the pyrraline formation was increased. Pentosidine and GOLD were formed in comparable amounts. Furthermore, the extent of protein cross-linking was significantly higher in the glycated casein micelles than in the nonmicellar casein samples. Dynamic light scattering and scanning electron microscopy showed that glycation has no influence on the size of the casein micelles, indicating that cross-linking occurs only in the interior of the micelles, but altered the surface morphology. Studies on glycation and nonenzymatic cross-linking can contribute to the understanding of the structure of casein micelles.

Curcumin-loaded chitosan-cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model.

PubMed

Muddineti, Omkara Swami; Kumari, Preeti; Ray, Eupa; Ghosh, Balaram; Biswas, Swati

2017-06-02

To improve the bioavailability and anticancer potential of curcumin by using a cholesterol-conjugated chitosan micelle. Methods & methods: Cholesterol was conjugated to chitosan (15 kDa) to form self-assembled micelles, which loaded curcumin. Physicochemical characterization and formulation optimization of the drug-loaded micelles (curcumin-loaded chitosan-cholesterol micelles [C-CCM]) were performed. In vitro cellular uptake and viability of C-CCM were investigated in melanoma and breast cancer cell lines. The antitumor efficacy was evaluated in 3D lung cancer spheroid model. The optimized C-CCM had size of approximately 162 nm with loading efficiency of approximately 36%. C-CCM was taken up efficiently by the cells, and it reduced cancer cell viability significantly compared with free curcumin. C-CCM enhanced the antitumor efficacy in spheroids, suggesting that C-CCM could be used as an effective chemotherapy in cancer.

Enhanced effect of folated pluronic F87-PLA/TPGS mixed micelles on targeted delivery of paclitaxel.

PubMed

Xiong, Xiang Yuan; Pan, Xiaoqian; Tao, Long; Cheng, Feng; Li, Zi Ling; Gong, Yan Chun; Li, Yu Ping

2017-10-01

Targeted drug delivery systems have great potential to overcome the side effect and improve the bioavailability of conventional anticancer drugs. In order to further improve the antitumor efficacy of paclitaxel (PTX) loaded in folated Pluronic F87/poly(lactic acid) (FA-F87-PLA) micelles, D-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS or Vitamin E TPGS) were added into FA-F87-PLA to form FA-F87-PLA/TPGS mixed micelles. The LE of PTX-loaded mixed micelles (13.5%) was highest in the mass ratio 5 to 3 of FA-F87-PLA to TPGS. The in vitro cytotoxicity assays indicated that the IC50 values for free PTX injections, PTX-loaded FA-F87-PLA micelles and PTX-loaded FA-F87-PLA/TPGS mixed micelles after 72h of incubation were 1.52, 0.42 and 0.037mg/L, respectively. The quantitative cellular uptake of coumarin 6-loaded FA-F87-PLA/TPGS and FA-F87-PLA micelles showed that the cellular uptake efficiency of mixed micelles was higher for 2 and 4h incubation, respectively. In vivo pharmacokinetic studies found that the AUC of PTX-loaded FA-F87-PLA/TPGS mixed micelles is almost 1.4 times of that of PTX-loaded FA-F87-PLA micelles. The decreased particle size and inhibition of P-glycoprotein effect induced by the addition of TPGS could result in enhancing the cellular uptake and improving the antitumor efficiency of PTX-loaded FA-F87-PLA/TPGS mixed micelles. Copyright © 2017 Elsevier B.V. All rights reserved.

Supercritical fluid reverse micelle separation

DOEpatents

Fulton, John L.; Smith, Richard D.

1993-01-01

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.

Supercritical fluid reverse micelle separation

DOEpatents

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

1993-11-30

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.

Multifunctional polymeric micelles loaded with doxorubicin and poly(dithienyl-diketopyrrolopyrrole) for near-infrared light-controlled chemo-phototherapy of cancer cells.

PubMed

Liu, Hui; Wang, Kai; Yang, Cangjie; Huang, Shuo; Wang, Mingfeng

2017-09-01

Polymeric micelles loaded with multiple therapeutic modalities are important to overcome challenges such as drug resistance and improve the therapeutic efficacy. Here we report a new polymer micellar drug carrier that integrates chemotherapy and photothermal therapy in a single platform. Specifically, a narrow bandgap poly(dithienyl-diketopyrrolopyrrole) (PDPP) polymer was encapsulated together with a model anticancer drug doxorubicin (DOX) in the hydrophobic cores of polymeric micelles formed by Pluronic F127, an amphiphilic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer. The PDPP polymer served as an organic photothermal agent that absorbs near-infrared light (700-1000nm) and transforms into heat efficiently. The dual functional micelles co-loaded with PDPP and DOX in the hydrophobic compartment showed good colloidal stability after being stored at 4°C at least over two months, and remained visibly stable after 808-nm laser irradiation. The loaded DOX had negligible effect on the size and photothermal property of the micelles. The release of DOX from the micelles could be enhanced by the "breathing" effect of shrinking/swelling of the micelles induced by the temperature change, owing to the thermosensitive nature of the F127 polymers. Importantly, the ternary F127/PDPP/DOX micelles under 808-nm laser irradiation showed enhanced cytotoxicity against cancer cells such as HeLa cells, compared to F127 micelles containing single modality of either PDPP or DOX only. Copyright © 2017 Elsevier B.V. All rights reserved.

Pluronic®-bile salt mixed micelles.

PubMed

Patel, Vijay; Ray, Debes; Bahadur, Anita; Ma, Junhe; Aswal, V K; Bahadur, Pratap

2018-06-01

The present study was aimed to examine the interaction of two bile salts viz. sodium cholate (NaC) and sodium deoxycholate (NaDC) with three ethylene polyoxide-polypropylene polyoxide (PEO-PPO-PEO) triblock copolymers with similar PPO but varying PEO micelles with a focus on the effect of pH on mixed micelles. Mixed micelles of moderately hydrophobic Pluronic ® P123 were examined in the presence of two bile salts and compared with those from very hydrophobic L121 and very hydrophilic F127. Both the bile salts increase the cloud point (CP) of copolymer solution and decreased apparent micelle hydrodynamic diameter (D h ). SANS study revealed that P123 forms small spherical micelles showing a decrease in size on progressive addition of bile salts. The negatively charged mixed micelles contained fewer P123 molecules but progressively rich in bile salt. NaDC being more hydrophobic displays more pronounced effect than NaC. Interestingly, NaC shows micellar growth in acidic media which has been attributed to the formation of bile acids by protonation of carboxylate ion and subsequent solubilization. In contrast, NaDC showed phase separation at higher concentration. Nuclear Overhauser effect spectroscopy (NOESY) experiments provided information on interaction and location of bile salts in micelles. Results are discussed in terms of hydrophobicity of bile salts and Pluronics ® and the site of bile salt in polymer micelles. Proposed molecular interactions are useful to understand more about bile salts which play important role in physiological processes. Copyright © 2018 Elsevier B.V. All rights reserved.

Micelles of enzymatically synthesized PEG-poly(amine-co-ester) block copolymers as pH-responsive nanocarriers for docetaxel delivery.

PubMed

Zhang, Xiaofang; Liu, Bo; Yang, Zhe; Zhang, Chao; Li, Hao; Luo, Xingen; Luo, Huiyan; Gao, Di; Jiang, Qing; Liu, Jie; Jiang, Zhaozhong

2014-03-01

A series of PEGylated poly(amine-co-ester) terpolymers were successfully synthesized in one step via lipase-catalyzed copolymerization of ω-pentadecalactone (PDL), diethyl sebacate (DES), and N-methyldiethanolamine (MDEA) comonomers in the presence of poly(ethylene glycol) methyl ether as a chain-terminating agent. The resultant amphiphilic poly(ethylene glycol)-poly(PDL-co-MDEA-co-sebacate) (PEG-PPMS) block copolymers consisted of hydrophilic PEG chain segments and hydrophobic random PPMS chain segments, which self-assembled in aqueous medium to form stable, nanosized micelles at physiological pH of 7.4. Upon decreasing the medium pH from 7.4 to 5.0, the copolymer micelles swell significantly due to protonation of the amino groups in the micelle PPMS cores. Correspondingly, docetaxel (DTX)-encapsulated PEG2K-PPMS copolymer micelles showed gradual sustained drug release at pH of 7.4, but remarkably accelerated DTX release at acidic pH of 5.0. The drug-loaded micelle particles were readily internalized by SK-BR-3 cancer cells and, compared to free DTX drug, DTX-loaded micelles of the copolymers with optimal compositions exhibited enhanced potency against the cells. Biodegradable PEG-PPMS copolymer micelles represent a new type of promising, pH-responsive nanocarriers for anticancer drug delivery, and the drug release rate from the micelles can be systematically controlled by both pH and the copolymer composition. Copyright © 2013 Elsevier B.V. All rights reserved.

Doxorubicin-mediated radiosensitivity in multicellular spheroids from a lung cancer cell line is enhanced by composite micelle encapsulation

PubMed Central

Xu, Wen-Hong; Han, Min; Dong, Qi; Fu, Zhi-Xuan; Diao, Yuan-Yuan; Liu, Hai; Xu, Jing; Jiang, Hong-Liang; Zhang, Su-Zhan; Zheng, Shu; Gao, Jian-Qing; Wei, Qi-Chun

2012-01-01

Background The purpose of this study is to evaluate the efficacy of composite doxorubicinloaded micelles for enhancing doxorubicin radiosensitivity in multicellular spheroids from a non-small cell lung cancer cell line. Methods A novel composite doxorubicin-loaded micelle consisting of polyethylene glycolpolycaprolactone/Pluronic P105 was developed, and carrier-mediated doxorubicin accumulation and release from multicellular spheroids was evaluated. We used confocal laser scanning microscopy and flow cytometry to study the accumulation and efflux of doxorubicin from A549 multicellular spheroids. Doxorubicin radiosensitization and the combined effects of irradiation and doxorubicin on cell migration and proliferation were compared for the different doxorubicin delivery systems. Results Confocal laser scanning microscopy and quantitative flow cytometry studies both verified that, for equivalent doxorubicin concentrations, composite doxorubicin-loaded micelles significantly enhanced cellular doxorubicin accumulation and inhibited doxorubicin release. Colony-forming assays demonstrated that composite doxorubicin-loaded micelles are radiosensitive, as shown by significantly reduced survival of cells treated by radiation + composite micelles compared with those treated with radiation + free doxorubicin or radiation alone. The multicellular spheroid migration area and growth ability verified higher radiosensitivity for the composite micelles loaded with doxorubicin than for free doxorubicin. Conclusion Our composite doxorubicin-loaded micelle was demonstrated to have radiosensitization. Doxorubicin loading in the composite micelles significantly increased its cellular uptake, improved drug retention, and enhanced its antitumor effect relative to free doxorubicin, thereby providing a novel approach for treatment of cancer. PMID:22679376

Patchy micelles based on coassembly of block copolymer chains and block copolymer brushes on silica particles.

PubMed

Zhu, Shuzhe; Li, Zhan-Wei; Zhao, Hanying

2015-04-14

Patchy particles are a type of colloidal particles with one or more well-defined patches on the surfaces. The patchy particles with multiple compositions and functionalities have found wide applications from the fundamental studies to practical uses. In this research patchy micelles with thiol groups in the patches were prepared based on coassembly of free block copolymer chains and block copolymer brushes on silica particles. Thiol-terminated and cyanoisopropyl-capped polystyrene-block-poly(N-isopropylacrylamide) block copolymers (PS-b-PNIPAM-SH and PS-b-PNIPAM-CIP) were synthesized by reversible addition-fragmentation chain transfer polymerization and chemical modifications. Pyridyl disulfide-functionalized silica particles (SiO2-SS-Py) were prepared by four-step surface chemical reactions. PS-b-PNIPAM brushes on silica particles were prepared by thiol-disulfide exchange reaction between PS-b-PNIPAM-SH and SiO2-SS-Py. Surface micelles on silica particles were prepared by coassembly of PS-b-PNIPAM-CIP and block copolymer brushes. Upon cleavage of the surface micelles from silica particles, patchy micelles with thiol groups in the patches were obtained. Dynamic light scattering, transmission electron microscopy, and zeta-potential measurements demonstrate the preparation of patchy micelles. Gold nanoparticles can be anchored onto the patchy micelles through S-Au bonds, and asymmetric hybrid structures are formed. The thiol groups can be oxidized to disulfides, which results in directional assembly of the patchy micelles. The self-assembly behavior of the patchy micelles was studied experimentally and by computer simulation.

The development of phytosterol-lecithin mixed micelles and organogels.

PubMed

Matheson, Andrew B; Dalkas, Georgios; Gromov, Andrei; Euston, Stephen R; Clegg, Paul S

2017-12-13

We demonstrate that by mixing the phytosterol-ester oryzanol with lecithin in an organic solvent, both components may be dispersed at much higher concentrations than they may be individually. Dynamic light scattering and molecular dynamics simulations show that the mechanism for this is the formation of r ∼ 4 nm mixed micelles. Infrared spectroscopy and simulations suggest that these micelles are formed due in part to hydrogen bonding of the phosphate of the lecithin head-group, and the phenol group of the oryzanol. Rheology shows that by mixing these materials at an equimolar ratio, highly viscous suspensions are created. Furthermore, by adding water to these samples, a solid-like gel may be formed which offers mechanical properties close to those desired for a margarine type spread, whilst still solubilizing the oryzanol.

A high yield reverse micelle synthesis of catalysts and catalyst precursors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linehan, J.C.; Matson, D.W.; Darab, J.G.

1995-04-01

Reverse micelles or water-in-oil microemulsions have been prepared using a mixed AOT/SDS surfactant to increase the stability of the microemulsion and thereby allow a high loading of particle-forming precursors in the aqueous cores. The Modified Reverse Micelles (MRM), as these new binary surfactant microemulsions are called, have proven useful for the laboratory-scale synthesis of nanoscale metals, metal oxides, metal sulfides, and mixed metal materials. The system allows control over the phase and size of the precipitated crystallites and is ideal for producing nanocrystalline powders and suspensions.

Thermodynamic and kinetic control of charged, amphiphilic triblock copolymer assembly via interaction with organic counterions in solvent mixtures

NASA Astrophysics Data System (ADS)

Cui, Honggang

2007-12-01

Amphiphilic block copolymers, consisting of at least two types of monomers with different affinity to the dissolving solvent(s), have been recognized as a molecular building unit for their chemical tunability and design flexibility. Amphiphilic block copolymers with a chargeable block have structural features of polyelectrolytes, block copolymers and surfactants. The combination of these different features offers great flexibility for developing novel assembled morphologies at the nanoscale and outstanding ability to control and manipulate those morphologies. The nanostructures, formed from the spontaneous association of amphiphilic block copolymer in selective solvents, show promise for applications in nanotechnology and pharmaceuticals, including drug delivery, tissue engineering and bio-imaging. A basic knowledge of their modes of self-assembly and their correspondence to application-related properties is just now being developed and poses a considerable scientific challenge. The goal of this dissertation is to investigate the associative behavior of charged, amphiphilic block copolymers in solvent mixtures while in the presence of organic counterions. Self-assembly of poly (acrylic acid)- block-poly (methyl acrylate)-block-polystyrene (PAA- b-PMA-b-PS) triblock copolymers produces nanodomains in THF/water solution specifically through the interaction with organic counterions (polyamines). These assembled structures can include classic micelles (spheres, cylinders and vesicles), but, more importantly, include non-classic micelles (disks, toroids, branched micelles and segmented micelles). Each micelle structure is stable and reproducible at different assembly conditions. The assembled micellar structures depend on not only solution components (thermodynamics) but also mixing procedure and consequent self-assembly pathway (kinetics). The key factors that determine the thermodynamic interactions that partially define the assembled structures and the kinetic assembly process include THF/water ratio, PS block length, the type and amount of organic counterions, and the mixing pathway. Their formation mechanism has been investigated from three aspects: (i) the chain structure of organic counterions, including spacer length, chain hydrophobicity between ionizable groups and the number of ionizable groups (amine group); (ii) molecular structure of the triblock copolymer, including block length of polystyrene and chain architecture; (iii) relative variation of the components, such as different ratios of THF to water and the different ratios of amine groups to acid groups. The first example of a novel micelle formed was the toroidal micelle. The toroidal micelle morphology, which is theoretically predicted but rarely observed, has been produced by the self assembly of PAA99- b-PMA73-b-PS66 in combination with 2,2-(ethylenedioxy)diethylamine (EDDA) and mixed THF/H2O solvent. It was found that toroids can be constructed by two mechanisms: elimination of energetically unfavored cylindrical micelle endcaps or perforation of disk-like micelles. Three-fold junctions were formed as intermediate structures to facilitate toroidal formation from cylindrical micelles. In order to construct toroids from cylindrical micelles, three requirements must be met: lower bending modulus (flexibility of cylinders), selfattraction between cylinders, and extra endcapping energy originating from chain packing frustration. Extremely high energy spheres can also fuse into toroids. Disk-like micelles can transform into a toroidal morphology when cylindrical packing geometry was initiated along the rims of disk-like micelles via solvent mixing that eventually perforated the disk center. The toroidal morphology can be kinetically trapped by either ridding the system of organic solvent or chemically crosslinking the PAA corona with EDDA via addition of 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide methiodide (DPEM). The interaction of positively-charged, multivalent organic amines with the negatively-charged PAA corona plays a decisive role in the formation of these micelles. Inter-chain binding from the interaction of the two amine end groups of diamines with acid groups from different PAA corona blocks governs the final assembled structures. Diamines with hydrophilic spacers induced the formation of micelles with larger interfacial curvature as the spacer length increased. Disk-like micelles, cylindrical micelles or spherical micelles were observed with the gradual increase of hydrophilic spacer length. Diamines with variable hydrophobic spacers showed a similar effect when the spacer length was less than six methylene units. Application of longer hydrophobic diamines had a reverse effect on the interfacial curvature. This effect was attributed to the interaction of hydrophobic diamine hydrocarbon linking chains with the PMA-b-PS hydrophobic core. These findings indicate an easy method to tune micelle structure with multivalent organic counterions. (Abstract shortened by UMI.)

Dual pH-sensitive supramolecular micelles from star-shaped PDMAEMA based on β-cyclodextrin for drug release.

PubMed

Zhou, Zaishuai; Guo, Feng; Wang, Nairong; Meng, Meng; Li, Guiying

2018-05-23

Star-shaped poly(2-(dimethylamino)ethyl methacrylate) based on β-cyclodextrin (β-CD-(PDMAEMA) 7 ) was synthesized by means of atomic transfer radical polymerization (ATRP). Dual pH-sensitive supramolecular micelles were formed from β-CD-(PDMAEMA) 7 and benzimidazole modified poly(ε-caprolactone) (BM-PCL) through the host-guest interactions between β-CD and benzimidazole. The supramolecular micelles have regular spherical structure with hydrophobic β-CD/BM-PCL as the core and pH-sensitive PDMAEMA as the shell. The hydrophobic PCL as well as the hydrophobic cavity of β-CD can efficiently encapsulate doxorubicin (DOX) with the drug-loading content and entrapment efficiency up to 40% and 86%. The drug release from micelles accelerated when the pH decreased from 7.0 to 2.0 and the temperature increased from 25 °C to 45 °C. MTT assay showed that drug loaded supramolecular micelles exhibited excellent anti-cancer activity than free DOX. These supramolecular micelles have promising potential applications as intelligent nanocarriers in drug delivery system. Copyright © 2018 Elsevier B.V. All rights reserved.

Polymeric micelles in mucosal drug delivery: Challenges towards clinical translation.

PubMed

Sosnik, Alejandro; Menaker Raskin, Maya

2015-11-01

Polymeric micelles are nanostructures formed by the self-aggregation of copolymeric amphiphiles above the critical micellar concentration. Due to the flexibility to tailor different molecular features, they have been exploited to encapsulate motley poorly-water soluble therapeutic agents. Moreover, the possibility to combine different amphiphiles in one single aggregate and produce mixed micelles that capitalize on the features of the different components substantially expands the therapeutic potential of these nanocarriers. Despite their proven versatility, polymeric micelles remain elusive to the market and only a few products are currently undergoing advanced clinical trials or reached clinical application, all of them for the therapy of different types of cancer and administration by the intravenous route. At the same time, they emerge as a nanotechnology platform with great potential for non-parenteral mucosal administration. However, for this, the interaction of polymeric micelles with mucus needs to be strengthened. The present review describes the different attempts to develop mucoadhesive polymeric micelles and discusses the challenges faced in the near future for a successful bench-to-bedside translation. Copyright © 2015 Elsevier Inc. All rights reserved.

Micelle Delivery of Parthenolide to Acute Myeloid Leukemia Cells

PubMed Central

Baranello, Michael P.; Bauer, Louisa; Jordan, Craig T.; Benoit, Danielle S. W.

2018-01-01

Parthenolide (PTL) has shown great promise as a novel anti-leukemia agent as it selectively eliminates acute myeloid leukemia (AML) blast cells and leukemia stem cells (LSCs) while sparing normal hematopoietic cells. This success has not yet translated to the clinical setting because PTL is rapidly cleared from blood due to its hydrophobicity. To increase the aqueous solubility of PTL, we previously developed micelles formed from predominantly hydrophobic amphiphilic diblock copolymers of poly(styrene-alt-maleic anhydride)-b-poly(styrene) (e.g., PSMA100-b-PS258) that exhibit robust PTL loading (75%efficiency, 11% w/w capacity) and release PTL over 24 h. Here, PTL-loaded PSMA-b-PS micelles were thoroughly characterized in vitro for PTL delivery to MV4-11 AML cells. Additionally, the mechanisms governing micelle-mediated cytotoxicity were examined in comparison to free PTL. PSMA-b-PS micelles were taken up by MV4-11 cells as evidenced by transmission electron microscopy and flow cytometry. Specifically, MV4-11 cells relied on clathrin-mediated endocytosis, rather than caveolae-mediated endocytosis and macropinocytosis. In addition, PTL-loaded PSMA-b-PS micelles exhibited a dose-dependent cytotoxicity towards AML cells and were capable of reducing cell viability by 75% at 10 μM PTL, while unloaded micelles were nontoxic. At 10 μM PTL, the cytotoxicity of PTL-loaded micelles increased gradually over 24 h while free PTL achieved maximal cytotoxicity between 2 and 4 h, demonstrating micelle-mediated delivery of PTL to AML cells and stability of the drug-loaded micelle even in the presence of cells. Both free PTL and PTL-loaded micelles induced NF-κB inhibition at 10 μM PTL doses, demonstrating some mechanistic similarities in cytotoxicity. However, free PTL relied more heavily on exofacial free thiol interactions to induce cytotoxicity than PTL-loaded micelles; free PTL cytotoxicity was reduced by over twofold when cell surface free thiols were depleted, where PTL-loaded micelle doses were unaffected by cell surface thiol modulation. The physical properties, stability, and efficacy of PTL-loaded PSMA-b-PS micelles support further development of a leukemia therapeutic with greater bioavailability and the potential to eliminate LSCs. PMID:29552235

PEG-poly(amino acid) block copolymer micelles for tunable drug release.

PubMed

Ponta, Andrei; Bae, Younsoo

2010-11-01

To achieve tunable pH-dependent drug release in tumor tissues. Poly(ethylene glycol)-poly(aspartic acid) [PEG-p(Asp)] containing 12 kDa PEG and pAsp (5, 15, and 35 repeating units) were prepared. Hydrazide linkers with spacers [glycine (Gly) and 4-aminobenzoate (Abz)] were introduced to PEG-p(Asp), followed by drug conjugation [doxorubicin (DOX)]. The block copolymer-drug conjugates were either reconstituted or dialyzed in aqueous solutions to prepare micelles. Drug release patterns were observed under sink conditions at pH 5.0 and 7.4, 37°C, for 48 h. A collection of six block copolymers with different chain lengths and spacers was synthesized. Drug binding yields were 13-43.6%. The polymer-drug conjugates formed <50 nm polymer micelles irrespective of polymer compositions. Gly-introduced polymer micelles showed marginal change in particle size (40 ± 10 nm), while the size of Abz-micelles increased gradually from 10 to 40 nm as the polymer chain lengths increased. Drug release patterns of both Gly and Abz micelles were pH-dependent and tunable. The spacers appear to play a crucial role in controlling drug release and stability of polymer micelles in combination with block copolymer chain lengths. A drug delivery platform for tunable drug release was successfully developed with polymer micelles possessing spacer-modified hydrazone drug-binding linkers.

Brushed block copolymer micelles with pH-sensitive pendant groups for controlled drug delivery.

PubMed

Lee, Hyun Jin; Bae, Younsoo

2013-08-01

To investigate the effects of small aliphatic pendent groups conjugated through an acid-sensitive linker to the core of brushed block copolymer micelles on particle properties. The brushed block copolymers were synthesized by conjugating five types of 2-alkanone (2-butanone, 2-hexanone, 2-octanone, 2-decanone, and 2-dodecanone) through an acid-labile hydrazone linker to poly(ethylene glycol)-poly(aspartate hydrazide) block copolymers. Only block copolymers with 2-hexanone and 2-octanone (PEG-HEX and PEG-OCT) formed micelles with a clinically relevant size (< 50 nm in diameter), low critical micelle concentration (CMC, < 20 μM), and drug entrapment yields (approximately 5 wt.%). Both micelles degraded in aqueous solutions in a pH-dependent manner, while the degradation was accelerated in an acidic condition (pH 5.0) in comparison to pH 7.4. Despite these similar properties, PEG-OCT micelles controlled the entrapment and pH-dependent release of a hydrophobic drug most efficiently, without altering particle size, shape, and stability. The molecular weight of PEG (12 kDa vs 5 kDa) induced no change in pH-controlled drug release rates of PEG-OCT micelles. Acid-labile small aliphatic pendant groups are useful to control the entrapment and release of a hydrophobic drug physically entrapped in the core of brushed block copolymer micelles.

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

PubMed Central

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

2015-01-01

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

Stopped-flow kinetic studies of sphere-to-rod transitions of sodium alkyl sulfate micelles induced by hydrotropic salt.

PubMed

Zhang, Jingyan; Ge, Zhishen; Jiang, Xiaoze; Hassan, P A; Liu, Shiyong

2007-12-15

The kinetics and mechanism of sphere-to-rod transitions of sodium alkyl sulfate micelles induced by hydrotropic salt, p-toluidine hydrochloride (PTHC), were investigated by stopped-flow with light scattering detection. Spherical sodium dodecyl sulfate (SDS) micelles transform into short ellipsoidal shapes at low salt concentrations ([PTHC]/[SDS], chi(PTHC)=0.3 and 0.4). Upon stopped-flow mixing aqueous solutions of spherical SDS micelles with PTHC, the scattered light intensity gradually increases with time. Single exponential fitting of the dynamic traces leads to characteristic relaxation time, tau(g), for the growth process from spherical to ellipsoidal micelles, and it increases with increasing SDS concentrations. This suggests that ellipsoidal micelles might be produced by successive insertion of unimers into spherical micelles, similar to the case of formation of spherical micelles as suggested by Aniansson-Wall (A-W) theory. At chi(PTHC) > or = 0.5, rod-like micelles with much higher axial ratio form. The scattered light intensity exhibits an initially abrupt increase and then levels off. The dynamic curves can be well fitted with single exponential functions, and the obtained tau(g) decreases with increasing SDS concentration. Thus, the growth from spherical to rod-like micelles might proceed via fusion of spherical micelles, in agreement with mechanism proposed by Ikeda et al. At chi(PTHC)=0.3 and 0.6, the apparent activation energies obtained from temperature dependent kinetic studies for the micellar growth are 40.4 and 3.6 kJ/mol, respectively. The large differences between activation energies for the growth from spherical to ellipsoidal micelles at low chi(PTHC) and the sphere-to-rod transition at high chi(PTHC) further indicate that they should follow different mechanisms. Moreover, the sphere-to-rod transition kinetics of sodium alkyl sulfate with varying hydrophobic chain lengths (n=10, 12, 14, and 16) are also studied. The longer the carbon chain lengths, the slower the sphere-to-rod transition.

Development and characterization of a novel drug nanocarrier for oral delivery, based on self-assembled β-casein micelles.

PubMed

Bachar, Michal; Mandelbaum, Amitai; Portnaya, Irina; Perlstein, Hadas; Even-Chen, Simcha; Barenholz, Yechezkel; Danino, Dganit

2012-06-10

β-casein is an amphiphilic protein that self-organizes into well-defined core-shell micelles. We developed these micelles as efficient nanocarriers for oral drug delivery. Our model drug is celecoxib, an anti-inflammatory hydrophobic drug utilized for treatment of rheumatoid arthritis and osteoarthritis, now also evaluated as a potent anticancer drug. This system is unique as it enables encapsulation loads >100-fold higher than other β-casein/drug formulations, and does not require additives as do other formulations that have high loadings. This is combined with the ability to lyophilize the formulation without a cryoprotectant, long-term physical and chemical stability of the resulting powder, and fully reversible reconstitution of the structures by rehydration. The dry dosage form, in which >95% of the drug is encapsulated, meets the daily dose. Cryo-TEM and DLS prove that drug encapsulation results in micelle swelling, and X-ray diffraction shows that the encapsulated drug is amorphous. Altogether, our novel dosage form is highly advantageous for oral administration. Copyright © 2012 Elsevier B.V. All rights reserved.

Enhancing oral bioavailability of quercetin using novel soluplus polymeric micelles

NASA Astrophysics Data System (ADS)

Dian, Linghui; Yu, Enjiang; Chen, Xiaona; Wen, Xinguo; Zhang, Zhengzan; Qin, Lingzhen; Wang, Qingqing; Li, Ge; Wu, Chuanbin

2014-12-01

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.

A fluorescent molecular sensor for pH windows in traditional and polymeric biocompatible micelles: comicellization of anionic species to shift and reshape the ON window.

PubMed

Cavallaro, Gennara; Giammona, Gaetano; Pasotti, Luca; Pallavicini, Piersandro

2011-09-12

A new approach is presented to obtain fluorescent sensors for pH windows that work in water and under biomimetic conditions. A single molecule that features all-covalently linked components is used, thus making it capable of working as a fluorescent sensor with an OFF/ON/OFF response to pH value. The components are a tertiary amine, a pyridine, and a fluorophore (pyrene). The forms with both protonated bases or both neutral bases quench the pyrene fluorescence, whereas the form with the neutral pyridine and protonated amine groups is fluorescent. The molecular sensor is also equipped with a long alkyl chain to make it highly hydrophobic in all its protonated and unprotonated forms, that is, either when neutral or charged. Accordingly, it can be confined at any pH value either in traditional (i.e., low-molecular-weight) nonionic surfactant micelles or inside polymeric, biocompatible micellar containers. Relevant for future applications in vivo, thanks to its strong hydrophobicity, no leakage of the molecular sensor is observed from the polymeric biocompatible micelles. Due to the proximity of the pyridine and amine functions in the molecular structure and the poor hydration inside the micelles, the observed pK(a) values are low so that the ON window is positioned at very low pH values. However, the window can be shifted to biologically relevant values by comicellization of anionic species. In particular, in the micelles of the nonionic surfactant TritonX-100, a shift of the ON window to pH 4-6 is obtained by addition of the anionic sodium dodecyl sulphate surfactant, whose negative charge promotes the stability of the protonated forms of the pyridine and amine fragments. In the case of the polymeric micelles, we introduce the use of the amphiphilic polystyrene sulfonate anionic polyelectrolyte, the comicellization of which induces a shift and sharpening of the ON window that is centered at pH 4. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymeric micelle for tumor pH and folate-mediated targeting.

PubMed

Lee, Eun Seong; Na, Kun; Bae, You Han

2003-08-28

Novel pH-sensitive polymeric mixed micelles composed of poly(L-histidine) (polyHis; M(w) 5000)/PEG (M(n) 2000) and poly(L-lactic acid) (PLLA) (M(n) 3000)/PEG (M(n) 2000) block copolymers with or without folate conjugation were prepared by diafiltration. The micelles were investigated for pH-dependent drug release, folate receptor-mediated internalization and cytotoxicity using MCF-7 cells in vitro. The polyHis/PEG micelles showed accelerated adriamycin release as the pH decreased from 8.0. When the cumulative release for 24 h was plotted as a function of pH, the gradual transition in release rate appeared in a pH range from 8.0 to 6.8. In order to tailor the triggering pH of the polymeric micelles to the more acidic extracellular pH of tumors, while improving the micelle stability at pH 7.4, the PLLA/PEG block copolymer was blended with polyHis/PEG to form mixed micelles. Blending shifted the triggering pH to a lower value. Depending on the amount of PLLA/PEG, the mixed micelles were destabilized in the pH range of 7.2-6.6 (triggering pH for adriamycin release). When the mixed micelles were conjugated with folic acid, the in vitro results demonstrated that the micelles were more effective in tumor cell kill due to accelerated drug release and folate receptor-mediated tumor uptake. In addition, after internalization polyHis was found to be effective for cytosolic ADR delivery by virtue of fusogenic activity. This approach is expected to be useful for treatment of solid tumors in vivo.

Glycyrrhetinic Acid-Mediated Polymeric Drug Delivery Targeting the Acidic Microenvironment of Hepatocellular Carcinoma.

PubMed

Zhang, Jinming; Zhang, Min; Ji, Juan; Fang, Xiefan; Pan, Xin; Wang, Yitao; Wu, Chuanbin; Chen, Meiwan

2015-10-01

The major hurdle of current drug carrier against hepatocellular carcinoma (HCC) is the lack of specific and selective drug delivery to HCC. In this study, a novel glycyrrhetinic acid (GA) and poly(L-Histidine) (PHIS) mediated polymeric drug delivery system was developed to target HCC that have GA binding receptors and release its encapsulated anticancer drug in the acidic microenvironment of HCC. Firstly, GA and PHIS were conjugated to form poly (ethylene glycol)-poly(lactic-co-glycolic acid) (GA-PEG-PHIS-PLGA, GA-PPP) micelles by grafting reaction between active terminal groups. Secondly, andrographolide (AGP) was encapsulated to GA-PPP to make AGP/GA-PPP using the solvent evaporation method. The pH-responsive property of AGP/GA-PPP micelles was validated by monitoring its stability and drug release behavior in different pH conditions. Furthermore, selective hepatocellular uptake of GA-PPP micelles in vitro, liver specific drug accumulation in vivo, as well as the enhanced antitumor effects of AGP/GA-PPP micelles confirmed the HCC targeting property of our novel drug delivery system. Average size of AGP/GA-PPP micelles increased significantly and the encapsulated AGP released faster in vitro at pH 5.0, while micelles keeping stable in pH 7.4. AGP/GA-PPP micelles were uptaken more efficiently by human Hep3B liver cells than that by human MDA-MB-231 breast cancer cells. GA-PPP micelles accumulated specifically in the liver and possessed long retention time in vivo. AGP/GA-PPP micelles significantly inhibited tumor growth and provided better therapeutic outcomes compared to free AGP and AGP/PEG-PLGA(AGP/PP) micelles without GA and PHIS decoration. This novel GA-PPP polymeric carrier is promising for targeted treatment of HCC.

The role of charge in the surfactant-assisted stabilization of the natural product curcumin.

PubMed

Wang, Zifan; Leung, Mandy H M; Kee, Tak W; English, Douglas S

2010-04-20

Colloidal solutions of surfactants that form micelles or vesicles are useful for solubilizing and stabilizing hydrophobic molecules that are otherwise sparingly soluble in aqueous solutions. In this paper we investigate the use of micelles and vesicles prepared from ionic surfactants for solubilizing and stabilizing curcumin, a medicinal natural product that undergoes alkaline hydrolysis in water. We identify spectroscopic signatures to evaluate curcumin partitioning and deprotonation in surfactant mixtures containing micelles or vesicles. These spectroscopic signatures allow us to monitor the interaction of curcumin with charged surfactants over a wide range of pH values. Titration data are presented to show the pH dependence of curcumin interactions with negatively and positively charged micelles and vesicles. In solutions of cationic micelles or positively charged vesicles, strong interaction between the Cur(-1) phenoxide ion and the positively charged surfactants results in a change in the acidity of the phenolic hydrogen and a lowering of the apparent lowest pK(a) value for curcumin. In the microenvironments formed by anionic micelles or negatively charged bilayers, our data indicates that curcumin partitions as the Cur(0) species, which is stabilized by interactions with the respective surfactant aggregates, and this leads to an increase in the apparent pK(a) values. Our results may explain some of the discrepancies within the literature with respect to reported pK(a) values and the acidity of the enolic versus phenolic protons. Hydrolysis rates, quantum yields, and molar absorption coefficients are reported for curcumin in a variety of solutions.

Uniformly sized gold nanoparticles derived from PS-b-P2VP block copolymer templates for the controllable synthesis of Si nanowires.

PubMed

Lu, Jennifer Q; Yi, Sung Soo

2006-04-25

A monolayer of gold-containing surface micelles has been produced by spin-coating solution micelles formed by the self-assembly of the gold-modified polystyrene-b-poly(2-vinylpyridine) block copolymer in toluene. After oxygen plasma removed the block copolymer template, highly ordered and uniformly sized nanoparticles have been generated. Unlike other published methods that require reduction treatments to form gold nanoparticles in the zero-valent state, these as-synthesized nanoparticles are in form of metallic gold. These gold nanoparticles have been demonstrated to be an excellent catalyst system for growing small-diameter silicon nanowires. The uniformly sized gold nanoparticles have promoted the controllable synthesis of silicon nanowires with a narrow diameter distribution. Because of the ability to form a monolayer of surface micelles with a high degree of order, evenly distributed gold nanoparticles have been produced on a surface. As a result, uniformly distributed, high-density silicon nanowires have been generated. The process described herein is fully compatible with existing semiconductor processing techniques and can be readily integrated into device fabrication.

A Mixed Micelle Formulation for Oral Delivery of Vitamin K.

PubMed

Sun, Feilong; Jaspers, Tessa C C; van Hasselt, Peter M; Hennink, Wim E; van Nostrum, Cornelus F

2016-09-01

To develop a stable micellar formulation of vitamin K for oral delivery, because the commercial and clinically used formulation of vitamin K (Konakion® MM) destabilizes at gastric pH resulting in low bioavailability of this vitamin in neonates with cholestasis. Mixed micelles composed of EPC, DSPE-PEG 2000 and glycocholic acid, with and without vitamin K, were prepared by a film hydration method. The influence of pH on the stability of the micelles was analyzed by dynamic light scattering (DLS). The critical micelle concentration (CMC) was determined by fluorescence spectroscopy using pyrene and the morphology was evaluated by transmission electron microscopy . Caco-2 cells were used to study the cytocompatibilty. Mixed micelles with mean diameters from 7.1 to 11.0 nm and a narrow size distribution (PDI < 0.2) were obtained after 3 membrane extrusion cycles. Konakion® MM formed aggregated particles at gastric pH, which was avoided through steric stabilization by introducing PEG. TEM showed that mixed micelles had a spherical size (diameter of around 10 nm) with a narrow size distribution in agreement with the DLS results. The loading capacities for vitamin K of mixed micelles with varying molar fractions of DSPE-PEG and EPC (from 0/100 to 50/50 (mol/mol)) were 10.8-5.0 w%, respectively. The mixed micelles showed good cytocompatibility at concentrations of glycocholic acid between 0.12 and 1.20 mM. Mixed micelles with superior stability to Konakion® MM at low pH were obtained by introducing DSPE-PEG 2000. These are therefore attractive oral formulations for vitamin K.

Amphiphilic graft polymer with reduction breakable main chain prepared via click polymerization and grafting onto

NASA Astrophysics Data System (ADS)

Zhang, Xiaojin; Dai, Yu

2018-06-01

Amphiphilic graft polymer PSS- g-Pal/PEG with reduction breakable main chain was synthesized via click polymerization of dialkynyl (containing disulfide bond) and diazide (containing pendant diol) and one-pot grafting onto of hydrophobic palmitate (Pal) and hydrophilic methoxy poly(ethylene glycol) (PEG). PSS- g-Pal/PEG is able to form polymeric micelles by self-assembly in water via dialysis. Polymeric micelles are nano-sized spheres and the particle size is approximately 70 nm. Of note, polymeric micelles are reduction-responsive owing to the disulfide bonds in main chain of PSS- g-Pal/PEG. Therefore, polymeric micelles prepared from amphiphilic graft polymer PSS- g-Pal/PEG are able to fast release the drugs in the presence of the reducing agents such as DL-dithiothreitol (DTT).

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

2010-12-01

Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

Vertical structures in vibrated wormlike micellar solutions

NASA Astrophysics Data System (ADS)

Epstein, Tamir; Deegan, Robert

2008-11-01

Vertically vibrated shear thickening particulate suspensions can support a free-standing interfaces oriented parallel to gravity. We find that shear thickening worm-like micellar solutions also support such vertical interfaces. Above a threshold in acceleration, the solution spontaneously accumulates into a labyrinthine pattern characterized by a well-defined vertical edge. The formation of vertical structures is of interest because they are unique to shear-thickening fluids, and they indicate the existence of an unknown stress bearing mechanism.

Self-Assembled CNT-Polymer Hybrids in Single-Walled Carbon Nanotubes Dispersed Aqueous Triblock Copolymer Solutions

NASA Astrophysics Data System (ADS)

Vijayaraghavan, D.; Manjunatha, A. S.; Poojitha, C. G.

2018-04-01

We have carried out scanning electron microscopy (SEM), differential scanning calorimetry (DSC), small angle X-ray scattering (SAXS), electrical conductivity, and 1H NMR studies as a function of temperature on single-walled carbon nanotubes (SWCNTs) dispersed aqueous triblock copolymer (P123) solutions. The single-walled carbon nanotubes in this system aggregate to form bundles, and the bundles aggregate to form net-like structures. Depending on the temperature and phases of the polymer, this system exhibits three different self-assembled CNT-polymer hybrids. We find CNT-unimer hybrid at low temperatures, CNT-micelle hybrid at intermediate temperatures wherein the polymer micelles are adsorbed in the pores of the CNT nets, and another type of CNT-micelle hybrid at high temperatures wherein the polymer micelles are adsorbed on the surface of the CNT bundles. Our DSC thermogram showed two peaks related to these structural changes in the CNT-polymer hybrids. Temperature dependence of the 1H NMR chemical shifts of the molecular groups of the polymer and the AC electrical conductivity of the composite also showed discontinuous changes at the temperatures at which the CNT-polymer hybrid's structural changes are seen. Interestingly, for a higher CNT concentration (0.5 wt.%) in the system, the aggregated polymer micelles adsorbed on the CNTs exhibit cone-like and cube-like morphologies at the intermediate and at high temperatures respectively.

Method for the preparation of metal colloids in inverse micelles and product preferred by the method

DOEpatents

Wilcoxon, Jess P.

1992-01-01

A method is provided for preparing catalytic elemental metal colloidal particles (e.g. gold, palladium, silver, rhodium, iridium, nickel, iron, platinum, molybdenum) or colloidal alloy particles (silver/iridium or platinum/gold). A homogeneous inverse micelle solution of a metal salt is first formed in a metal-salt solvent comprised of a surfactant (e.g. a nonionic or cationic surfactant) and an organic solvent. The size and number of inverse micelles is controlled by the proportions of the surfactant and the solvent. Then, the metal salt is reduced (by chemical reduction or by a pulsed or continuous wave UV laser) to colloidal particles of elemental metal. After their formation, the colloidal metal particles can be stabilized by reaction with materials that permanently add surface stabilizing groups to the surface of the colloidal metal particles. The sizes of the colloidal elemental metal particles and their size distribution is determined by the size and number of the inverse micelles. A second salt can be added with further reduction to form the colloidal alloy particles. After the colloidal elemental metal particles are formed, the homogeneous solution distributes to two phases, one phase rich in colloidal elemental metal particles and the other phase rich in surfactant. The colloidal elemental metal particles from one phase can be dried to form a powder useful as a catalyst. Surfactant can be recovered and recycled from the phase rich in surfactant.

DNA-polymer micelles as nanoparticles with recognition ability.

PubMed

Talom, Renée Mayap; Fuks, Gad; Kaps, Leonard; Oberdisse, Julian; Cerclier, Christel; Gaillard, Cédric; Mingotaud, Christophe; Gauffre, Fabienne

2011-11-25

The Watson-Crick binding of DNA single strands is a powerful tool for the assembly of nanostructures. Our objective is to develop polymer nanoparticles equipped with DNA strands for surface-patterning applications, taking advantage of the DNA technology, in particular, recognition and reversibility. A hybrid DNA copolymer is synthesized through the conjugation of a ssDNA (22-mer) with a poly(ethylene oxide)-poly(caprolactone) diblock copolymer (PEO-b-PCl). It is shown that, in water, the PEO-b-PCl-ssDNA(22) polymer forms micelles with a PCl hydrophobic core and a hydrophilic corona made of PEO and DNA. The micelles are thoroughly characterized using electron microscopy (TEM and cryoTEM) and small-angle neutron scattering. The binding of these DNA micelles to a surface through DNA recognition is monitored using a quartz crystal microbalance and imaged by atomic force microscopy. The micelles can be released from the surface by a competitive displacement event. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Temperature tunable micellization of polystyrene-block-poly(2-vinylpyridine) at Si-ionic liquid interface.

PubMed

Lu, Haiyun; Lee, Dong Hyun; Russell, Thomas P

2010-11-16

Highly ordered and stable micelles formed from both symmetric and asymmetric block copolymers of polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) at the Si-ionic liquid (IL) interface have been investigated by scanning force microscopy (SFM) and transmission electron microscopy (TEM). The 1-butyl-3-methylimidazolium trifluoromethanesulfonate IL, a selective and temperature-tunable solvent for the P2VP block, was used and gave rise to block copolymer micelles having different morphologies that strongly depended on the annealing temperature. The effects of film thickness, molecular weight of block copolymers, and experimental conditions, such as preannealing, rinsing, and substrate properties, on the morphologies of block copolymer micelles were also studied. In addition, spherical micelles consisting of PS core and P2VP shell could also be obtained by core-corona inversion by annealing the as-coated micellar film in the IL at high temperatures. The possible mechanism for micelle formation is discussed.

Designing Mixed Detergent Micelles for Uniform Neutron Contrast

DOE PAGES

Oliver, Ryan C.; Pingali, Sai Venkatesh; Urban, Volker S.

2017-09-29

Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural datamore » of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.« less

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

PubMed

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

2015-04-15

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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Designing Mixed Detergent Micelles for Uniform Neutron Contrast

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oliver, Ryan C.; Pingali, Sai Venkatesh; Urban, Volker S.

Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural datamore » of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.« less

Cell membrane-inspired polymeric micelles as carriers for drug delivery.

PubMed

Liu, Gongyan; Luo, Quanqing; Gao, Haiqi; Chen, Yuan; Wei, Xing; Dai, Hong; Zhang, Zongcai; Ji, Jian

2015-03-01

In cancer therapy, surface engineering of drug delivery systems plays an essential role in their colloidal stability, biocompatibility and prolonged blood circulation. Inspired by the cell membrane consisting of phospholipids and glycolipids, a zwitterionic phosphorylcholine functionalized chitosan oligosaccharide (PC-CSO) was first synthesized to mimic the hydrophilic head groups of those amphipathic lipids. Then hydrophobic stearic acid (SA) similar to lipid fatty acids was grafted onto PC-CSO to form amphiphilic PC-CSO-SA copolymers. Cell membrane-mimetic micelles with a zwitterionic surface and a hydrophobic SA core were prepared by the self-assembly of PC-CSO-SA copolymers, showing excellent stability under extreme conditions including protein containing media, high salt content or a wide pH range. Doxorubicin (DOX) was successfully entrapped into polymeric micelles through the hydrophobic interaction between DOX and SA segments. After fast internalization by cancer cells, sustained drug release from micelles to the cytoplasm and nucleus was achieved. This result suggests that these biomimetic polymeric micelles may be promising drug delivery systems in cancer therapy.

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

PubMed

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

2014-05-01

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.

Pressure effect on micellization of non-ionic surfactant Triton X-100

NASA Astrophysics Data System (ADS)

Espinosa, Yanis R.; Caffarena, Ernesto R.; Martínez, Yanina Berrueta; Grigera, J. Raúl

2018-02-01

Micellar aggregates can be arranged in new types of conformational assemblies when they are isotropically compressed. Thus, the pressure effects in the underlying fundamental interactions leading to self-assembly of micellar aggregates can be represented by changes in the phase boundaries with increasing pressure. In this paper, we have employed molecular dynamics simulations to study the self-assembly of micelles composed of the non-ionic surfactant Triton X-100 at the atomic scale, monitoring the changes in the solvation dynamics when the micelles are subjected to a wide range of hydrostatic pressures. The computational molecular model was capable of self-assembling and forming a non-ionic micelle, which subsequently was coupled to a high-pressure barostat producing a geometric transition of the micelle due to changes in the solvation dynamics. Accordingly, under a high pressure regime, the hydrogen bonds are redistributed, the water density is modified, and water acts as an unstructured liquid, capable of penetrating into the micelle.

Novel technique for generating macrophage foam cells for in vitro reverse cholesterol transport studies[S

PubMed Central

Sengupta, Bhaswati; Narasimhulu, Chandrakala Aluganti; Parthasarathy, Sampath

2013-01-01

Generation of foam cells, an essential step for reverse cholesterol transport studies, uses the technique of receptor-dependent macrophage loading with radiolabeled acetylated LDL. In this study, we used the ability of a biologically relevant detergent molecule, lysophosphatidylcholine (lyso-PtdCho), to form mixed micelles with cholesterol or cholesteryl ester (CE) to generate macrophage foam cells. Fluorescent or radiolabeled cholesterol/lyso-PtdCho mixed micelles were prepared and incubated with RAW 264.7 or mouse peritoneal macrophages. Results showed that such micelles were quite stable at 4°C and retained the solubilized cholesterol during one month of storage. Macrophages incubated with cholesterol or CE (unlabeled, fluorescently labeled, or radiolabeled)/lyso-PtdCho mixed micelles accumulated CE as documented by microscopy, lipid staining, labeled oleate incorporation, and by TLC. Such foam cells unloaded cholesterol when incubated with HDL but not with oxidized HDL. We propose that stable cholesterol or CE/lyso-PtdCho micelles would offer advantages over existing methods. PMID:24115226

Gemini-Type Tetraphenylethylene Amphiphiles Containing [12]aneN3 and Long Hydrocarbon Chains as Nonviral Gene Vectors and Gene Delivery Monitors.

PubMed

Ding, Ai-Xiang; Tan, Zheng-Li; Shi, You-Di; Song, Lin; Gong, Bing; Lu, Zhong-Lin

2017-04-05

Four gemini amphiphiles decorated with triazole-[12]aneN 3 as the hydrophilic moiety and various long hydrocarbons as hydrophobic moieties, 1-4, were designed to form micelles possessing the aggregation-induced emission (AIE) property for gene delivery and tracing. All four amphiphiles give ultralow critical micelle concentrations, are pH-/photostable and biocompatible, and completely retard the migration of plasmid DNAs at low concentrations. The DNA-binding abilities of the micelles were fully assessed. The coaggregated nanoparticles of 1-4 with DNAs could convert back into AIE micelles. In vitro transfections indicated that lipids 1 and 2 and their originated liposomes bearing decent delivering abilities have great potentials as nonviral vectors. Finally, on the basis of the transfection and the transitions between condensates and micelles, lipid 2 was singled out as the first example for real-time tracing of the intracellular deliveries of nonlabeled DNA, which provides spatiotemporal messages about the processes of condensate uptake and DNA release.

Core-Shell-Corona Micelles with a Responsive Shell.

PubMed

Gohy, Jean-François; Willet, Nicolas; Varshney, Sunil; Zhang, Jian-Xin; Jérôme, Robert

2001-09-03

A reactor for the synthesis of gold nanoparticles is one of the uses of a poly(styrene)-block-poly(2-vinylpyridine)-block-poly(ethylene oxide) triblock copolymer (PS-b-P2VP-b-PEO) which forms core-shell-corona micelles in water. Very low polydispersity spherical micelles are observed that consist of a PS core surrounded by a pH-sensitive P2VP shell and a corona of PEO chains end-capped by a hydroxyl group. The corona can act as a site for attaching responsive or sensing molecules. © 2001 WILEY-VCH Verlag GmbH, Weinheim, Fed. Rep. of Germany.

Synthesis and characterization of low-toxicity N-caprinoyl-N-trimethyl chitosan as self-assembled micelles carriers for osthole

PubMed Central

Hu, Xiao-juan; Liu, Yang; Zhou, Xiao-feng; Zhu, Qiao-ling; Bei, Yong-yan; You, Ben-gang; Zhang, Chun-ge; Chen, Wei-liang; Wang, Zhou-li; Zhu, Ai-jun; Zhang, Xue-nong; Fan, Yu-jiang

2013-01-01

Novel amphiphilic chitosan derivatives (N-caprinoyl-N-trimethyl chitosan [CA-TMC]) were synthesized by grafting the hydrophobic moiety caprinoyl (CA) and hydrophilic moiety trimethyl chitosan to prepare carriers with good compatibility for poorly soluble drugs. Based on self-assembly, CA-TMC can form micelles with sizes ranging from 136 nm to 212 nm. The critical aggregation concentration increased from 0.6 mg • L−1 to 88 mg • L−1 with decrease in the degree of CA substitution. Osthole (OST) could be easily encapsulated into the CA-TMC micelles. The highest entrapment efficiency and drug loading of OST-loaded CA-TMC micelles(OST/CA-TMC) were 79.1% and 19.1%, respectively. The antitumor efficacy results show that OST/CA-TMC micelles have significant antitumor activity on Hela and MCF-7 cells, with a 50% of cell growth inhibition (IC50) of 35.8 and 46.7 μg. mL−1, respectively. Cell apoptosis was the main effect on cell death of Hela and MCF-7 cells after OST administration. The blank micelles did not affect apoptosis or cell death of Hela and MCF-7 cells. The fluorescence imaging results indicated that OST/CA-TMC micelles could be easily uptaken by Hela and MCF-7 cells and could localize in the cell nuclei. These findings suggest that CA-TMC micelles are promising carriers for OST delivery in cancer therapy. PMID:24106424

Biotoxicity and bioavailability of hydrophobic organic compounds solubilized in nonionic surfactant micelle phase and cloud point system.

PubMed

Pan, Tao; Liu, Chunyan; Zeng, Xinying; Xin, Qiao; Xu, Meiying; Deng, Yangwu; Dong, Wei

2017-06-01

A recent work has shown that hydrophobic organic compounds solubilized in the micelle phase of some nonionic surfactants present substrate toxicity to microorganisms with increasing bioavailability. However, in cloud point systems, biotoxicity is prevented, because the compounds are solubilized into a coacervate phase, thereby leaving a fraction of compounds with cells in a dilute phase. This study extends the understanding of the relationship between substrate toxicity and bioavailability of hydrophobic organic compounds solubilized in nonionic surfactant micelle phase and cloud point system. Biotoxicity experiments were conducted with naphthalene and phenanthrene in the presence of mixed nonionic surfactants Brij30 and TMN-3, which formed a micelle phase or cloud point system at different concentrations. Saccharomyces cerevisiae, unable to degrade these compounds, was used for the biotoxicity experiments. Glucose in the cloud point system was consumed faster than in the nonionic surfactant micelle phase, indicating that the solubilized compounds had increased toxicity to cells in the nonionic surfactant micelle phase. The results were verified by subsequent biodegradation experiments. The compounds were degraded faster by PAH-degrading bacterium in the cloud point system than in the micelle phase. All these results showed that biotoxicity of the hydrophobic organic compounds increases with bioavailability in the surfactant micelle phase but remains at a low level in the cloud point system. These results provide a guideline for the application of cloud point systems as novel media for microbial transformation or biodegradation.

Development of Polysorbate 80/Phospholipid mixed micellar formation for docetaxel and assessment of its in vivo distribution in animal models

NASA Astrophysics Data System (ADS)

Song, Hua; Geng, Hongquan; Ruan, Jing; Wang, Kan; Bao, Chenchen; Wang, Juan; Peng, Xia; Zhang, Xueqing; Cui, Daxiang

2011-04-01

Docetaxel (DTX) is a very important member of taxoid family. Despite several alternative delivery systems reported recently, DTX formulated by Polysorbate 80 and alcohol (Taxotere®) is still the most frequent administration in clinical practice. In this study, we incorporated DTX into Polysorbate 80/Phospholipid mixed micelles and compared its structural characteristics, pharmacokinetics, biodistribution, and blood compatibility with its conventional counterparts. Results showed that the mixed micelles loaded DTX possessed a mean size of approximately 13 nm with narrow size distribution and a rod-like micelle shape. In the pharmacokinetics assessment, there was no significant difference between the two preparations ( P > 0.05), which demonstrated that the DTX in the two preparations may share a similar pharmacokinetic process. However, the Polysorbate 80/Phospholipid mixed micelles can increase the drug residence amount of DTX in kidney, spleen, ovary and uterus, heart, and liver. The blood compatibility assessment study revealed that the mixed micelles were safe for intravenous injection. In conclusion, Polysorbate 80/Phospholipid mixed micelle is safe, can improve the tumor therapeutic effects of DTX in the chosen organs, and may be a potential alternative dosage form for clinical intravenous administration of DTX.

Aggregation-induced emission of 1,8-naphthalimide-casein micelle: investigation by synchronous spectrographic method.

PubMed

Sun, Yang; Liang, Xuhua; Zhao, Yingyong; Fan, Jun

2013-09-01

A novel 1,8-naphthalimide probe 1, bearing two acetic-acid moieties was synthesized. The acetic-acid groups, docked into the sub-domains of casein micelle and bound with tryptophan residues, and the 1,8-naphthalimide chromophore adsorbed on the surface of casein micelle, forming a supermolecule, 1-casein micelle, which exhibited the aggregation-induced synchronous emission (AISE) characters. The effect of pH on the intensity of supermolecule was investigated, and the result indicated that the emission enhancement was mainly due to the 1,8-naphthalimide chromophore aggregated onto the casein micelle. Based on AISE, a novel casein quantification method was developed, which exhibited a good linear range of 0.05-10.0 μg ml(-1) and 0.07-9.5 μg ml(-1) with the detection limits of 2.8 and 3.0 ng ml(-1) . The effects of metal ions and pH on the system of 1-casein micelle were investigated. The proposed method was applied to determine casein in milk samples, and the results were in good agreement with the result of the Biuret method. Copyright © 2013 Verlag Helvetica Chimica Acta AG, Zürich.

Core-shell-corona polymeric micelles as a versatile template for synthesis of inorganic hollow nanospheres.

PubMed

Sasidharan, Manickam; Nakashima, Kenichi

2014-01-21

Hollow, inorganic nanoscale capsules have many applications, from the delivery of encapsulated products for cosmetic and medicinal purposes to use as lightweight composite materials. Early methods for producing inorganic hollow nanospheres using hard templates suffered from low product yield and shell weakness upon template removal. In the past decade, researchers have turned to amphiphilic copolymers to synthesize hollow nanostructures and ordered mesoporous materials. Amphiphilic molecules self-assemble into well-defined nanostructures including spherical micelles. Micelles formed from simple, two-component AB diblock and ABA triblock copolymers, however, have been difficult to work with to construct inorganic hollow nanoparticles, because the corona of the micelle, which serves as the template for the shell, becomes unstable as it absorbs inorganic shell precursors, causing aggregates to form. Newly developed, three-component ABC triblock copolymers may solve this problem. They provide nanoassemblies with more diverse morphological and functional features than AB diblock and ABA triblock copolymers. Micelles formed from ABC triblock copolymers in selective solvents that dissolve only one or two of the blocks provide templates for these improved nanoassemblies. By manipulating individual polymer blocks, one can "encode" additional features at the molecular level. For instance, modifying the functional groups or substitution patterns of the blocks allows better morphological and size control. Insights into polymer self-assembly gained over years of work in our group have set the stage to systematically engineer inorganic spherical hollow nanoparticles using ABC triblock copolymers. In this Account, we report our recent progress in producing diverse, inorganic hollow spherical nanospheres from asymmetric triblock copolymeric micelles with core-shell-corona architecture as templates. We discuss three classes of polymeric micelles-with neutral, cationic, and anionic shell structures-that allow fabrication of a variety of hollow nanoparticles. Importantly, we synthesized all of these particles in water, avoiding use of hazardous organic solvents. We have designed the precursor of the inorganic material to be selectively sorbed into the shell domain, leaving the corona free from the inorganic precursors that would destabilize the micelle. The core, meanwhile, is the template for the formation of the hollow void. By rationally tailoring experimental parameters, we readily and selectively obtained a variety of hollow nanoparticles including silica, hybrid silicas, metal-oxides, metal-carbonates, metal-sulfates, metal-borates, and metal-phosphates. Finally, we highlight the state-of-the-art techniques we used to characterize these nanoparticles, and describe experiments that demonstrate the potential of these hollow particles in drug delivery, and as anode and cathode materials for lithium-ion batteries.

Structural differences between bovine A(1) and A(2) β-casein alter micelle self-assembly and influence molecular chaperone activity.

PubMed

Raynes, J K; Day, L; Augustin, M A; Carver, J A

2015-04-01

Within each milk protein there are many individual protein variants and marked alterations to milk functionality can occur depending on the genetic variants of each protein present. Bovine A(1) and A(2) β-casein (β-CN) are 2 variants that contribute to differences in the gelation performance of milk. The A(1) and A(2) β-CN variants differ by a single AA, the substitution of histidine for proline at position 67. β-Casein not only participates in formation of the casein micelle but also forms an oligomeric micelle itself and functions as a molecular chaperone to prevent the aggregation of a wide range of proteins, including the other caseins. Micelle assembly of A(1) and A(2) β-CN was investigated using dynamic light scattering and small-angle X-ray scattering, whereas protein functionality was assessed using fluorescence techniques and molecular chaperone assays. The A(2) β-CN variant formed smaller micelles than A(1) β-CN, with the monomer-micelle equilibrium of A(2) β-CN being shifted toward the monomer. This shift most likely arose from structural differences between the 2 β-CN variants associated with the adoption of greater polyproline-II helix in A(2) β-CN and most likely led to enhanced chaperone activity of A(2) β-CN compared with A(1) β-CN. The difference in micelle assembly, and hence chaperone activity, may provide explain differences in the functionality of homozygous A(1) and A(2) milk. The results of this study highlight that substitution of even a single AA can significantly alter the properties of an intrinsically unstructured protein such as β-CN and, in this case, may have an effect on the functionality of milk. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Soft-templating synthesis of mesoporous graphitic carbon nitride with enhanced photocatalytic H2 evolution under visible light.

PubMed

Yan, Hongjian

2012-04-07

g-C(3)N(4) with worm-like pore and narrow pore size distribution was synthesized by using Pluronic P123 as soft-template. The worm-like porous g-C(3)N(4) not only possesses high BET surface area but also redshifts its absorbance edge up to 800 nm, and shows photocatalytic activity even when the irradiation light λ > 700 nm. This journal is © The Royal Society of Chemistry 2012

Gelling Mechanism of Aluminum Di-Soaps in Oils

NASA Astrophysics Data System (ADS)

Wang, Xiaorong; Rackaitis, Mindaugas

2009-03-01

This work demonstrates that aluminum di-soaps form nano-sized spherical micelles in the oils and that the aggregation of these micelles forms a network that gives rise to a gel formation -- thereby refuting a long-held belief that the gel formation was the result of linear polymeric chains of aluminum association. The discovery of such aluminum nano-particles could expand application of these materials to new technologies because these materials are chemically inert, odorless and nontoxic, and have been widely used in greases, paints, gels, cosmetics, drugs and foods.

Synthesis and characterization of Fe colloid catalysts in inverse micelle solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martino, A.; Stoker, M.; Hicks, M.

1995-12-31

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 tomore » 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.« less

Gold nanorod embedded reduction responsive block copolymer micelle-triggered drug delivery combined with photothermal ablation for targeted cancer therapy.

PubMed

Parida, Sheetal; Maiti, Chiranjit; Rajesh, Y; Dey, Kaushik K; Pal, Ipsita; Parekh, Aditya; Patra, Rusha; Dhara, Dibakar; Dutta, Pranab Kumar; Mandal, Mahitosh

2017-01-01

Gold nanorods, by virtue of surface plasmon resonance, convert incident light energy (NIR) into heat energy which induces hyperthermia. We designed unique, multifunctional, gold nanorod embedded block copolymer micelle loaded with GW627368X for targeted drug delivery and photothermal therapy. Glutathione responsive diblock co-polymer was synthesized by RAFT process forming self-assembled micelle on gold nanorods prepared by seed mediated method and GW627368X was loaded on to the reduction responsive gold nanorod embedded micelle. Photothermal therapy was administered using cwNIR laser (808nm; 4W/cm 2 ). Efficacy of nanoformulated GW627368X, photothermal therapy and combination of both were evaluated in vitro and in vivo. In response to photothermal treatment, cells undergo regulated, patterned cell death by necroptosis. Combining GW627368X with photothermal treatment using single nanoparticle enhanced therapeutic outcome. In addition, these nanoparticles are effective X-ray CT contrast agents, thus, can help in monitoring treatment. Reduction responsive nanorod embedded micelle containing folic acid and lipoic acid when treated on cervical cancer cells or tumour bearing mice, aggregate in and around cancer cells. Due to high glutathione concentration, micelles degrade releasing drug which binds surface receptors inducing apoptosis. When incident with 808nm cwNIR lasers, gold nanorods bring about photothermal effect leading to hyperthermic cell death by necroptosis. Combination of the two modalities enhances therapeutic efficacy by inducing both forms of cell death. Our proposed treatment strategy achieves photothermal therapy and targeted drug delivery simultaneously. It can prove useful in overcoming general toxicities associated with chemotherapeutics and intrinsic/acquired resistance to chemo and radiotherapy. Copyright © 2016 Elsevier B.V. All rights reserved.

Polymeric microcapsules assembled from a cationic/zwitterionic pair of responsive block copolymer micelles.

PubMed

Addison, Timothy; Cayre, Olivier J; Biggs, Simon; Armes, Steven P; York, David

2010-05-04

Using a layer-by-layer (LbL) approach, this work presents the preparation of hollow microcapsules with a membrane constructed entirely from a cationic/zwitterionic pair of pH-responsive block copolymer micelles. Our previous work with such systems highlighted that, in order to retain the responsive nature of the individual micelles contained within the multilayer membranes, it is important to optimize the conditions required for the selective dissolution of the sacrificial particulate templates. Consequently, here, calcium carbonate particles have been employed as colloidal templates as they can be easily dissolved in aqueous environments with the addition of chelating agents such as ethylenediaminetetraacetic acid (EDTA). Furthermore, the dissolution can be carried out in solutions buffered to a desirable pH so not to adversely affect the pH sensitive micelles forming the capsule membranes. First, we have deposited alternating layers of anionic poly[2-(dimethylamino)ethyl methacrylate-block-poly(2-(diethylamino)ethyl methacrylate)] (PDMA-PDEA) and cationic poly(2-(diethylamino)ethyl)methacrylate-block-poly(methacrylic acid) (PDEA-PMAA) copolymer micelles onto calcium carbonate colloidal templates. After deposition of five micelle bilayers, addition of dilute EDTA solution resulted in dissolution of the calcium carbonate and formation of hollow polymer capsules. The capsules were imaged using atomic force microscopy (AFM) and scanning electron microscopy (SEM), which shows that the micelle/micelle membrane is sufficiently robust to withstand dissolution of the supporting template. Quartz crystal microbalance studies were conducted and provide good evidence that the micelle multilayer structure is retained after EDTA treatment. In addition, a hydrophobic dye was incorporated into the micelle cores prior to adsorption. After dissolution of the particle template, the resulting hollow capsules retained a high concentration of dye, suggesting that the core/shell structure of the micelles remains intact. Finally, thermogravimetric analysis (TGA) of dried capsules confirmed complete removal of the sacrificial inorganic template. As far as we are aware, this is the first demonstration of LbL assembled capsules composed entirely from responsive block copolymer micelles. The results presented here when combined with our previous findings demonstrate that such systems have potential application in the encapsulation and triggered release of actives.

Co-delivery of hydrophilic and hydrophobic drugs by micelles: a new approach using drug conjugated PEG-PCLNanoparticles.

PubMed

Danafar, Hossein; Rostamizadeh, Kobra; Davaran, Soodabeh; Hamidi, Mehrdad

2017-11-01

Co-delivery strategy has been proposed to minimize the amount of each drug and to achieve the synergistic effect for cancer therapies. A conjugate of the antitumor drug, doxorubicin, with diblock methoxy poly (ethylene glycol)-poly caprolactone (mPEG-PCL) copolymer was synthesized by the reaction of mPEG-PCL copolymer with doxorubicin in the presence of p-nitrophenylchloroformate. The conjugated copolymer was characterized in vitro by 1 H-NMR, FTIR, DSC and GPC techniques. Then, the doxorubicin conjugated mPEG-PCL(DOX-mPEG-PCL) was self-assembled into micelles in the presence of curcumin in aqueous solution. The resulting micelles were characterized further by various techniques such as dynamic light scattering (DLS) and atomic force microscopy (AFM).The encapsulation efficiency of doxorubicin and curcumin were 82.31 ± 3.32 and 78.15 ± 3.14%, respectively. The results revealed that the micelles formed by the DOX-mPEG-PCL with and without curcumin have spherical structure with average size of 116 and 134 nm respectively. The release behavior of curcumin and doxorubicin loaded to micelles were investigated in a different media. The release rate of micelles consisted of the conjugated copolymer was pH dependent as it was higher at lower pH than in neutral condition. Another feature of the conjugated micelles was a sustained release profile. The cytotoxicity of micelles were evaluated by MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide, atetrazole) assay on lung cancer A549 cell lines. In vitro cytotoxicity assay showed that the mPEG-PCL copolymer did not affect the growth of A549 cells. The cytotoxic activity of the micelles against A549 cells was greater than free doxorubicin and free curcumin.

pH-responsive unimolecular micelles self-assembled from amphiphilic hyperbranched block copolymer for efficient intracellular release of poorly water-soluble anticancer drugs.

PubMed

Tabatabaei Rezaei, Seyed Jamal; Abandansari, Hamid Sadeghi; Nabid, Mohammad Reza; Niknejad, Hassan

2014-07-01

Novel unimolecular micelles from amphiphilic hyperbranched block copolymer H40-poly(ε-caprolactone)-b-poly(acrylic acid)-b'-methoxy poly(ethylene glycol)/poly(ethylene glycol)-folate (i.e., H40-PCL-b-PAA-b'-MPEG/PEG-FA (HCAE-FA)) as new multifunctional nanocarriers to pH-induced accelerated release and tumor-targeted delivery of poorly water-soluble anticancer drugs were developed. The hydrophobic core of the unimolecular micelle was hyperbranched polyester (H40-poly(ε-caprolactone) (H40-PCL)). The inner hydrophilic layer was composed of PAA segments, while the outer hydrophilic shell was composed of PEG segments. This copolymer formed unimolecular micelles in the aqueous solution with a mean particle size of 33 nm, as determined by dynamic light scattering (DLS) and transmission electron microscopy (TEM). To study the feasibility of micelles as a potential nanocarrier for targeted drug delivery, we encapsulated a hydrophobic anticancer drug, paclitaxel (PTX), in the hydrophobic core, and the loading content was determined by UV-vis analysis to be 10.35 wt.%. In vitro release studies demonstrated that the drug-loaded delivery system is relatively stable at physiologic conditions but susceptible to acidic environments which would trigger the release of encapsulated drugs. Flow cytometry and fluorescent microscope studies revealed that the cellular binding of the FA-conjugated micelles against HeLa cells was higher than that of the neat micelles (without FA). The in vitro cytotoxicity studies showed that the PTX transported by these micelles was higher than that by the commercial PTX formulation Tarvexol®. All of these results show that these unique unimolecular micelles may offer a very promising approach for targeted cancer therapy. Copyright © 2014 Elsevier Inc. All rights reserved.

Nanostructured PEG-based hydrogels with tunable physical properties for gene delivery to human mesenchymal stem cells.

PubMed

Li, Yan; Yang, Chuan; Khan, Majad; Liu, Shaoqiong; Hedrick, James L; Yang, Yi-Yan; Ee, Pui-Lai R

2012-09-01

Effective delivery of DNA to direct cell behavior in a well defined three dimensional scaffold offers a superior approach in tissue engineering. In this study, we synthesized biodegradable nanostructured hydrogels with tunable physical properties for cell and gene delivery. The hydrogels were formed via Michael addition chemistry by reacting a four-arm acrylate-terminated PEG with a four-arm thiol-functionalized PEG. Nanosized micelles self-assembled from the amphiphilic PEG-b-polycarbonate diblock copolymer, having reactive end-groups, were chemically incorporated into the hydrogel networks at various contents. The use of Michael addition chemistry allows for in situ hydrogel formation under the physiological conditions. Mechanical property analysis of the hydrogels revealed a correlation between the content of micelles and the storage modulus of the hydrogels. Internal morphology of hydrogels was observed using a field emission scanning electron microscope, which showed that the number and/or size of the pores in the hydrogel increased with increasing micelle content due to reduced crosslinking degree. There exists an optimal micelle content for cell proliferation and gene transfection. MTT assays demonstrated the highest cell viability in the hydrogel with 20% micelles. The gene expression level in hMSCs in the hydrogel with 20% micelles was also significantly higher than that in the hydrogel without micelles. The enhanced cell viability and gene expression in the hydrogel with the optimized micelle content are likely attributed to the physical properties that provide a better environment for cell-matrix interactions. Therefore, incorporating micelles into the hydrogel is a good strategy to control cellular behavior in 3-D through changes in physical properties of the microenvironment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

PubMed Central

2010-01-01

Biocompatible poly-[N-(2-hydroxyethyl)-d,l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd. PMID:21170410

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel phase formation in dilute triblock copolyelectrolyte complexes

DOE PAGES

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; ...

2017-02-23

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chainmore » aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Finally, our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.« less

Gel Phase Formation in Dilute Triblock Copolyelectrolyte Complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Prabhu, Vivek; de Pablo, Juan; Tirrell, Matthew

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at extremely low polymer concentrations (<1 % by mass) has been observed in scattering experiments and molecular dynamics simulations. In contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing polymer concentrations, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assemblies of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously upon solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of triblock copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries not only contribute to our fundamental understanding of the structure and pathways of complexation driven assemblies, but also raise intriguing prospects for formation of gel structures at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

Gel phase formation in dilute triblock copolyelectrolyte complexes

NASA Astrophysics Data System (ADS)

Srivastava, Samanvaya; Andreev, Marat; Levi, Adam E.; Goldfeld, David J.; Mao, Jun; Heller, William T.; Prabhu, Vivek M.; de Pablo, Juan J.; Tirrell, Matthew V.

2017-02-01

Assembly of oppositely charged triblock copolyelectrolytes into phase-separated gels at low polymer concentrations (<1% by mass) has been observed in scattering experiments and molecular dynamics simulations. Here we show that in contrast to uncharged, amphiphilic block copolymers that form discrete micelles at low concentrations and enter a phase of strongly interacting micelles in a gradual manner with increasing concentration, the formation of a dilute phase of individual micelles is prevented in polyelectrolyte complexation-driven assembly of triblock copolyelectrolytes. Gel phases form and phase separate almost instantaneously on solvation of the copolymers. Furthermore, molecular models of self-assembly demonstrate the presence of oligo-chain aggregates in early stages of copolyelectrolyte assembly, at experimentally unobservable polymer concentrations. Our discoveries contribute to the fundamental understanding of the structure and pathways of complexation-driven assemblies, and raise intriguing prospects for gel formation at extraordinarily low concentrations, with applications in tissue engineering, agriculture, water purification and theranostics.

Simvastatin Prodrug Micelles Target Fracture and Improve Healing

PubMed Central

Dusad, Anand; Yuan, Hongjiang; Ren, Ke; Li, Fei; Fehringer, Edward V.; Purdue, P. Edward; Goldring, Steven R.; Daluiski, Aaron; Wang, Dong

2014-01-01

Simvastatin (SIM), a widely used anti-lipidaemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. In this study, an amphiphilic macromolecular prodrug of SIM was designed and synthesized to overcome these limitations. The polyethylene glycol (PEG)-based prodrug can spontaneously self-assemble to form micelles. The use of SIM trimer as the prodrug’s hydrophobic segment allows easy encapsulation of additional free SIM. The in vitro studies showed that SIM/SIM-mPEG micelles were internalized by MC3T3 cells via lysosomal trafficking and consistently induced expression of both BMP2 and DKK1 mRNA, suggesting that the prodrug micelle retains the biological functions of SIM. After systemic administration, optical imaging suggests that the micelles would passively target to bone fracture sites associated with hematoma and inflammation. Furthermore, flow cytometry study revealed that SIM/SIM-mPEG micelles had preferred cellular uptake by inflammatory and resident cells within the fracture callus tissue. The treatment study using a mouse osteotomy model validated the micelles’ therapeutic efficacy in promoting bone fracture healing as demonstrated by micro-CT and histological analyses. Collectively, these data suggest that the macromolecular prodrug-based micelle formulation of SIM may have great potential for clinical management of impaired fracture healing. PMID:25542644

Neuroendocrine Tumor-Targeted Upconversion Nanoparticle-Based Micelles for Simultaneous NIR-Controlled Combination Chemotherapy and Photodynamic Therapy, and Fluorescence Imaging.

PubMed

Chen, Guojun; Jaskula-Sztul, Renata; Esquibel, Corinne R; Lou, Irene; Zheng, Qifeng; Dammalapati, Ajitha; Harrison, April; Eliceiri, Kevin W; Tang, Weiping; Chen, Herbert; Gong, Shaoqin

2017-02-23

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)-based theranostic micelles are developed for NET-targeted and near-infrared (NIR)-controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light-sensitive amphiphilic block copolymers poly(4,5-dimethoxy-2-nitrobenzyl methacrylate)-polyethylene glycol (PNBMA-PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR-activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR-induced hydrophobic-to-hydrophilic transition of the micelle core and thus enabling NIR-controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate 1 O 2 for NIR-induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET-targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3-loaded UCNP-based micelles conjugated with RB and KE108-enabling NET-targeted combination chemotherapy and PDT-induce the best antitumor efficacy.

Inverse-Micelle-Encapsulated Water-Enabled Bond Breaking of Dialkyl Diselenide/Disulfide: A Critical Step for Synthesizing High- Quality Gold Nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zaluzhna, Oksana; Li, Ying; Allison, Thomas C.

2012-10-09

Inverse-micelle-encapsulated water formed in the two-phase Brust-Schiffrin method (BSM) synthesis of Au nanoparticles (NPs) is identified as essential for dialkyl diselenide/disulfide to react with the Au(III) complex in which the Se-Se/S-S bond is broken, leading to formation of higher-quality Au NPs.

pH-Dependent, Thermosensitive Polymeric Nanocarriers for Drug Delivery to Solid Tumors

PubMed Central

Chen, Ching-Yi; Kim, Tae Hee; Wu, Wen-Chung; Huang, Chi-Ming; Wei, Hua; Mount, Christopher W.; Tian, Yanqing; Jang, Sei-Hum; Pun, Suzie H.; Jen, Alex K-Y

2013-01-01

Polymeric micelles are promising carriers for anticancer agents due to their small size, ease of assembly, and versatility for functionalization. A current challenge in the use of polymeric micelles is the sensitive balance that must be achieved between stability during prolonged blood circulation and release of active drug at the tumor site. Stimuli-responsive materials provide a mechanism for triggered drug release in the acidic tumor and intracellular microenvironments. In this work, we synthesized a series of dual pH- and temperature-responsive block copolymers containing a poly(ε-caprolactone) (PCL) hydrophobic block with a poly(triethylene glycol) block that were copolymerized with an amino acid-functionalized monomer. The block copolymers formed micellar structures in aqueous solutions. An optimized polymer that was functionalized with 6-aminocaproic acid (ACA) possessed pH-sensitive phase transitions at mildly acidic pH and body temperature. Doxorubicin-loaded micelles formed from these polymers were stable at blood pH (~7.4) and showed increased drug release at acidic pH. In addition, these micelles displayed more potent anti-cancer activity than free doxorubicin when tested in a tumor xenograft model in mice. PMID:23498892

Thermo- and pH-Responsive Copolymers Bearing Cholic Acid and Oligo(ethylene glycol) Pendants: Self-Assembly and pH-Controlled Release.

PubMed

Jia, Yong-Guang; Zhu, X X

2015-11-11

A family of block and random copolymers of norbornene derivatives bearing cholic acid and oligo(ethylene glycol) pendants were prepared in the presence of Grubbs' catalyst. The phase transition temperature of the copolymers in aqueous solutions may be tuned by the variation of comonomer ratios and pH values. Both types of copolymers formed micellar nanostructures with a hydrophilic poly(ethylene glycol) shell and a hydrophobic core containing cholic acid residues. The micellar size increased gradually with increasing pH due to the deprotonation of the carboxylic acid groups. These micelles were capable of encapsulating hydrophobic compounds such as Nile Red (NR). A higher hydrophobicity/hydrophilicity ratio in both copolymers resulted in a higher loading capacity for NR. With similar molecular weights and monomer compositions, the block copolymers showed a higher loading capacity for NR than the random copolymers. The NR-loaded micelles exhibited a pH-triggered release behavior. At pH 7.4 within 96 h, the micelles formed by the block and random of copolymers released 56 and 97% NR, respectively. Therefore, these micelles may have promise for use as therapeutic nanocarriers in drug delivery systems.

Detergent-mediated protein aggregation

PubMed Central

Neale, Chris; Ghanei, Hamed; Holyoake, John; Bishop, Russell E.; Privé, Gilbert G.; Pomès, Régis

2016-01-01

Because detergents are commonly used to solvate membrane proteins for structural evaluation, much attention has been devoted to assessing the conformational bias imparted by detergent micelles in comparison to the native environment of the lipid bilayer. Here, we conduct six 500-ns simulations of a system with >600,000 atoms to investigate the spontaneous self assembly of dodecylphosphocholine detergent around multiple molecules of the integral membrane protein PagP. This detergent formed equatorial micelles in which acyl chains surround the protein’s hydrophobic belt, confirming existing models of the detergent solvation of membrane proteins. In addition, unexpectedly, the extracellular and periplasmic apical surfaces of PagP interacted with the headgroups of detergents in other micelles 85 and 60% of the time, respectively, forming complexes that were stable for hundreds of nanoseconds. In some cases, an apical surface of one molecule of PagP interacted with an equatorial micelle surrounding another molecule of PagP. In other cases, the apical surfaces of two molecules of PagP simultaneously bound a neat detergent micelle. In these ways, detergents mediated the non-specific aggregation of folded PagP. These simulation results are consistent with dynamic light scattering experiments, which show that, at detergent concentrations ≥600 mM, PagP induces the formation of large scattering species that are likely to contain many copies of the PagP protein. Together, these simulation and experimental results point to a potentially generic mechanism of detergent-mediated protein aggregation. PMID:23466535

Light Scattering Study of Mixed Micelles Made from Elastin-Like Polypeptide Linear Chains and Trimers

NASA Astrophysics Data System (ADS)

Terrano, Daniel; Tsuper, Ilona; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

Temperature sensitive nanoparticles were generated from a construct (H20F) of three chains of elastin-like polypeptides (ELP) linked to a negatively charged foldon domain. This ELP system was mixed at different ratios with linear chains of ELP (H40L) which lacks the foldon domain. The mixed system is soluble at room temperature and at a transition temperature (Tt) will form swollen micelles with the hydrophobic linear chains hidden inside. This system was studied using depolarized dynamic light scattering (DDLS) and static light scattering (SLS) to determine the size, shape, and internal structure of the mixed micelles. The mixed micelle in equal parts of H20F and H40L show a constant apparent hydrodynamic radius of 40-45 nm at the concentration window from 25:25 to 60:60 uM (1:1 ratio). At a fixed 50 uM concentration of the H20F, varying H40L concentration from 5 to 80 uM resulted in a linear growth in the hydrodynamic radius from about 11 to about 62 nm, along with a 1000-fold increase in VH signal. A possible simple model explaining the growth of the swollen micelles is considered. Lastly, the VH signal can indicate elongation in the geometry of the particle or could possibly be a result from anisotropic properties from the core of the micelle. SLS was used to study the molecular weight, and the radius of gyration of the micelle to help identify the structure and morphology of mixed micelles and the tangible cause of the VH signal.

Design and evaluation of mPEG-PLA micelles functionalized with drug-interactive domains as improved drug carriers for docetaxel delivery.

PubMed

Qi, Dingqing; Gong, Feirong; Teng, Xin; Ma, Mingming; Wen, Huijing; Yuan, Weihao; Cheng, Yi; Lu, Chong

2017-10-01

Polymeric micelles are very attractive drug delivery systems for hydrophobic agents, owing to their readily tailorable chemical structure and ease for scale-up preparation. However, the intrinsic poor stability of drug-loaded micelles presents one of the major challenges for most micellar systems in the translation to clinical applications. In this study, a simple, well-defined, and easy-to-scale up 9-Fluorenylmethoxycarbonyl (Fmoc) and tert-butoxycarbonyl (Boc) containing lysine dendronized mPEG-PLA (mPEG-PLA-Lys(FB) 2 ) micellar formulation was designed and prepared for docetaxel (DTX) delivery, in an effort to improve the stability of the micelles, and its physicochemical properties, pharmacokinetics, and anti-tumor efficacy against SKOV-3 ovarian cancer were evaluated. MPEG-PLA-Lys(FB) 2 was synthesized via a three-step synthetic route, and it actively interacted with DTX in aqueous media to form stable micelles with small particle sizes (~17-19 nm) and narrow size distribution (PI < 0.1), which can be lyophilized and easily reconstituted in saline without significant change in particle size distribution. In vitro drug-release study demonstrated that mPEG-PLA-Lys(FB) 2 micelles achieved delayed and sustained release manner of DTX in comparison with mPEG-PLA micelles. Further in vivo xenograft tumor model in nude mice DTX/mPEG-PLA-Lys(FB) 2 micelles demonstrated significantly higher inhibitory effect on tumor growth than the marketed formulation Taxotere. Thus, our system may hold promise as a simple and effective delivery system for DTX with a potential for translation into clinical study.

Dynamics and motion control of a chain of particles on a rough surface

NASA Astrophysics Data System (ADS)

Behn, C.; Schale, F.; Zeidis, I.; Zimmermann, K.; Bolotnik, N.

2017-05-01

In this paper the mechanics and control of the motion of a straight chain of three particles interconnected with kinematical constraints are investigated. The ground contact is described by dry (discontinuous) or viscous (continuous) friction. Here, we understand this model as a methodological basis for the design of worm-like locomotion systems, i.e., non-pedal mobile robots. This kind of robots will prove an efficient form of locomotion in application to inspection of pipes or for rescue missions. In this paper, a number of issues related to the dynamics and control of artificial limbless locomotion systems are discussed. Simplest models of a limbless locomotor are two-body or three-body systems that move along a horizontal straight line. In the first part of the paper, the controls are assumed in the form of periodic functions with zero average, shifted on a phase one concerning each other. Thus, there is a traveling wave along the chain of particles. In the second part, actuator models are discussed. It is supposed that there are unknown actuator data or the worm system parameter are not known or exactly as well. The focus is on adaptive control algorithms for the worm-like locomotion systems in order to track given reference trajectories, like kinematic gaits. Finally, a prototype together with its signal processing and control software is presented. Theoretically (analytically and numerically) calculated results of the dynamical behavior of the mobile system are compared to experimental data.

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

PubMed

Hassan, P A; Fritz, Gerhard; Kaler, Eric W

2003-01-01

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

Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging.

PubMed

Mouffouk, Fouzi; Simão, Teresa; Dornelles, Daniel F; Lopes, André D; Sau, Pablo; Martins, Jorge; Abu-Salah, Khalid M; Alrokayan, Salman A; Rosa da Costa, Ana M; dos Santos, Nuno R

2015-01-01

Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI.

Block and Gradient Copoly(2-oxazoline) Micelles: Strikingly Different on the Inside.

PubMed

Filippov, Sergey K; Verbraeken, Bart; Konarev, Petr V; Svergun, Dmitri I; Angelov, Borislav; Vishnevetskaya, Natalya S; Papadakis, Christine M; Rogers, Sarah; Radulescu, Aurel; Courtin, Tim; Martins, José C; Starovoytova, Larisa; Hruby, Martin; Stepanek, Petr; Kravchenko, Vitaly S; Potemkin, Igor I; Hoogenboom, Richard

2017-08-17

Herein, we provide a direct proof for differences in the micellar structure of amphiphilic diblock and gradient copolymers, thereby unambiguously demonstrating the influence of monomer distribution along the polymer chains on the micellization behavior. The internal structure of amphiphilic block and gradient co poly(2-oxazolines) based on the hydrophilic poly(2-methyl-2-oxazoline) (PMeOx) and the hydrophobic poly(2-phenyl-2-oxazoline) (PPhOx) was studied in water and water-ethanol mixtures by small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), static and dynamic light scattering (SLS/DLS), and 1 H NMR spectroscopy. Contrast matching SANS experiments revealed that block copolymers form micelles with a uniform density profile of the core. In contrast to popular assumption, the outer part of the core of the gradient copolymer micelles has a distinctly higher density than the middle of the core. We attribute the latter finding to back-folding of chains resulting from hydrophilic-hydrophobic interactions, leading to a new type of micelles that we refer to as micelles with a "bitterball-core" structure.

Sodium effect on self-organization of amphiphilic carboxylates: formation of structured micelles and superlattices.

PubMed

Rosenlehner, Karin; Schade, Boris; Böttcher, Christoph; Jäger, Christof M; Clark, Timothy; Heinemann, Frank W; Hirsch, Andreas

2010-08-16

Not only the self-aggregation of dendritic polycarboxylates into structurally persistent micelles, but also that of the micelles themselves into superlattices is controlled by alkali-metal counterions and shows a pronounced sodium effect. Our combined experimental and computational work has revealed the formation of superlattices for the first time. The behavior of a variety of amphiphilic carboxylates and the different effects of the alkali cations Li(+), Na(+), and K(+) have been investigated by conductivity measurements, cryogenic transmission electron microscopy (cryo-TEM), and molecular-dynamics (MD) simulations. Together, these show that sodium salts of the amphiphiles give the most stable micelles, followed by lithium and potassium. Our results suggest that ion multiplets in bridging positions, rather than contact ion pairs, are responsible for the enhanced stability and the formation of hexagonally ordered superlattices with sodium counterions. Potassium ions do not form such ion multiplets and cannot therefore induce aggregation of the micelles. This sodium effect has far-reaching consequences for a large number of biological and technical systems and sheds new light on the origin of specific-ion effects.

Polymeric micelles based on poly(methacrylic acid) block-containing copolymers with different membrane destabilizing properties for cellular drug delivery.

PubMed

Mebarek, Naila; Aubert-Pouëssel, Anne; Gérardin, Corine; Vicente, Rita; Devoisselle, Jean-Marie; Bégu, Sylvie

2013-10-01

Poly(methacrylic acid)-b-poly(ethylene oxide) are double hydrophilic block copolymers, which are able to form micelles by complexation with a counter-polycation, such as poly-l-lysine. A study was carried out on the ability of the copolymers to interact with model membranes as a function of their molecular weights and as a function of pH. Different behaviors were observed: high molecular weight copolymers respect the membrane integrity, whereas low molecular weight copolymers with a well-chosen asymmetry degree can induce a membrane alteration. Hence by choosing the appropriate molecular weight, micelles with distinct membrane interaction behaviors can be obtained leading to different intracellular traffics with or without endosomal escape, making them interesting tools for cell engineering. Especially micelles constituted of low molecular weight copolymers could exhibit the endosomal escape property, which opens vast therapeutic applications. Moreover micelles possess a homogeneous nanometric size and show variable properties of disassembly at acidic pH, of stability in physiological conditions, and finally of cyto-tolerance. Copyright © 2013 Elsevier B.V. All rights reserved.

New thiol-responsive mono-cleavable block copolymer micelles labeled with single disulfides.

PubMed

Sourkohi, Behnoush Khorsand; Schmidt, Rolf; Oh, Jung Kwon

2011-10-18

Thiol-responsive symmetric triblock copolymers having single disulfide linkages in the middle blocks (called mono-cleavable block copolymers, ss-ABP(2)) were synthesized by atom transfer radical polymerization in the presence of a disulfide-labeled difunctional Br-initiator. These brush-like triblock copolymers consist of a hydrophobic polyacrylate block having pendent oligo(propylene oxide) and a hydrophilic polymethacrylate block having pendent oligo(ethylene oxide). Gel permeation chromatography and (1)H NMR results confirmed the synthesis of well-defined mono-cleavable block copolymers and revealed that polymerizations were well controlled. Because of amphiphilic nature, these copolymers self-assembled to form colloidally stable micelles above critical micellar concentration of 0.032 mg · mL(-1). In response to reductive reactions, disulfides in thiol-responsive micelles were cleaved. Atomic force microscopy and dynamic light scattering analysis suggested that the cleavage of disulfides caused dissociation of micelles to smaller-sized assembled structures in water. Moreover, in a biomedical perspective, the mono-cleavable block copolymer micelles are not cytotoxic and thus biocompatible. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Polymeric Micelles and Alternative Nanonized Delivery Vehicles for Poorly Soluble Drugs

PubMed Central

Lu, Ying; Park, Kinam

2013-01-01

Poorly soluble drugs often encounter low bioavailability and erratic absorption patterns in the clinical setting. Due to the rising number of compounds having solubility issues, finding ways to enhance the solubility of drugs is one of the major challenges in the pharmaceutical industry today. Polymeric micelles, which form upon self-assembly of amphiphilic macromolecules, can act as solubilizing agents for delivery of poorly soluble drugs. This manuscript examines the fundamentals of polymeric micelles through reviews of representative literature and demonstrates possible applications through recent examples of clinical trial developments. In particular, the potential of polymeric micelles for delivery of poorly water-soluble drugs, especially in the areas of oral delivery and in cancer therapy, is discussed. Key considerations in utilizing polymeric micelles’ advantages and overcoming potential disadvantages have been highlighted. Lastly, other possible strategies related to particle size reduction for enhancing solubilization of poorly water-soluble drugs are introduced. PMID:22944304

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

PubMed

Mandal, Abhirup; Bisht, Rohit; Rupenthal, Ilva D; Mitra, Ashim K

2017-02-28

Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Block copolymer micelles as switchable templates for nanofabrication.

PubMed

Krishnamoorthy, Sivashankar; Pugin, Raphaël; Brugger, Juergen; Heinzelmann, Harry; Hoogerwerf, Arno C; Hinderling, Christian

2006-04-11

Block copolymer inverse micelles from polystyrene-block-poly-2-vinylpyridine (PS-b-P2VP) deposited as monolayer films onto surfaces show responsive behavior and are reversibly switchable between two states of different topography and surface chemistry. The as-coated films are in the form of arrays of nanoscale bumps, which can be transformed into arrays of nanoscale holes by switching through exposure to methanol. The use of these micellar films to act as switchable etch masks for the structuring of the underlying material to form either pillars or holes depending on the switching state is demonstrated.

The solubilization of fatty acids in systems based on block copolymers and nonionic surfactants

NASA Astrophysics Data System (ADS)

Mirgorodskaya, A. B.; Yatskevich, E. I.; Zakharova, L. Ya.

2010-12-01

The solubilizing action of micellar, microemulsion, and polymer-colloid systems formed on the basis of biologically compatible amphiphilic polymers and nonionic surfactants on capric, lauric, palmitic, and stearic acids was characterized quantitatively. Systems based on micelle forming oxyethyl compounds increased the solubility of fatty acids by more than an order of magnitude. Acid molecules incorporated into micelles increased their size and caused structural changes. Solubilization was accompanied by complete or partial destruction of intrinsic acid associates and an increase in their p K a by 1.5-2 units compared with water.

Neuroendocrine Tumor-Targeted Upconversion Nanoparticle-Based Micelles for Simultaneous NIR-Controlled Combination Chemotherapy and Photodynamic Therapy, and Fluorescence Imaging

PubMed Central

Chen, Guojun; Jaskula-Sztul, Renata; Esquibel, Corinne R.; Lou, Irene; Zheng, Qifeng; Dammalapati, Ajitha; Harrison, April; Eliceiri, Kevin W.; Tang, Weiping

2017-01-01

Although neuroendocrine tumors (NETs) are slow growing, they are frequently metastatic at the time of discovery and no longer amenable to curative surgery, emphasizing the need for the development of other treatments. In this study, multifunctional upconversion nanoparticle (UCNP)-based theranostic micelles are developed for NET-targeted and near-infrared (NIR)-controlled combination chemotherapy and photodynamic therapy (PDT), and bioimaging. The theranostic micelle is formed by individual UCNP functionalized with light-sensitive amphiphilic block copolymers poly(4,5-dimethoxy-2-nitrobenzyl methacrylate)-polyethylene glycol (PNBMA-PEG) and Rose Bengal (RB) photosensitizers. A hydrophobic anticancer drug, AB3, is loaded into the micelles. The NIR-activated UCNPs emit multiple luminescence bands, including UV, 540 nm, and 650 nm. The UV peaks overlap with the absorption peak of photocleavable hydrophobic PNBMA segments, triggering a rapid drug release due to the NIR-induced hydrophobic-to-hydrophilic transition of the micelle core and thus enabling NIR-controlled chemotherapy. RB molecules are activated via luminescence resonance energy transfer to generate 1O2 for NIR-induced PDT. Meanwhile, the 650 nm emission allows for efficient fluorescence imaging. KE108, a true pansomatostatin nonapeptide, as an NET-targeting ligand, drastically increases the tumoral uptake of the micelles. Intravenously injected AB3-loaded UCNP-based micelles conjugated with RB and KE108—enabling NET-targeted combination chemotherapy and PDT—induce the best antitumor efficacy. PMID:28989337

Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy.

PubMed

Zhao, Shuang; Ma, Litao; Cao, Chengwen; Yu, Qianqian; Chen, Lanmei; Liu, Jie

2017-01-01

At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C 16 -SS-CS-mPEG). These micelles were able to carry and deliver drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)-chitosan-C-C-hexadecyl (C 16 -CC-CS-mPEG) was developed in a similar fashion to that used to yield C 16 -CC-CS-mPEG without a redox-responsive disulfide bond. The cellular uptake mechanisms of both micelles were determined. The efficient intracellular drug release from micelles in MCF-7 cells was further confirmed. Results indicated that curcumin (Cur) could rapidly form C 16 -SS-CS-mPEG@ Cur micelles when exposed to reducing agents and efficaciously enhance intracellular accumulation. The cytotoxicity assay demonstrated that C 16 -SS-CS-mPEG@Cur exhibited satisfactory cytotoxicity against MCF-7 cells. Anti-inflammation assay results indicated that C 16 -SS-CS-mPEG@Cur treatment significantly downregulated tumor necrosis factor (TNF-α) expression and showed good anti-inflammatory effects in tumor microenvironment. Most importantly, antitumor effects in vivo showed satisfactory therapeutic effects with C 16 -SS-CS-mPEG@Cur. Hence, C 16 -SS-CS-mPEG@Cur micelles can be useful in tumor therapy.

Curcumin-loaded redox response of self-assembled micelles for enhanced antitumor and anti-inflammation efficacy

PubMed Central

Zhao, Shuang; Ma, Litao; Cao, Chengwen; Yu, Qianqian; Chen, Lanmei; Liu, Jie

2017-01-01

At present, it has become evident that inflammation plays a critical role in tumor growth; meanwhile, chemotherapeutic agents using nanocarriers have been suggested as a promising strategy in cancer treatment. In this study, novel redox-responsive micelles were prepared from monomethoxy-poly(ethylene glycol)-chitosan-S-S-hexadecyl (C16-SS-CS-mPEG). These micelles were able to carry and deliver drugs into tumor cells. To serve as a control, monomethoxy-poly(ethylene glycol)-chitosan-C-C-hexadecyl (C16-CC-CS-mPEG) was developed in a similar fashion to that used to yield C16-CC-CS-mPEG without a redox-responsive disulfide bond. The cellular uptake mechanisms of both micelles were determined. The efficient intracellular drug release from micelles in MCF-7 cells was further confirmed. Results indicated that curcumin (Cur) could rapidly form C16-SS-CS-mPEG@ Cur micelles when exposed to reducing agents and efficaciously enhance intracellular accumulation. The cytotoxicity assay demonstrated that C16-SS-CS-mPEG@Cur exhibited satisfactory cytotoxicity against MCF-7 cells. Anti-inflammation assay results indicated that C16-SS-CS-mPEG@Cur treatment significantly downregulated tumor necrosis factor (TNF-α) expression and showed good anti-inflammatory effects in tumor microenvironment. Most importantly, antitumor effects in vivo showed satisfactory therapeutic effects with C16-SS-CS-mPEG@Cur. Hence, C16-SS-CS-mPEG@Cur micelles can be useful in tumor therapy. PMID:28408820

Stealth properties of poly(ethylene oxide)-based triblock copolymer micelles: a prerequisite for a pH-triggered targeting system.

PubMed

Van Butsele, K; Morille, M; Passirani, C; Legras, P; Benoit, J P; Varshney, S K; Jérôme, R; Jérôme, C

2011-10-01

Evaluation of the biocompatibility of pH-triggered targeting micelles was performed with the goal of studying the effect of a poly(ethylene oxide) (PEO) coating on micelle stealth properties. Upon protonation under acidic conditions, pH-sensitive poly(2-vinylpyridine) (P2VP) blocks were stretched, exhibiting positive charges at the periphery of the micelles as well as being a model targeting unit. The polymer micelles were based on two different macromolecular architectures, an ABC miktoarm star terpolymer and an ABC linear triblock copolymer, which combined three different polymer blocks, i.e. hydrophobic poly(ε-caprolactone), PEO and P2VP. Neutral polymer micelles were formed at physiological pH. These systems were tested for their ability to avoid macrophage uptake, their complement activation and their pharmacological behavior after systemic injection in mice, as a function of their conformation (neutral or protonated). After protonation, complement activation and macrophage uptake were up to twofold higher than for neutral systems. By contrast, when P2VP blocks and the targeting unit were buried by the PEO shell at physiological pH, micelle stealth properties were improved, allowing their future systemic injection with an expected long circulation in blood. Smart systems responsive to pH were thus developed which therefore hold great promise for targeted drug delivery to an acidic tumoral environment. Copyright © 2011 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The binding of orally dosed hydrophobic active pharmaceutical ingredients to casein micelles in milk.

PubMed

Cheema, M; Hristov, A N; Harte, F M

2017-11-01

Casein proteins (α S1 -, α S2 -, β- and κ-casein) account for 80% of the total protein content in bovine milk and form casein micelles (average diameter = 130 nm, approximately 10 15 micelles/mL). The affinity of native casein micelles with the 3 hydrophobic active pharmaceutical ingredients (API), meloxicam [351.4 g/mol; log P = 3.43; acid dissociation constant (pK a ) = 4.08], flunixin (296.2 g/mol; log P = 4.1; pK a = 5.82), and thiabendazole (201.2 g/mol; log P = 2.92; pK a = 4.64), was evaluated in bovine milk collected from dosed Holstein cows. Native casein micelles were separated from raw bovine milk by mild techniques such as ultracentrifugation, diafiltration, isoelectric point precipitation (pH 4.6), and size exclusion chromatography. Acetonitrile extraction of hydrophobic API was then done, followed by quantification using HPLC-UV. For the API or metabolites meloxicam, 5-hyroxy flunixin and 5-hydroxy thiabendazole, 31 ± 3.90, 31 ± 1.3, and 28 ± 0.5% of the content in milk was associated with casein micelles, respectively. Less than ∼5.0% of the recovered hydrophobic API were found in the milk fat fraction, and the remaining ∼65% were associated with the whey/serum fraction. A separate in vitro study showed that 66 ± 6.4% of meloxicam, 29 ± 0.58% of flunixin, 34 ± 0.21% of the metabolite 5-hyroxy flunixin, 50 ± 4.5% of thiabendazole, and 33 ± 3.8% of metabolite 5-hydroxy thiabendazole was found partitioned into casein micelles. Our study supports the hypothesis that casein micelles are native carriers for hydrophobic compounds in bovine milk. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Determining the morphology of polystyrene-block-poly(2-vinylpyridine) micellar reactors for ZnO nanoparticle synthesis.

PubMed

El-Atwani, Osman; El-Atwani, Osman C; Aytun, Taner; Mutaf, Omer Faruk; Srot, Vesna; van Aken, Peter A; Ow-Yang, Cleva W

2010-05-18

We report the use of reverse PS-b-P2VP diblock copolymer micelles as true nanoscale-sized reactor vessels to synthesize ZnO nanoparticles. The reverse micelles were formed in toluene and then sequentially loaded with zinc acetate dihydrate and tetramethylammonium hydroxide reactants. Moreover, high spatial resolution Z-contrast imaging and EDX spectroscopy techniques were used to confirm the segregation of the Zn cation to the core of the loaded micelles. Determining the chemical distribution with high nanoscale spatial resolution is shown to complement the less direct characterization by AFM, DLS and FTIR, thus demonstrating broader implications for the characterization of hybrid nanocomposite systems.

Molecular Dynamics Simulations of Adsorption of Poly(acrylic acid) and Poly(methacrylic acid) on Dodecyltrimethylammonium Chloride Micelle in Water: Effect of Charge Density.

PubMed

Sulatha, Muralidharan S; Natarajan, Upendra

2015-09-24

We have investigated the interaction of dodecyltrimethylammonium chloride (DoTA) micelle with weak polyelectrolytes, poly(acrylic acid) and poly(methacrylic acid). Anionic as well as un-ionized forms of the polyelectrolytes were studied. Polyelectrolyte-surfactant complexes were formed within 5-11 ns of the simulation time and were found to be stable. Association is driven purely by electrostatic interactions for anionic chains whereas dispersion interactions also play a dominant role in the case of un-ionized chains. Surfactant headgroup nitrogen atoms are in close contact with the carboxylic oxygens of the polyelectrolyte chain at a distance of 0.35 nm. In the complexes, the polyelectrolyte chains are adsorbed on to the hydrophilic micellar surface and do not penetrate into the hydrophobic core of the micelle. Polyacrylate chain shows higher affinity for complex formation with DoTA as compared to polymethacrylate chain. Anionic polyelectrolyte chains show higher interaction strength as compared to corresponding un-ionized chains. Anionic chains act as polymeric counterion in the complexes, resulting in the displacement of counterions (Na(+) and Cl(-)) into the bulk solution. Anionic chains show distinct shrinkage upon adsorption onto the micelle. Detailed information about the microscopic structure and binding characteristics of these complexes is in agreement with available experimental literature.

Cationic surfactants in the form of nanoparticles and micelles elicit different human neutrophil responses: a toxicological study.

PubMed

Hwang, Tsong-Long; Sung, Calvin T; Aljuffali, Ibrahim A; Chang, Yuan-Ting; Fang, Jia-You

2014-02-01

Cationic surfactants are an ingredient commonly incorporated into nanoparticles for clinical practicability; however, the toxicity of cationic surfactants in nanoparticles is not fully elucidated. We aimed to evaluate the inflammatory responses of cationic nanobubbles and micelles in human neutrophils. Soyaethyl morpholinium ethosulfate (SME) and hexadecyltrimethyl-ammonium bromide (CTAB) are the two cationic surfactants employed in this study. The zeta potential of CTAB nanobubbles was 80 mV, which was the highest among all formulations. Nanobubbles, without cationic surfactants, showed no cytotoxic effects on neutrophils in terms of inflammatory responses. Cationic nanobubbles caused a concentration-dependent cytotoxicity of degranulation (elastase release) and membrane damage (release of lactate dehydrogenase, LDH). Among all nanoparticles and micelles, CTAB-containing nanosystems showed the greatest inflammatory responses. A CTAB nanobubble diluent (1/150) increased the LDH release 80-fold. Propidium iodide staining and scanning electron microscopy (SEM) verified cell death and morphological change of neutrophils treated by CTAB nanobubbles. SME, in a micelle form, strengthened the inflammatory response more than SME-loaded nanobubbles. Membrane interaction and subsequent Ca(2+) influx were the mechanisms that triggered inflammation. The information obtained from this work is beneficial in designing nanoparticulate formulations for balancing clinical activity and toxicity. Copyright © 2013 Elsevier B.V. All rights reserved.

Phase behavior and dynamics of a micelle-forming triblock copolymer system

NASA Astrophysics Data System (ADS)

Mohan, P. Harsha; Bandyopadhyay, Ranjini

2008-04-01

Synperonic F-108 (generic name, “pluronic”) is a micelle forming triblock copolymer of type ABA , where A is polyethylene oxide (PEO) and B is polypropylene oxide (PPO). At high temperatures, the hydrophobicity of the PPO chains increase, and the pluronic molecules, when dissolved in an aqueous medium, self-associate into spherical micelles with dense PPO cores and hydrated PEO coronas. At appropriately high concentrations, these micelles arrange in a face centered cubic lattice to show inverse crystallization, with the samples exhibiting high-temperature crystalline and low-temperature fluidlike phases. By studying the evolution of the elastic and viscous moduli as temperature is increased at a fixed rate, we construct the concentration-temperature phase diagram of Synperonic F-108. For a certain range of temperatures and at appropriate sample concentrations, we observe a predominantly elastic response. Oscillatory strain amplitude sweep measurements on these samples show pronounced peaks in the loss moduli, a typical feature of soft solids. The soft solidlike nature of these materials is further demonstrated by measuring their frequency-dependent mechanical moduli. The storage moduli are significantly larger than the loss moduli and are almost independent of the applied angular frequency. Finally, we perform strain rate frequency superposition experiments to measure the slow relaxation dynamics of this soft solid.

Gadolinium-Functionalized Peptide Amphiphile Micelles for Multimodal Imaging of Atherosclerotic Lesions

PubMed Central

2016-01-01

The leading causes of morbidity and mortality globally are cardiovascular diseases, and nanomedicine can provide many improvements including disease-specific targeting, early detection, and local delivery of diagnostic agents. To this end, we designed fibrin-binding, peptide amphiphile micelles (PAMs), achieved by incorporating the targeting peptide cysteine-arginine-glutamic acid-lysine-alanine (CREKA), with two types of amphiphilic molecules containing the gadoliniuim (Gd) chelator diethylenetriaminepentaacetic acid (DTPA), DTPA-bis(stearylamide)(Gd), and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[(poly(ethylene glycol) (PEG))-2000]-DTPA(Gd) (DSPE-PEG2000-DTPA(Gd)). The material characteristics of the resulting nanoparticle diagnostic probes, clot-binding properties in vitro, and contrast enhancement and safety for dual, optical imaging–magnetic resonance imaging (MRI) were evaluated in the atherosclerotic mouse model. Transmission electron micrographs showed a homogenous population of spherical micelles for formulations containing DSPE-PEG2000-DTPA(Gd), whereas both spherical and cylindrical micelles were formed upon mixing DTPA-BSA(Gd) and CREKA amphiphiles. Clot-binding assays confirmed DSPE-PEG2000-DTPA(Gd)-based CREKA micelles targeted clots over 8-fold higher than nontargeting (NT) counterpart micelles, whereas no difference was found between CREKA and NT, DTPA-BSA(Gd) micelles. However, in vivo MRI and optical imaging studies of the aortas and hearts showed fibrin specificity was conferred by the peptide ligand without much difference between the nanoparticle formulations or shapes. Biodistribution studies confirmed that all micelles were cleared through both the reticuloendothelial system and renal clearance, and histology showed no signs of necrosis. In summary, these studies demonstrate the successful synthesis, and the molecular imaging capabilities of two types of CREKA-Gd PAMs for atherosclerosis. Moreover, we demonstrate the differences in micelle formulations and shapes and their outcomes in vitro versus in vivo for site-specific, diagnostic strategies, and provide the groundwork for the detection of thrombosis via contrast-enhancing agents and concurrent therapeutic delivery for theranostic applications. PMID:27917409

The role of aromatic side chain residues in micelle binding by pancreatic colipase. Fluorescence studies of the porcine and equine proteins.

PubMed Central

McIntyre, J C; Hundley, P; Behnke, W D

1987-01-01

Fluorescence techniques have been employed to study the interaction of porcine and equine colipase with pure taurodeoxycholate and mixed micelles. Nitrotyrosine-55 of porcine colipase is obtained by modification with tetranitromethane (low excess, in the presence of taurodeoxycholate) of the protein followed by gel filtration and ion-exchange chromatography. Verification of the residue modified was obtained by h.p.l.c. peptide purification and sequence analysis. Reduction and quantitative reaction with dansyl chloride yields a fluorescent derivative that is twice as active in conjunction with lipase as is native colipase and that exhibits a strong emission band at 550 nm. Addition of micellar concentrations of taurodeoxycholate causes a 4.3-fold increase in the emission maximum as well as a 70 nm blue shift to 480 nm. Inclusion of oleic acid to form a mixed micelle reduces these spectral effects. Scatchard analysis of the data yield a Kd of 6.8 X 10(-4) M and a single colipase-binding site for taurodeoxycholate micelles. The data, by analogy to a phospholipase system, are consistent with a direct insertion of dansyl-NH-tyrosine-55 into the micelle. The presence of a single tryptophan residue (Trp-52) in equine colipase provides an intrinsic fluorescent probe for studying protein-micelle interaction. The emission maximum of horse colipase at 345 nm indicates a solvent-accessible tryptophan residue which becomes less so on binding of micelles. A blue shift of 8 nm and a 2-fold increase in amplitude is indicative of a more hydrophobic environment for tryptophan induced by taurodeoxycholate micelles. There is also a decrease in KSV for acrylamide quenching in the presence of micelles, which further supports a loss of solvent accessibility. The most dramatic pH effects are observed with KI quenching, and may indicate the presence of negative charges near Trp-52. PMID:3663193

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

PubMed

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

2016-03-09

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.

Incessant formation of chain-like mesoporous silica with a superior binding capacity for mercury.

PubMed

Ravi, S; Selvaraj, M

2014-04-14

A novel incessant formation of chain like mesoporous silica (ICMS) has been easily materialized using a mixed surfactant (Pluronic P123 and FC-4) as a structuring reagent in conjunction with a thiol precursor (3-MPS) through a one-pot synthetic method. A particular thiol concentration facilitated the interaction of the micelle head groups to form long-chain micelles, where FC-4 enhanced further growth. The rapid interactions of the micelles and the condensation of silicic acid and its oligomeric derivatives by coordinating 3-MPS through hydrogen bonding interactions leads to form ICMS. The characterization results for the ICMS illustrated that it has an ordered hexagonal pore geometry. The capability of the ICMS for Hg(2+) adsorption was extensively studied under different optimal parameters and the adsorption isothermal values clearly fit with the Langmuir and Freundlich isothermal plots. This novel material exhibited an unprecedentedly high binding affinity toward even microgram levels of mercury ions in wastewater, compared to other thiol-based mesoporous silica.

Novel biocompatible hydrogel nanoparticles: generation and size-tuning of nanoparticles by the formation of micelle templates obtained from thermo-responsive monomers mixtures

NASA Astrophysics Data System (ADS)

Khandadash, Raz; Machtey, Victoria; Shainer, Inbal; Gottlieb, Hugo E.; Gothilf, Yoav; Ebenstein, Yuval; Weiss, Aryeh; Byk, Gerardo

2014-12-01

Biocompatible hydrogel nanoparticles are prepared by polymerization and cross-linking of N-isopropyl acrylamide in a micelle template formed by block copolymers macro-monomers at high temperature. Different monomer ratios form, at high temperature, well-defined micelles of different sizes which are further polymerized leading to nanoparticles with varied sizes from 20 to 390 nm. Physico-chemical characterization of the nanoparticles demonstrates their composition and homogeneity. The NPs were tested in vitro and in vivo biocompatibility assays, and their lack of toxicity was proven. The NPs can be labeled with fluorescent probes, and their intracellular fate can be visualized and quantified using confocal microscopy. Their uptake by live stem cells and distribution in whole developing animals is reported. On the basis of our results, a mechanism of nanoparticle formation is suggested. The lack of toxicity makes these nanoparticles especially attractive for biological applications such as screening and bio-sensing.

3D superstructures with an orthorhombic lattice assembled by colloidal PbS quantum dots.

PubMed

Ushakova, Elena V; Cherevkov, Sergei A; Litvin, Aleksandr P; Parfenov, Peter S; Kasatkin, Igor A; Fedorov, Anatoly V; Gun'ko, Yurii K; Baranov, Alexander V

2018-05-03

We report a new type of metamaterial comprising a highly ordered 3D network of 3-7 nm lead sulfide quantum dots self-assembled in an organic matrix formed by amphiphilic ligands (oleic acid molecules). The obtained 3D superstructures possess an orthorhombic lattice with the distance between the nanocrystals as large as 10-40 nm. Analysis of self-assembly and destruction of the superstructures in time performed by a SAXS technique shows that their morphology depends on the quantity of amphiphilic ligands and width of the quantum dot size and its distribution. Formation of the superstructures is discussed in terms of a model describing the lyotropic crystal formation by micelles from three-phase mixtures. The results show that the organic molecules possessing surfactant properties and capable of forming micelles with nanoparticles as a micelle core can be utilized as building blocks for the creation of novel metamaterials based on a highly ordered 3D network of semiconductors, metals or magnetic nanoparticles.

Design and control of an IPMC wormlike robot.

PubMed

Arena, Paolo; Bonomo, Claudia; Fortuna, Luigi; Frasca, Mattia; Graziani, Salvatore

2006-10-01

This paper presents an innovative wormlike robot controlled by cellular neural networks (CNNs) and made of an ionic polymer-metal composite (IPMC) self-actuated skeleton. The IPMC actuators, from which it is made of, are new materials that behave similarly to biological muscles. The idea that inspired the work is the possibility of using IPMCs to design autonomous moving structures. CNNs have already demonstrated their powerfulness as new structures for bio-inspired locomotion generation and control. The control scheme for the proposed IPMC moving structure is based on CNNs. The wormlike robot is totally made of IPMCs, and each actuator has to carry its own weight. All the actuators are connected together without using any other additional part, thereby constituting the robot structure itself. Worm locomotion is performed by bending the actuators sequentially from "tail" to "head," imitating the traveling wave observed in real-world undulatory locomotion. The activation signals are generated by a CNN. In the authors' opinion, the proposed strategy represents a promising solution in the field of autonomous and light structures that are capable of reconfiguring and moving in line with spatial-temporal dynamics generated by CNNs.

Effect of salt and surfactant concentration on the structure of polyacrylate gel/surfactant complexes.

PubMed

Nilsson, Peter; Unga, Johan; Hansson, Per

2007-09-20

Small-angle X-ray scattering was used to elucidate the structure of crosslinked polyacrylate gel/dodecyltrimethylammonium bromide complexes equilibrated in solutions of varying concentrations of surfactant and sodium bromide (NaBr). Samples were swollen with no ordering (micelle free), or they were collapsed with either several distinct peaks (cubic Pm3n) or one broad correlation peak (disordered micellar). The main factor determining the structure of the collapsed complexes was found to be the NaBr concentration, with the cubic structure existing up to approximately 150 mM NaBr and above which only the disordered micellar structure was found. Increasing the salt concentration decreases the polyion mediated attractive forces holding the micelles together causing swelling of the gel. At sufficiently high salt concentration the micelle-micelle distance in the gel becomes too large for the cubic structure to be retained, and it melts into a disordered micellar structure. As most samples were above the critical micelle concentration, the bulk of the surfactant was in the form of micelles in the solution and the surfactant concentration thereby had only a minor influence on the structure. However, in the region around 150 mM NaBr, increasing the surfactant concentration, at constant NaBr concentration, was found to change the structure from disordered micellar to ordered cubic and back to disordered again.

Shape-designed single-polymer micelles: a proof-of-concept simulation

NASA Astrophysics Data System (ADS)

Moths, Brian; Witten, Thomas A.

Much effort has been directed towards self-assembling nanostructures. Strong, local interactions between specific building blocks often determine these structures (e.g., globular proteins). We seek to produce designed structures that are instead determined by collective effects of weak interactions (e.g., surfactant self-assembly). Such structures may reversibly change conformation or disassemble in response to changing solvent conditions, and, being soft, have potential to adapt to fluctuating or unknown application-imposed shape requirements. Concretely, we aim to realize such a structure in the form of a single polymer micelle--an amphiphilic polymer exhibiting a condensed, phase-segregated conformation when immersed in solvent. Connecting all amphiphiles into a single chain provides geometric constraints controlling the surface curvature profile, thus dictating a non-trivial shape. We present 2D Monte Carlo simulation results demonstrating the feasibility of such soft, shape-designed micelles. Preliminary results demonstrate a stable concave ``dimple'' in a micelle composed of a single A-B multiblock linear copolymer. We discuss both current limitations on shape robustness and effects of block asymmetry, block molecular weights and overall chain length on micelle shape. This work was supported in part by the National Science Foundation's MRSEC Program under Award Number DMR-1420709.

Glutathione responsive micelles incorporated with semiconducting polymer dots and doxorubicin for cancer photothermal-chemotherapy

NASA Astrophysics Data System (ADS)

Cai, Zhixiong; Zhang, Da; Lin, Xinyi; Chen, Yunzhu; Wu, Ming; Wei, Zuwu; Zhang, Zhenxi; Liu, Xiaolong; Yao, Cuiping

2017-10-01

Nanoplatform integrated with photothermal therapy (PTT) and chemotherapy has been recognized a promising agent for enhancing cancer therapeutic outcomes, but still suffer from less controllability for optimizing their synergistic effects. We fabricated glutathione (GSH) responsive micelles incorporated with semiconducting polymer dots and doxorubicin (referred as SPDOX NPs) for combining PTT with chemotherapy to enhance cancer therapeutic efficiency. These micelles, with excellent water dispersibility, comprises of three distinct functional components: (1) the monomethoxy-poly(ethylene glycol)-S-S-hexadecyl (mPEG-S-S-C16), which forms the micelles, can render hydrophobic substances water-soluble and improve the colloidal stability; (2) disulfide linkages can be cleaved in a reductive environment for tumor specific drug release due to the high GSH concentrations of tumor micro-environment; (3) PCPDTBT dots and anti-cancer drug DOX that are loaded inside the hydrophobic core of the micelle can be applied to simultaneously perform PTT and chemotherapy to achieve significantly enhanced tumor killing efficiency both in vitro and in vivo. In summary, our studies demonstrated that our SPDOX NPs with simultaneous photothermal-chemotherapy functions could be a promising platform for a tumor specific responsive drug delivery system.

Investigating Block-Copolymer Micelle Dynamics for Tunable Cargo Delivery

NASA Astrophysics Data System (ADS)

Li, Xiuli; Kidd, Bryce; Cooksey, Tyler; Robertson, Megan; Madsen, Louis

Block-copolymer micelles (BCPMs) can carry molecular cargo in a nanoscopic package that is tunable using polymer structure in combination with cargo properties, as well as with external stimuli such as temperature or pH. For example, BCPMs can be used in targeted anticancer drug delivery due to their biocompatibility, in vivo degradability and prolonged circulation time. We are using NMR spectroscopy and diffusometry as well as SANS to investigate BCPMs. Here we study a diblock poly(ethylene oxide)-b-(caprolactone) (PEO-PCL) that forms spherical micelles at 1% (w/v) in the mixed solvent D2O/THF-d8. We quantify the populations and diffusion coefficients of coexisting micelles and free unimers over a range of temperatures and solvent compositions. We use temperature as a stimulus to enhance unimer exchange and hence trigger cargo release, in some cases at a few degrees above body temperature. We present evidence for dominance of the insertion-expulsion mechanism of unimer exchange in these systems, and we map phase diagrams versus temperature and solvent composition. This study sheds light on how intermolecular interactions fundamentally affect cargo release, unimer exchange, and overall micelle tunability.

Ascorbyl radical disproportionation in reverse micellar systems

NASA Astrophysics Data System (ADS)

Gębicki, J. L.; Szymańska-Owczarek, M.; Pacholczyk-Sienicka, B.; Jankowski, S.

2018-04-01

Ascorbyl radical was generated by the pulse radiolysis method and observed with the fast kinetic spectrophotometry within reverse micelles stabilized by AOT in n-heptane or by Igepal CO-520 in cyclohexane at different water to surfactant molar ratio, w0. Rate constants for the disproportionation of the ascorbyl radicals were smaller than those for intermicellar exchange for both type of reverse micelles and slower than those in homogeneous aqueous solutions. However, they increased with increasing w0 for AOT/n-heptane system, while they decreased for Igepal CO-520 system. The absorption spectra of ascorbic acid AOT/n-heptane reverse micellar system showed that the "pH" sensed by this molecule is lower than that in respective homogeneous aqueous solutions. The obtained results were rationalized taking into account three main factors (i) preferential location of ascorbic acid molecules in the interfacial region of the both types of reverse micelles; (ii) postulate that the pH of the interface is lower than that of the water pool of reverse micelles and (iii) different structure of the interface of the reverse micelles made by AOT in n-heptane and those formed by Igepal CO-520 I cyclohexane. Some possible consequences of these findings are discussed.

Physico-chemical strategies to enhance stability and drug retention of polymeric micelles for tumor-targeted drug delivery

PubMed Central

Shi, Yang; Lammers, Twan; Storm, Gert; Hennink, Wim E.

2017-01-01

Polymeric micelles (PM) have been extensively used for tumor-targeted delivery of hydrophobic anti-cancer drugs. The lipophilic core of PM is naturally suitable for loading hydrophobic drugs and the hydrophilic shell endows them with colloidal stability and stealth properties. Decades of research on PM have resulted in tremendous numbers of PM-forming amphiphilic polymers, and approximately a dozen micellar nanomedicines have entered the clinic. The first generation of PM can be considered solubilizers of hydrophobic drugs, with short circulation times resulting from poor micelle stability and unstable drug entrapment. To more optimally exploit the potential of PM for targeted drug delivery, several physical (e.g. π-π stacking, stereocomplexation, hydrogen bonding, host-guest complexation and coordination interaction) and chemical (e.g. free radical polymerization, click chemistry, disulfide and hydrazone bonding) strategies have been developed to improve micelle stability and drug retention. In this review, we describe the most promising physico-chemical approaches to enhance micelle stability and drug retention, and we summarize how these strategies have resulted in systems with promising therapeutic efficacy in animal models, paving the way for clinical translation. PMID:27413999

Influence of the hydrophilic head size and hydrophobic tail length of surfactants on the ability of micelles to stabilize citral.

PubMed

Hong, Chi Rac; Park, Sung Joon; Choi, Seung Jun

2016-07-01

Surfactant-made micelles can control the rate of chemical degradation of poorly water-soluble food flavors. To evaluate how the molecular structure of surfactant has an influence on the chemical decomposition rate of citral, micelles were prepared with polyoxyethylene alkyl ether-type surfactants that had similar molecular structures but various hydrophilic head sizes and hydrophobic tail lengths. At a critical 20× micelle concentration of surfactant, there was no significant difference in the chemical degradation rate of citral in micelles in neutral pH, regardless of the hydrophilic head size or hydrophobic tail length. In an acidic environment, the degradation rate constant of citral generally increased proportionally with increasing hydrophilic head size of surfactant (0.1563 and 0.2217 for surfactants with 23 and 100 oxyethylene units, respectively) but the length of hydrophobic tail did not affect the citral stability. Also, little difference (0.2217 and 0.2265 for surfactant having 100 oxyethylene units with and without Fe(3+) ) in degradation rate constant of citral between simple micellar solution and micellar solution containing iron suggested that iron ions could not accelerate citral degradation in micelles, regardless of the form of iron (Fe(2+) and Fe(3+) ). This work concludes that although the concentration of surfactant could be relevant, if its concentration could be controlled in the same manner as the critical micelle concentration, then a polyethylene alkyl ether-type surfactant with a small hydrophilic head could more efficiently stabilize citral at an acidic pH. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Fluorescence and electron paramagnetic resonance studies of norfloxacin and N-donor mixed-ligand ternary copper(II) complexes: Stability and interaction with SDS micelles

NASA Astrophysics Data System (ADS)

Vignoli Muniz, Gabriel S.; Incio, Jimmy Llontop; Alves, Odivaldo C.; Krambrock, Klaus; Teixeira, Letícia R.; Louro, Sonia R. W.

2018-01-01

The stability of ternary copper(II) complexes of a heterocyclic ligand, L (L being 2,2‧-bipyridine (bipy) or 1,10-phenanthroline (phen)) and the fluorescent antibacterial agent norfloxacin (NFX) as the second ligand was studied at pH 7.4 and different ionic strengths. Fluorescence quenching upon titration of NFX with the binary complexes allowed to obtain stability constants for NFX binding, Kb, as a function of ionic strength. The Kb values vary by more than two orders of magnitude when buffer concentration varies from 0.5 to 100 mM. It was observed that previously synthesized ternary complexes dissociate in buffer according with the obtained stability constants. This shows that equimolar solutions of NFX and binary complexes are equivalent to solutions of synthesized ternary complexes. The interaction of the ternary copper complexes with anionic SDS (sodium dodecyl sulfate) micelles was studied by fluorescence and electron paramagnetic resonance (EPR). Titration of NFX-loaded SDS micelles with the complexes Cu:L allowed to determine the stability constants inside the micelles. Fluorescence quenching demonstrated that SDS micelles increase the stability constants by factors around 50. EPR spectra gave details of the copper(II) local environment, and demonstrated that the structure of the ternary complexes inside SDS micelles is different from that in buffer. Mononuclear ternary complexes formed inside the micelles, while in buffer most ternary complexes are binuclear. The results show that anionic membrane interfaces increase formation of copper fluoroquinolone complexes, which can influence bioavailability, membrane diffusion, and mechanism of action of the antibiotics.

Conformational statistics of stiff macromolecules as solutions to partial differential equations on the rotation and motion groups

PubMed

Chirikjian; Wang

2000-07-01

Partial differential equations (PDE's) for the probability density function (PDF) of the position and orientation of the distal end of a stiff macromolecule relative to its proximal end are derived and solved. The Kratky-Porod wormlike chain, the Yamakawa helical wormlike chain, and the original and revised Marko-Siggia models are examples of stiffness models to which the present formulation is applied. The solution technique uses harmonic analysis on the rotation and motion groups to convert PDE's governing the PDF's of interest into linear algebraic equations which have mathematically elegant solutions.

Block copolymer micelles with acid-labile ortho ester side-chains: Synthesis, characterization, and enhanced drug delivery to human glioma cells.

PubMed

Tang, Rupei; Ji, Weihang; Panus, David; Palumbo, R Noelle; Wang, Chun

2011-04-10

A new type of block copolymer micelles for pH-triggered delivery of poorly water-soluble anticancer drugs has been synthesized and characterized. The micelles were formed by the self-assembly of an amphiphilic diblock copolymer consisting of a hydrophilic poly(ethylene glycol) (PEG) block and a hydrophobic polymethacrylate block (PEYM) bearing acid-labile ortho ester side-chains. The diblock copolymer was synthesized by atom transfer radical polymerization (ATRP) from a PEG macro-initiator to obtain well-defined polymer chain-length. The PEG-b-PEYM micelles assumed a stable core-shell structure in aqueous buffer at physiological pH with a low critical micelle concentration as determined by proton NMR and pyrene fluorescence spectroscopy. The hydrolysis of the ortho ester side-chain at physiological pH was minimal yet much accelerated at mildly acidic pHs. Doxorubicin (Dox) was successfully loaded into the micelles at pH 7.4 and was released at a much higher rate in response to slight acidification to pH 5. Interestingly, the release of Dox at pH 5 followed apparently a biphasic profile, consisting of an initial fast phase of several hours followed by a sustained release period of several days. Dox loaded in the micelles was rapidly taken up by human glioma (T98G) cells in vitro, accumulating in the endolysosome and subsequently in the nucleus in a few hours, in contrast to the very low uptake of free drug at the same dose. The dose-dependent cytotoxicity of the Dox-loaded micelles was determined by the MTT assay and compared with that of the free Dox. While the empty micelles themselves were not toxic, the IC(50) values of the Dox-loaded micelles were approximately ten-times (by 24h) and three-times (by 48h) lower than the free drug. The much enhanced potency in killing the multi-drug-resistant human glioma cells by Dox loaded in the micelles could be attributed to high intracellular drug concentration and the subsequent pH-triggered drug release. These results establish the PEG-b-PEYM block copolymer with acid-labile ortho ester side-chains as a novel and effective pH-responsive nano-carrier for enhancing the delivery of drugs to cancer cells. Copyright © 2010 Elsevier B.V. All rights reserved.

Self dispersing mixed micelles forming systems for enhanced dissolution and intestinal permeability of hydrochlorothiazide.

PubMed

Sultan, Amal A; El-Gizawy, Sanaa A; Osman, Mohamed A; El Maghraby, Gamal M

2017-01-01

Mixed micelles provide promising strategy for enhancing dissolution and permeability of drugs. However, their fluid nature limited the stability of the loaded drug and hindered the development of stable oral dosage form. Accordingly, the objective was to develop solid self dispersing mixed micelle forming systems (MMFS) for enhanced dissolution and intestinal permeability of hydrochlorothiazide. Pseudoternary phase diagrams were constructed using sodium cholate, lecithin with either poloxamer 407 or PEG 4000 to determine the composition of MMFS. Both polymer free and poloxamer or PEG containing MMFS were prepared as homogenous matrices or as solid self dispersing powder. The later was developed by adsorption of MMFS on avicel-aerosil mixture. Differential scanning calorimetry provided an evidence for existence of hydrochlorothiazide as molecular dispersion in the MMFS. Dispersing polymer free, PEG 4000 or poloxamer based MMFS in aqueous medium produced micelles having size values of 119, 52.6 and 28nm, respectively. The zeta potential values were -61.8, -59.5 and -19.5mV for the same systems, respectively. Preparation of solid self dispersing MMFS enhanced the dissolution rate of hydrochlorothiazide. The intestinal absorption of hydrochlorothiazide from its aqueous solution and polymer incorporating mixed micellar systems was monitored using in situ rabbit intestinal perfusion technique. The permeability results showed a clear trend for enhanced membrane transport of the drug after being incorporated into poloxamer containing mixed micellar system. The study thus introduced a versatile easily formulated solid self dispersing system with high potential for solving the dissolution and permeability problems of class IV drugs. Copyright © 2016 Elsevier B.V. All rights reserved.

Conjugation of curcumin onto alginate enhances aqueous solubility and stability of curcumin.

PubMed

Dey, Soma; Sreenivasan, K

2014-01-01

Curcumin is a potential drug for various diseases including cancer. Prime limitations associated with curcumin are low water solubility, rapid hydrolytic degradation and poor bioavailability. In order to redress these issues we developed Alginate-Curcumin (Alg-Ccm) conjugate which was characterized by FTIR and (1)H NMR spectroscopy. The conjugate self-assembled in aqueous solution forming micelles with an average hydrodynamic diameter of 459 ± 0.32 nm and negative zeta potential. The spherical micelles were visualized by TEM. The critical micelle concentration (CMC) of Alg-Ccm conjugate was determined. A significant enhancement in the aqueous solubility of curcumin was observed upon conjugation with alginate. Formation of micelles improved the stability of curcumin in water at physiological pH. The cytotoxic activity of Alg-Ccm was quantified by MTT assay using L-929 fibroblast cells and it was found to be potentially cytotoxic. Hence, Alg-Ccm could be a promising drug conjugate as well as a nanosized delivery vehicle. Copyright © 2013 Elsevier Ltd. All rights reserved.

Heat-induced gelation of casein micelles in aqueous suspensions at different pH.

PubMed

Thomar, Peggy; Nicolai, Taco

2016-10-01

Heat-induced gelation of casein micelles in aqueous solution was investigated between pH 5.2 and pH 6.7 over a wide range of protein concentrations (C=25-160gL(-1)). For C≥40gL(-1) the casein micelles rapidly formed a self-supporting gel above a critical temperature (Tc). At C=160gL(-1), Tc decreased from 90°C at pH 6.5 to 30°C at pH 5.4 and increased with decreasing protein concentration. Oscillatory shear measurements during heating showed that the elastic modulus (Gel) of the gels increased strongly with increasing protein concentration, but was insensitive to the pH and the heating temperature except close to Tc where Gel decreased sharply with decreasing temperature. The microstructure of the gels was observed by confocal scanning laser microscopy. Heat-induced gelation of casein micelles was compared with that of sodium caseinate solutions free of calcium phosphate. Copyright © 2016 Elsevier B.V. All rights reserved.

Controlled Growth of CdS Quantum Dot in an Amphiphilic Diblock Copolymer Poly(2-Vinyl Pyridine)-b-Poly(n-Hexyl Isocyanate) Reversed Micelle Nanoreactor.

PubMed

Samal, Monica; Mohapatra, Priya Ranjan; Yun, Kyu Sik

2015-09-01

A diblock copolymer poly(2-vinyl pyridine)-b-poly(n-hexyl isocyanate) (P2VP-b-PHIC) is used for the present study. It has two blocks; a rod-shaped PHIC block that adopts a helical conformation, and a coil shaped P2VP block. In a polar solvent such as THF both PHIC and P2VP blocks are soluble. In mixtures of two solvents, such as THF and methanol, while the solubility of P2VP component is augmented that of PHIC is decreased leading to formation of reversed micelles. The pyridine nitrogen in P2VP block is a reactive site. It forms complexes with a suitable metal ion, such as Cd2+. The micelle is employed as a nanoreactor for synthesis of CdS quantum dot (QD). In this paper, the micellization behaviour of the copolymer and the use of the micelles for synthesis and controlled growth of CdS nanocrystals are demonstrated.

Block copolymer micelles with a dual-stimuli-responsive core for fast or slow degradation.

PubMed

Han, Dehui; Tong, Xia; Zhao, Yue

2012-02-07

We report the design and demonstration of a dual-stimuli-responsive block copolymer (BCP) micelle with increased complexity and control. We have synthesized and studied a new amphiphilic ABA-type triblock copolymer whose hydrophobic middle block contains two types of stimuli-sensitive functionalities regularly and repeatedly positioned in the main chain. Using a two-step click chemistry approach, disulfide and o-nitrobenzyle methyl ester groups are inserted into the main chain, which react to reducing agents and light, respectively. With the end blocks being poly(ethylene oxide), micelles formed by this BCP possess a core that can be disintegrated either rapidly via photocleavage of o-nitrobenzyl methyl esters or slowly through cleavage of disulfide groups by a reducing agent in the micellar solution. This feature makes possible either burst release of an encapsulated hydrophobic species from disintegrated micelles by UV light, or slow release by the action of a reducing agent, or release with combined fast-slow rate profiles using the two stimuli.

Solubilization of poorly water-soluble drug carbamezapine in pluronic micelles: effect of molecular characteristics, temperature and added salt on the solubilizing capacity.

PubMed

Kadam, Yogesh; Yerramilli, Usha; Bahadur, Anita

2009-08-01

The solubilization of a poorly water-soluble antiepileptic drug, carbamazepine (CBZ), in a series of micelle-forming PEO-PPO-PEO block copolymers with combinations of blocks having different molecular weight was studied. The drug solubility and micelle-water partition coefficient (P) were determined using UV-vis spectroscopy. Dynamic light scattering on copolymer solutions was used to measure size and polydispersity of nanoaggregates. Solubilization of carbamezapine increased with the rise in temperature and concentration of block copolymers, but no significant increase was observed with added salt (NaCl). The solubilization is also discussed from a thermodynamics viewpoint, by considering the standard free energy of solubilization (DeltaG degrees ).

Click polymerization for the synthesis of reduction-responsive polymeric prodrug

NASA Astrophysics Data System (ADS)

Zhang, Xiaojin; Wang, Hongquan; Dai, Yu

2018-05-01

Click polymerization is a powerful polymerization technique for the construction of new macromolecules with well-defined structures and multifaceted functionalities. Here, we synthesize reduction-responsive polymeric prodrug PEG- b-(PSS- g-MTX)- b-PEG containing disulfide bonds and pendant methotrexate (MTX) via two-step click polymerization followed by conjugating MTX to pendant hydroxyl. MTX content in polymeric prodrug is 13.5%. Polymeric prodrug is able to form polymeric micelles by self-assembly in aqueous solution. Polymeric micelles are spherical nanoparticles with tens of nanometers in size. Of note, polymeric micelles are reduction-responsive due to disulfide bonds in the backbone of PEG- b-(PSS- g-MTX)- b-PEG and could release pendant drugs in the presence of the reducing agents such as dl-dithiothreitol (DTT).

A prodrug micellar carrier assembled from polymers with pendant farnesyl thiosalicylic acid moieties for improved delivery of paclitaxel.

PubMed

Sun, Jingjing; Chen, Yichao; Li, Ke; Huang, Yixian; Fu, Xiaofeng; Zhang, Xiaolan; Zhao, Wenchen; Wei, Yuan; Xu, Liang; Zhang, Peijun; Venkataramanan, Raman; Li, Song

2016-10-01

In order to achieve enhanced and synergistic delivery of paclitaxel (PTX), a hydrophobic anticancer agent, two novel prodrug copolymers, POEG15-b-PFTS6 and POEG15-b-PFTS16 composed of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) and hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) blocks, were synthesized. Both POEG-b-PFTS polymers were able to form micelles with intrinsic antitumor activity in vitro and in vivo. Employing these micelles as a carrier to load PTX, their drug loading capacity, stability, in vivo biodistribution and tumor inhibition effect were evaluated. PTX/POEG15-b-PFTS16 mixed micelles exhibited an excellent stability of 9days at 4°C with a PTX loading capacity of 8.2%, which was more effective than PTX/POEG15-b-PFTS6 mixed micelles. In vivo biodistribution data showed that DiR-loaded POEG-b-PFTS micelles were more effectively localized in the tumor than in other organs. Moreover, both PTX/POEG-b-PFTS micelles showed significantly higher antitumor activity than Taxol in a 4T1.2 murine breast tumor model, and the tumor inhibition and animal survival followed the order of PTX/POEG15-b-PFTS16>PTX/POEG15-b-PFTS6>POEG15-b-PFTS16>Taxol≈POEG15-b-PFTS6. Our data suggest that POEG-b-PFTS micelles are a promising anticancer drug carrier that warrants more studies in the future. Polymerization of drug-based monomer represents a facile and precise method to obtain well-defined polymeric prodrug amphiphiles. Currently, most reports largely focus on the synthesis methods and the biophysical properties. There is limited information about their anti-tumor activity and delivery function as prodrug carriers in vitro and in vivo. In this manuscript, we report the development of two novel prodrug copolymers, POEG15-b-PFTS6 and POEG15-b-PFTS16 composed of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) and hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) blocks. Both POEG-b-PFTS polymers were able to self-assemble into nano-sized micelles with intrinsic antitumor activity in vitro and in vivo. More importantly, POEG-b-PFTS polymers were effective in forming stable mixed micelles with various anticancer agents including PTX, DOX, docetaxel, gefitinib, and imatinib. Delivery of PTX via our new carrier led to significantly improved antitumor activity, suggesting effective PTX/FTS combination therapy. We believe that our study shall be of broad interest to the readers in the fields of biomaterials and drug delivery. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Binding of vitamin A by casein micelles in commercial skim milk

PubMed Central

Mohan, M. S.; Jurat-Fuentes, J. L.; Harte, F.

2015-01-01

Recent studies have shown that reassembled micelles formed by caseinates and purified casein fractions (αs- and β-casein) bind to hydrophobic compounds, including curcumin, docosahexaenoic acid, and vitamin D. However, limited research has been done on the binding of hydrophobic compounds by unmodified casein micelles in skim milk. In the present study, we investigated the ability of casein micelles in commercial skim milk to associate with vitamin A (retinyl palmitate), a fat-soluble vitamin commonly used to fortify milk. Milk protein fractions from different commercially available skim milk samples subjected to different processing treatments, including pasteurized, ultrapasteurized, organic pasteurized, and organic ultrapasteurized milks, were separated by fast protein liquid chromatography. The fractions within each peak were combined and freeze-dried. Sodium dodecyl sulfate-PAGE with silver staining was used to identify the proteins present in each of the fractions. The skim milk samples and fractions were extracted for retinyl palmitate and quantified against a standard using normal phase-HPLC. Retinyl palmitate was found to associate with the fraction of skim milk containing caseins, whereas the other proteins (BSA, β-lactoglobulin, α-lactalbumin) did not show any binding. The retinyl palmitate content in the various samples ranged from 1.59 to 2.48 μg of retinyl palmitate per mL of milk. The casein fractions contained between 14 and 40% of total retinyl palmitate in the various milks tested. The variation in the retention of vitamin A by caseins was probably explained by differences in the processing of different milk samples, including thermal treatment, the form of vitamin A emulsion used for fortification, and the point of fortification during processing. Unmodified casein micelles have a strong intrinsic affinity toward the binding of vitamin A used to fortify commercially available skim milks. PMID:23261375

High drug loading self-microemulsifying/micelle formulation: design by high-throughput formulation screening system and in vivo evaluation.

PubMed

Sakai, Kenichi; Obata, Kouki; Yoshikawa, Mayumi; Takano, Ryusuke; Shibata, Masaki; Maeda, Hiroyuki; Mizutani, Akihiko; Terada, Katsuhide

2012-10-01

To design a high drug loading formulation of self-microemulsifying/micelle system. A poorly-soluble model drug (CH5137291), 8 hydrophilic surfactants (HS), 10 lipophilic surfactants (LS), 5 oils, and PEG400 were used. A high loading formulation was designed by a following stepwise approach using a high-throughput formulation screening (HTFS) system: (1) an oil/solvent was selected by solubility of the drug; (2) a suitable HS for highly loading was selected by the screenings of emulsion/micelle size and phase stability in binary systems (HS, oil/solvent) with increasing loading levels; (3) a LS that formed a broad SMEDDS/micelle area on a phase diagram containing the HS and oil/solvent was selected by the same screenings; (4) an optimized formulation was selected by evaluating the loading capacity of the crystalline drug. Aqueous solubility behavior and oral absorption (Beagle dog) of the optimized formulation were compared with conventional formulations (jet-milled, PEG400). As an optimized formulation, d-α-tocopheryl polyoxyethylene 1000 succinic ester: PEG400 = 8:2 was selected, and achieved the target loading level (200 mg/mL). The formulation formed fine emulsion/micelle (49.1 nm), and generated and maintained a supersaturated state at a higher level compared with the conventional formulations. In the oral absorption test, the area under the plasma concentration-time curve of the optimized formulation was 16.5-fold higher than that of the jet-milled formulation. The high loading formulation designed by the stepwise approach using the HTFS system improved the oral absorption of the poorly-soluble model drug.

Unfolding and refolding details of lysozyme in the presence of β-casein micelles.

PubMed

Wu, Fu-Gen; Luo, Jun-Jie; Yu, Zhi-Wu

2011-02-28

In this work, we selected a small globular protein, lysozyme, to study how it unfolds and refolds in the presence of micelles composed of the unstructured β-casein proteins by using microcalorimetry and circular dichroism spectroscopy. It was found that a partially unfolded structure of lysozyme starts to form when the β-casein/lysozyme molar ratio is above 0.7, and the structure forms exclusively when the β-casein/lysozyme molar ratio is above 1.6. This partially unfolded state of lysozyme loses most of its tertiary structure and after heating, the denatured lysozyme molecules are trapped in the charged coatings of β-casein micelles and cannot refold upon cooling. The thus obtained protein complex can be viewed as a kind of special polyelectrolyte complex micelle. The net charge ratios of the two proteins and the ionic strength of the dispersions can significantly modulate the electrostatic and hydrophobic interactions between the two proteins. Our present work may have implications for the nanoparticle protein engineering therapy in the biomedicine field and may provide a better understanding of the principles governing the protein-protein interactions. Besides, the heating-cooling-reheating procedure employed in this work can also be used to study the unfolding and refolding details of the target protein in other protein-protein, protein-polymer and protein-small solute systems.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ray, D.; Aswal, V. K., E-mail: vkaswal@barc.gov.in; Kohlbrecher, J.

2015-04-28

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 electrolytemore » (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.« less

Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection.

PubMed

Christie, R James; Matsumoto, Yu; Miyata, Kanjiro; Nomoto, Takahiro; Fukushima, Shigeto; Osada, Kensuke; Halnaut, Julien; Pittella, Frederico; Kim, Hyun Jin; Nishiyama, Nobuhiro; Kataoka, Kazunori

2012-06-26

Small interfering ribonucleic acid (siRNA) cancer therapies administered by intravenous injection require a delivery system for transport from the bloodstream into the cytoplasm of diseased cells to perform the function of gene silencing. Here we describe nanosized polymeric micelles that deliver siRNA to solid tumors and elicit a therapeutic effect. Stable multifunctional micelle structures on the order of 45 nm in size formed by spontaneous self-assembly of block copolymers with siRNA. Block copolymers used for micelle formation were designed and synthesized to contain three main features: a siRNA binding segment containing thiols, a hydrophilic nonbinding segment, and a cell-surface binding peptide. Specifically, poly(ethylene glycol)-block-poly(L-lysine) (PEG-b-PLL) comprising lysine amines modified with 2-iminothiolane (2IT) and the cyclo-Arg-Gly-Asp (cRGD) peptide on the PEG terminus was used. Modification of PEG-b-PLL with 2IT led to improved control of micelle formation and also increased stability in the blood compartment, while installation of the cRGD peptide improved biological activity. Incorporation of siRNA into stable micelle structures containing the cRGD peptide resulted in increased gene silencing ability, improved cell uptake, and broader subcellular distribution in vitro and also improved accumulation in both the tumor mass and tumor-associated blood vessels following intravenous injection into mice. Furthermore, stable and targeted micelles inhibited the growth of subcutaneous HeLa tumor models and demonstrated gene silencing in the tumor mass following treatment with antiangiogenic siRNAs. This new micellar nanomedicine could potentially expand the utility of siRNA-based therapies for cancer treatments that require intravenous injection.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lipfert, Jan; Columbus, Linda; Chu, Vincent B.

2009-04-29

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.more » 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.« less

Quenching mechanisms and diffusional pathways in micellar systems unravelled by time-resolved magnetic-field effects.

PubMed

Goez, Martin; Henbest, Kevin B; Windham, Emma G; Maeda, Kiminori; Timmel, Christiane R

2009-06-08

Magnetic-field effects (MFEs) are used to investigate the photoreaction of xanthone (A) and DABCO (D) in anionic (SDS) or cationic (DTAC) micelles at high pH (DABCO = 1,4-diazabicyclo[2.2.2]octane, SDS = sodium dodecyl sulfate, DTAC = dodecyl trimethyl ammonium chloride). From MFE experiments with nanosecond time resolution, the radical anion A(.)(-) can be observed without any interference from the much more strongly absorbing triplet (3)A*, the different quenching processes can be separated and their rates can be measured. Triplet (3)A* is quenched dynamically both by the SDS micelle (k(1) = 5.0x10(5) s(-1)) and by DABCO approaching from the aqueous phase (k(2) = 2.0x10(9) M(-1) s(-1)). Static quenching by solubilised DABCO (association constant with the SDS micelles, 1.5 M(-1)) also participates at high DABCO concentrations, but is chemically nonproductive and does not lead to MFE generation. The MFEs stemming from the radical ion pairs A(.)(-) D(.)(+) are about 40 times larger in the anionic micelles than in the cationic ones despite a higher yield of free radicals in the latter case. This can be rationalised by different diffusional dynamics: Because of the location of their precursors, A(.)(-) and D(.)(+) are formed at opposite sides of the micelle boundary. Subsequently, the negatively charged Stern layer of the SDS micelle traps the radical cation, which then undergoes surface diffusion, so both the recombination probability and the spin mixing are high; in contrast, the positive surface charge of the DTAC micelle forces the radical cation into the bulk of the solution, thus efficiently blocking a recombination.

Supramolecular structure of the casein micelle.

PubMed

McMahon, D J; Oommen, B S

2008-05-01

The supramolecular structure of colloidal casein micelles in milk was investigated by using a sample preparation protocol based on adsorption of proteins onto a poly-l-lysine and parlodion-coated copper grid, staining of proteins and calcium phosphate by uranyl oxalate, instantaneous freezing, and drying under a high vacuum. High-resolution transmission electron microscopy stereo-images were obtained showing the interior structure of casein micelles. On the basis of our interpretation of these images, an interlocked lattice model was developed in which both casein-calcium phosphate aggregates and casein polymer chains act together to maintain casein micelle integrity. The caseins form linear and branched chains (2 to 5 proteins long) interlocked by the casein-stabilized calcium phosphate nanoclusters. This model suggests that stabilization of calcium phosphate nanoclusters by phosphoserine domains of alpha(s1)-, alpha(s2)-, or beta-casein, or their combination, would orient their hydrophobic domains outward, allowing interaction and binding to other casein molecules. Other interactions between the caseins, such as calcium bridging, could also occur and further stabilize the supramolecule. The combination of having an interlocked lattice structure and multiple interactions results in an open, sponge-like colloidal supramolecule that is resistant to spatial changes and disintegration. Hydrophobic interactions between caseins surrounding a calcium phosphate nanocluster would prevent complete dissociation of casein micelles when the calcium phosphate nanoclusters are solubilized. Likewise, calcium bridging and other electrostatic interactions between caseins would prevent dissociation of the casein micelles into casein-calcium phosphate nanocluster aggregates when milk is cooled or urea is added to milk, and hydrophobic interactions are reduced. The appearance of both polymer chains and small aggregate particles during milk synthesis would also be expected based on this interlocked lattice model of casein micelles, and its supramolecule structure thus exhibits the principles of self-aggregation, interdependence, and diversity observed in nature.

Aripiprazole-Loaded Polymeric Micelles: Fabrication, Optimization and Evaluation using Response Surface Method.

PubMed

Patil, Payal Hasmukhlal; Wankhede, Pooja R; Mahajan, H S; Zawar, Laxmikant

2018-01-04

The fundamental objective of current study was to encapsulate Ari-piprazole (ARP) within Pluronic F127 micelles to improve its aqueous solubility. The recent patents on Ar-ipiprazole (JP2013136621) and micelles (WO2016004369A1) facilitated selection of drug and polymer. The drug-laden micelles were fabricated using thin-film hydration technique. Optimization of the micellar formulation was done by using response surface method (RSM). The Pluronic F127 concentration of 150 mg and 75 rpm rotational speed of rotary evaporator were found to be optimized conditions for formulating micelles. The prepared batches were further characterized for PDI (polydispersity index), zeta potential, % DLC (% Drug loading content), % EE (% Entrapment Efficiency) and % drug release study; results of these parameters were found to be 0.228, −4.04 mV and 76.50 % and 18.56 % respectively. It was observed from the In vitro release study that 97.37 ± 1.81 % drug had released from micelles after 20 hrs which were found about thrice as compared to that of pure drug. The optimized ARP micellar for-mulation was characterized using DSC (Differential Scanning Colorimetry), FT-IR (Fourier Trans-formed Infrared Spectroscopy), P-XRD (Powdered X-ray Diffraction Study) and TEM (Transmission Electronic Microscopy) studies. ARP-loaded micelles displayed a hydrodynamic diameter of 170.3 nm and a sphere-shaped morphology as determined by dynamic light scattering as well as TEM study. It is concluded that the prepared polymeric micellar system has an excellent potential to be used as a delivery carrier for Aripiprazole with increased solubility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Complex coacervation of supercharged proteins with polyelectrolytes.

PubMed

Obermeyer, Allie C; Mills, Carolyn E; Dong, Xue-Hui; Flores, Romeo J; Olsen, Bradley D

2016-04-21

Complexation of proteins with polyelectrolytes or block copolymers can lead to phase separation to generate a coacervate phase or self-assembly of coacervate core micelles. However, many proteins do not coacervate at conditions near neutral pH and physiological ionic strength. Here, protein supercharging is used to systematically explore the effect of protein charge on the complex coacervation with polycations. Four model proteins were anionically supercharged to varying degrees as quantified by mass spectrometry. Proteins phase separated with strong polycations when the ratio of negatively charged residues to positively charged residues on the protein (α) was greater than 1.1-1.2. Efficient partitioning of the protein into the coacervate phase required larger α (1.5-2.0). The preferred charge ratio for coacervation was shifted away from charge symmetry for three of the four model proteins and indicated an excess of positive charge in the coacervate phase. The composition of protein and polymer in the coacervate phase was determined using fluorescently labeled components, revealing that several of the coacervates likely have both induced charging and a macromolecular charge imbalance. The model proteins were also encapsulated in complex coacervate core micelles and micelles formed when the protein charge ratio α was greater than 1.3-1.4. Small angle neutron scattering and transmission electron microscopy showed that the micelles were spherical. The stability of the coacervate phase in both the bulk and micelles improved to increased ionic strength as the net charge on the protein increased. The micelles were also stable to dehydration and elevated temperatures.

Neutral Polymeric Micelles for RNA Delivery

PubMed Central

Lundy, Brittany B.; Convertine, Anthony; Miteva, Martina; Stayton, Patrick S.

2013-01-01

RNA interference (RNAi) drugs have significant therapeutic potential but delivery systems with appropriate efficacy and toxicity profiles are still needed. Here, we describe a neutral, ampholytic polymeric delivery system based on conjugatable diblock polymer micelles. The diblock copolymer contains a hydrophilic poly[N-(2-hydroxypropyl) methacrylamide-co-N-(2-(pyridin-2- yldisulfanyl)ethyl)methacrylamide) (poly[HPMA-co-PDSMA]) segment to promote aqueous stability and facilitate thiol-disulfide exchange reactions, and a second ampholytic block composed of propyl acrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The poly[(HPMA-co-PDSMA)-b-(PAA-co-DMAEMA-co-BMA)] was synthesized using Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization with an overall molecular weight of 22,000 g/mol and a PDI of 1.88. Dynamic light scattering and fluorescence measurements indicated that the diblock copolymers self-assemble under aqueous conditions to form polymeric micelles with a hydrodynamic radius and critical micelle concentration of 25 nm and 25 μg/mL respectively. Red blood cell hemolysis experiments show that the neutral hydrophilic micelles have potent membrane destabilizing activity at endosomal pH values. Thiolated siRNA targeting glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was directly conjugated to the polymeric micelles via thiol exchange reactions with the pyridal disulfide groups present in the micelle corona. Maximum silencing activity in HeLa cells was observed at a 1:10 molar ratio of siRNA to polymer following a 48 h incubation period. Under these conditions 90 % mRNA knockdown and 65 % and protein knockdown of at 48 h was achieved with negligible toxicity. In contrast the polymeric micelles lacking a pH-responsive endosomalytic segment demonstrated negligible mRNA and protein knockdown under these conditions. The potent mRNA knockdown and excellent biocompatibility of the neutral siRNA conjugates demonstrate the potential utility if this carrier design for delivering therapeutic siRNA drugs. PMID:23360541

Tumor-targeting peptide conjugated pH-responsive micelles as a potential drug carrier for cancer therapy.

PubMed

Wu, Xiang Lan; Kim, Jong Ho; Koo, Heebeom; Bae, Sang Mun; Shin, Hyeri; Kim, Min Sang; Lee, Byung-Heon; Park, Rang-Woon; Kim, In-San; Choi, Kuiwon; Kwon, Ick Chan; Kim, Kwangmeyung; Lee, Doo Sung

2010-02-17

Herein, we prepared tumor-targeting peptide (AP peptide; CRKRLDRN) conjugated pH-responsive polymeric micelles (pH-PMs) in cancer therapy by active and pH-responsive tumor targeting delivery systems, simultaneously. The active tumor targeting and tumoral pH-responsive polymeric micelles were prepared by mixing AP peptide conjugated PEG-poly(d,l-lactic acid) block copolymer (AP-PEG-PLA) into the pH-responsive micelles of methyl ether poly(ethylene glycol) (MPEG)-poly(beta-amino ester) (PAE) block copolymer (MPEG-PAE). These mixed amphiphilic block copolymers were self-assembled to form stable AP peptide-conjugated and pH-responsive AP-PEG-PLA/MPEG-PAE micelles (AP-pH-PMs) with an average size of 150 nm. The AP-pH-PMs containing 10 wt % of AP-PEG-PLA showed a sharp pH-dependent micellization/demicellization transition at the tumoral acid pH. Also, they presented the pH-dependent drug release profile at the acidic pH of 6.4. The fluorescence dye, TRITC, encapsulated AP-pH-PMs (TRITC-AP-pH-PMs) presented the higher tumor-specific targeting ability in vitro cancer cell culture system and in vivo tumor-bearing mice, compared to control pH-responsive micelles of MPEG-PAE. For the cancer therapy, the anticancer drug, doxorubicin (DOX), was efficiently encapsulated into the AP-pH-PMs (DOX-AP-pH-PMs) with a higher loading efficiency. DOX-AP-pH-PMs efficiently deliver anticancer drugs in MDA-MB231 human breast tumor-bearing mice, resulted in excellent anticancer therapeutic efficacy, compared to free DOX and DOX encapsulated MEG-PAE micelles, indicating the excellent tumor targeting ability of AP-pH-PMs. Therefore, these tumor-targeting peptide-conjugated and pH-responsive polymeric micelles have great potential application in cancer therapy.

Exploring the intermolecular interactions acting in solvent-modified MEKC by Molecular Dynamics and NMR: The effect of n-butanol on the separation of diclofenac and its impurities.

PubMed

Caprini, Claudia; Pasquini, Benedetta; Melani, Fabrizio; Del Bubba, Massimo; Giuffrida, Alessandro; Calleri, Enrica; Orlandini, Serena; Furlanetto, Sandra

2018-02-05

An integrated approach involving CE experiments, Molecular Dynamics (MD) simulations and two-dimensional NOE spectroscopy (2D-NOESY) experiments was employed to elucidate the intermolecular interactions and the separation mechanisms involved in a solvent-modified MEKC method for the simultaneous determination of diclofenac sodium and its impurities. The CE findings indicated that the addition of n-butanol (nBuOH) to the SDS micellar solution played a primary role for controlling the partitioning into the mixed micelles and the migration of the analytes and that the presence of nBuOH as cosurfactant was compulsory for achieving the complete separation of the compounds. The different capacity factors of the analytes were calculated and a change in solute association with the mixed micelle when changing the SDS/nBuOH molar ratio was highlighted. The optimal SDS/nBuOH molar ratio for the electrophoretic separation was 1:8. On the other hand, both MD simulations and NMR experiments indicated that the most favorable molar ratio for the formation of mixed SDS/nBuOH micelles was 1:2. These results suggested that probably there is an excess of nBuOH in the background electrolyte, both as free molecules and in form of aggregates, which is able to interact with the analytes, and thus may compete with mixed micelles for the considered compounds. The calculated values of gain in potential energy of the analytes when included in mixed micelles were in agreement with the observed migration order of the compounds. The role of methyl-β-cyclodextrin (MβCyD) in the background electrolyte was also investigated, since the addition of this CyD to the solvent-modified MEKC system was found to be useful to reduce the analysis time. MD simulations and 2D-NOESY spectra highlighted the formation of inclusion complexes with MβCyD not only with the analytes, but also with SDS. MβCyD may lower the availability of both SDS and nBuOH for forming micelles and mostly may compete with the mixed micelle as a second pseudostationary phase. Copyright © 2017 Elsevier B.V. All rights reserved.

Liposome formation in microgravity.

PubMed

Claassen, D E; Spooner, B S

1996-01-01

Liposomes are artificial vesicles with a phospholipid bilayer membrane. The formation of liposomes is a self-assembly process that is driven by the amphipathic nature of phospholipid molecules and can be observed during the removal of detergent from phospholipids dissolved in detergent micelles. As detergent concentration in the mixed micelles decreases, the non-polar tail regions of phospholipids produce a hydrophobic effect that drives the micelles to fuse and form planar bilayers in which phospholipids orient with tail regions to the center of the bilayer and polar head regions to the external surface. Remaining detergent molecules shield exposed edges of the bilayer sheet from the aqueous environment. Further removal of detergent leads to intramembrane folding and membrane folding and membrane vesiculation, forming liposomes. We have observed that the formation of liposomes is altered in microgravity. Liposomes that were formed at 1-g did not exceed 150 nm in diameter, whereas liposomes that were formed during spaceflight exhibited diameters up to 2000 nm. Using detergent-stabilized planar bilayers, we determined that the stage of liposome formation most influenced by gravity is membrane vesiculation. In addition, we found that small, equipment-induced fluid disturbances increased vesiculation and negated the size-enhancing effects of microgravity. However, these small disturbances had no effect on liposome size at 1-g, likely due to the presence of gravity-induced buoyancy-driven fluid flows (e.g., convection currents). Our results indicate that fluid disturbances, induced by gravity, influence the vesiculation of membranes and limit the diameter of forming liposomes.

Liposome formation in microgravity

NASA Astrophysics Data System (ADS)

Claassen, D. E.; Spooner, B. S.

Liposomes are artificial vesicles with a phospholipid bilayer membrane. The formation of liposomes is a self-assembly process that is driven by the amphipathic nature of phospholipid molecules and can be observed during the removal of detergent from phospholipids dissolved in detergent micelles. As detergent concentration in the mixed micelles decreases, the non-polar tail regions of phospholipids produce a hydrophobic effect that drives the micelles to fuse and form planar bilayers in which phospholipids orient with tail regions to the center of the bilayer and polar head regions to the external surface. Remaining detergent molecules shield exposed edges of the bilayer sheet from the aqueous environment. Further removal of detergent leads to intramembrane folding and membrane vesiculation, forming liposomes. We have observed that the formation of liposomes is altered in microgravity. Liposomes that were formed at 1-g did not exceed 150 nm in diameter, whereas liposomes that were formed during spaceflight exhibited diameters up to 2000 nm. Using detergent-stabilized planar bilayers, we determined that the stage of liposome formation most influenced by gravity is membrane vesiculation. In addition, we found that small, equipment-induced fluid disturbances increased vesiculation and negated the size-enhancing effects of microgravity. However, these small disturbances had no effect on liposome size at 1-g, likely due to the presence of gravity-induced buoyancy-driven fluid flows (e.g., convection currents). Our results indicate that fluid disturbances, induced by gravity, influence the vesiculation of membranes and limit the diameter of forming liposomes.

Path-integral theory of an axially confined worm-like chain

NASA Astrophysics Data System (ADS)

Smith, D. A.

2001-06-01

A path-integral formulation is developed for the thermodynamic properties of a worm-like chain moving on a surface and laterally confined by a harmonic potential. The free energy of the chain is calculated as a function of its length and boundary conditions at each end. Distribution functions for chain displacements can be constructed by utilizing the Markov property as a function of displacement φ(s) and its derivative dφ(s)/ds along the path. These quantities are also calculated in the presence of pinning sites which impose fixed positive or negative displacements, foreshadowing their application to a model for the regulation of striated muscle.

Interfacial instability of wormlike micellar solutions sheared in a Taylor-Couette cell

NASA Astrophysics Data System (ADS)

Mohammadigoushki, Hadi; Muller, Susan J.

2014-11-01

We report experiments on wormlike micellar solutions sheared in a custom-made Taylor-Couette (TC) cell. The computer controlled TC cell allows us to rotate both cylinders independently. Wormlike micellar solutions containing water, CTAB, and NaNo3 with different compositions are highly elastic and exhibit shear banding. We visualized the flow field in the θ-z as well as r-z planes, using multiple cameras. When subject to low shear rates, the flow is stable and azimuthal, but becomes unstable above a certain threshold shear rate. This shear rate coincides with the onset of shear banding. Visualizing the θ-z plane shows that this instability is characterized by stationary bands equally spaced in the z direction. Increasing the shear rate results to larger wave lengths. Above a critical shear rate, experiments reveal a chaotic behavior reminiscent of elastic turbulence. We also studied the effect of ramp speed on the onset of instability and report an acceleration below which the critical Weissenberg number for onset of instability is unaffected. Moreover, visualizations in the r-z direction reveals that the interface between the two bands undulates with shear bands evolving towards the outer cylinder regardless of which cylinder is rotating.

Inhibition of atherosclerosis-promoting microRNAs via targeted polyelectrolyte complex micelles

PubMed Central

Kuo, Cheng-Hsiang; Leon, Lorraine; Chung, Eun Ji; Huang, Ru-Ting; Sontag, Timothy J.; Reardon, Catherine A.; Getz, Godfrey S.; Tirrell, Matthew; Fang, Yun

2015-01-01

Polyelectrolyte complex micelles have great potential as gene delivery vehicles because of their ability to encapsulate charged nucleic acids forming a core by neutralizing their charge, while simultaneously protecting the nucleic acids from non-specific interactions and enzymatic degradation. Furthermore, to enhance specificity and transfection efficiency, polyelectrolyte complex micelles can be modified to include targeting capabilities. Here, we describe the design of targeted polyelectrolyte complex micelles containing inhibitors against dys-regulated microRNAs (miRNAs) that promote atherosclerosis, a leading cause of human mortality and morbidity. Inhibition of dys-regulated miRNAs in diseased cells associated with atherosclerosis has resulted in therapeutic efficacy in animal models and has been proposed to treat human diseases. However, the non-specific targeting of microRNA inhibitors via systemic delivery has remained an issue that may cause unwanted side effects. For this reason, we incorporated two different peptide sequences to our miRNA inhibitor containing polyelectrolyte complex micelles. One of the peptides (Arginine-Glutamic Acid-Lysine-Alanine or REKA) was used in another micellar system that demonstrated lesion-specific targeting in a mouse model of atherosclerosis. The other peptide (Valine-Histidine-Proline-Lysine-Glutamine-Histidine-Arginine or VHPKQHR) was identified via phage display and targets vascular endothelial cells through the vascular cell adhesion molecule-1 (VCAM-1). In this study we have tested the in vitro efficacy and efficiency of lesion- and cell-specific delivery of microRNA inhibitors to the cells associated with atherosclerotic lesions via peptide-targeted polyelectrolyte complex micelles. Our results show that REKA-containing micelles (fibrin-targeting) and VHPKQHR-containing micelles (VCAM-1 targeting) can be used to carry and deliver microRNA inhibitors into macrophages and human endothelial cells, respectively. Additionally, the functionality of miRNA inhibitors in cells was demonstrated by analyzing miRNA expression as well as the expression or the biological function of its downstream target protein. Our study provides the first demonstration of targeting dys-regulated miRNAs in atherosclerosis using targeted polyelectrolyte complex micelles and holds promising potential for translational applications. PMID:25685357

Structure and Conductivity of Semiconducting Polymer Hydrogels.

PubMed

Huber, Rachel C; Ferreira, Amy S; Aguirre, Jordan C; Kilbride, Daniel; Toso, Daniel B; Mayoral, Kenny; Zhou, Z Hong; Kopidakis, Nikos; Rubin, Yves; Schwartz, Benjamin J; Mason, Thomas G; Tolbert, Sarah H

2016-07-07

Poly(fluorene-alt-thiophene) (PFT) is a conjugated polyelectrolyte that self-assembles into rod-like micelles in water, with the conjugated polymer backbone running along the length of the micelle. At modest concentrations (∼10 mg/mL in aqueous solutions), PFT forms hydrogels, and this work focuses on understanding the structure and intermolecular interactions in those gel networks. The network structure can be directly visualized using cryo electron microscopy. Oscillatory rheology studies further tell us about connectivity within the gel network, and the data are consistent with a picture where polymer chains bridge between micelles to hold the network together. Addition of tetrahydrofuran (THF) to the gels breaks those connections, but once the THF is removed, the gel becomes stronger than it was before, presumably due to the creation of a more interconnected nanoscale architecture. Small polymer oligomers can also passivate the bridging polymer chains, breaking connections between micelles and dramatically weakening the hydrogel network. Fits to solution-phase small-angle X-ray scattering data using a Dammin bead model support the hypothesis of a bridging connection between PFT micelles, even in dilute aqueous solutions. Finally, time-resolved microwave conductivity measurements on dried samples show an increase in carrier mobility after THF annealing of the PFT gel, likely due to increased connectivity within the polymer network.

Self-assembly of model graft copolymers of agarose and weak polyelectrolyte-based amphiphilic diblock copolymers: controlled drug release and degradation.

PubMed

Muppalla, Ravikumar; Jewrajka, Suresh K; Prasad, Kamalesh

2013-06-01

Polysaccharide-based copolymers are promising biomaterials due to their biocompatibility and biodegradability. For potential biomedical applications the copolymer as a whole and all the degraded species must be biocompatible and easily removable from the system. In this regards, new model pH-responsive seaweed agarose (Agr) grafted with weak polyelectrolyte-based well-defined amphiphilic block copolymers ca. poly[(methyl methacrylate)-b-(2-dimethylamino)ethyl methacrylate)] (PMMA-b-PDMA) were designed and synthesized to study the self-assembly, degradation, and in vitro hydrophobic/hydrophilic drug release behavior. The graft copolymer solutions display extremely low critical micelle concentration (CMC) and form pH responsive stable micelles. The degradation study of the graft copolymer reveals that the entire degraded components are well soluble/dispersible in water due to formation of mixed micelles. The micelles are also strongly adsorbed on the mica surface owing to electrostatic interaction. One application of the graft copolymer micelles is that it can entrap both hydrophilic and poorly water soluble hydrophobic drugs effectively and exhibit slow release kinetics. The release kinetics of both the hydrophilic and poorly water soluble hydrophobic drugs change with pH as well as with the composition of the graft copolymer. Copyright © 2012 Wiley Periodicals, Inc.

A new model to study the phase transition from microstructures to nanostructures in ionic/ionic surfactants mixture.

PubMed

Sohrabi, Beheshteh; Gharibi, Hussein; Javadian, Soheila; Hashemianzadeh, Majid

2007-08-30

The phase behavior and aggregate structures of mixtures of the oppositely charged surfactants cetyltrimethyl ammonium bromide (CTAB) and sodium dodecyl sulfate (SDS) are explored at high dilution by pulsed field gradient stimulated echo (PFG-STE) NMR. The aggregation numbers and hydrodynamic radii of vesicles and mixed micelles were determined by a combination of viscosity and self-diffusion coefficient measurements. The average size of the mixed micelles was larger than that of micelles containing uniformly charged head groups. Analysis of the variations of the self-diffusion coefficient and viscosity with changing concentration of CTAB or SDS in the cationic-rich and anionic-rich regions revealed a phase transition from vesicles to mixed micelles. Differences in the lengths of the CTAB and SDS hydrophobic chains stabilize vesicles relative to other microstructures (e.g., liquid crystalline and precipitate phase), and vesicles form spontaneously over a wide range of compositions in both cationic-rich and anionic-rich solutions. The results obtained from conductometry measurements confirmed this transition. Finally, according to the capacitor model, a new model was developed for estimating the surface potentials and electrostatic free energy (g(elec)). Then we investigated the variations of electrostatic and transfer free energy in phase transition between mixed micelle and vesicle.

Rapid analysis of water- and fat-soluble vitamins by electrokinetic chromatography with polymeric micelle as pseudostationary phase.

PubMed

Ni, Xinjiong; Xing, Xiaoping; Cao, Yuhua; Cao, Guangqun

2014-11-28

A novel polymeric micelle, formed by random copolymer poly (stearyl methacrylate-co-methacrylic acid) (P(SMA-co-MAA)) has been used as pseudostationary phase (PSP) in electrokinetic chromatography (EKC) for simultaneous and rapid determination of 11 kinds of water- and fat-soluble vitamins in this work. The running buffer consisting of 1% (w/v) P(SMA-co-MAA), 10% (v/v) 1-butanol, 20% (v/v) acetonitrile, and 30 mM Palitzsch buffer solution (pH 9.2) was applied to improve the selectivity and efficiency, as well as to shorten analysis time. 1-Butanol and acetonitrile as the organic solvent modifiers played the most important roles for rapid separation of these vitamins. The effects of organic solvents on microstructure of the polymeric micelle were investigated. The organic solvents swell the polymeric micelle by three folds, lower down the surface charge density and enhance the microenviromental polarity of the polymeric micelle. The 11 kinds of water- and fat-soluble vitamins could be baseline separated within 13 min. The method was applied to determine water- and fat-soluble vitamins in commercial vitamin sample; the recoveries were between 93% and 111% with the relative standard derivations (RSDs) less than 5%. The determination results matched the label claim. Copyright © 2014 Elsevier B.V. All rights reserved.

Controlling block copolymer phase behavior using ionic surfactant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ray, D.; Aswal, V. K.

2016-05-23

The phase behavior of poly(ethylene oxide)-poly(propylene oxide-poly(ethylene oxide) PEO-PPO-PEO triblock copolymer [P85 (EO{sub 26}PO{sub 39}EO{sub 26})] in presence of anionic surfactant sodium dodecyl sulfate (SDS) in aqueous solution as a function of temperature has been studied using dynamic light scattering (DLS) and small-angle neutron scattering (SANS). The measurements have been carried out for fixed concentrations (1 wt%) of block copolymer and surfactants. Each of the individual components (block copolymer and surfactant) and the nanoparticle–surfactant mixed system have been examined at varying temperature. The block copolymer P85 forms spherical micelles at room temperature whereas shows sphere-to-rod like micelle transition at highermore » temperatures. On the other hand, SDS surfactant forms ellipsoidal micelles over a wide temperature range. Interestingly, it is found that phase behavior of mixed micellar system (P85 + SDS) as a function of temperature is drastically different from that of P85, giving the control over the temperature-dependent phase behavior of block copolymers.« less

Affinity Chromatography in Nonionic Detergent Solutions

NASA Astrophysics Data System (ADS)

Robinson, Jack B.; Strottmann, James M.; Wick, Donald G.; Stellwagen, Earle

1980-10-01

Anionic dye affinity chromatography is commonly unproductive in the presence of nonionic detergents used to extract particulate proteins. Using lactate dehydrogenase as a model protein, Cibacron blue F3GA as a model dye, and Triton X-100 as a model detergent, we find that the dye is encapsulated in nonionic detergent micelles, rendering the dye incapable of ligation with the enzyme. However, the dye can be liberated from the micelles without altering the nonionic detergent concentration by addition of an anionic detergent, such as deoxycholate or sodium dodecyl sulfate, forming mixed anionic/nonionic micelles that displace the anionic dye. Encapsulation of the anionic detergents prevents their activity as protein denaturants. These observations have been successfully translated to the dye affinity chromatography of a detergent extract of brain particulate cyclic nucleotide phosphodiesterase.

Lactose-installed poly(ethylene glycol)-poly(d,l-lactide) block copolymer micelles exhibit fast-rate binding and high affinity toward a protein bed simulating a cell surface. A surface plasmon resonance study.

PubMed

Jule, Eduardo; Nagasaki, Yukio; Kataoka, Kazunori

2003-01-01

Lactose molecules were installed on the surface of poly(ethylene glycol)-poly(d,l-lactide) (PEG-PLA) block copolymer micelles in the scope of seeking specific recognition by cell surface receptors at hepatic sites. This, in turn, is expected to result in the formation of a complex displaying prolonged retention times and thus enhanced cellular internalization by receptor-mediated endocytosis. The so-obtained particles based on a block copolymer of molecular weight 9400 g/mol (4900/4500 g/mol for the PEG and PLA blocks, respectively) were found to have an average hydrodynamic diameter of 31.8 nm, as measured by dynamic light scattering. Further, the particle size distribution (micro(2)/Gamma(2)) was found to be lower than 0.08. Lactose-PEG-PLA micelles (Lac-micelles) were then injected over a gold surface containing Ricinus communis agglutinin lectins simulating the aforementioned glycoreceptors, and their interaction was studied by surface plasmon resonance. Then, a kinetic evaluation was carried out, by fitting the observed data mathematically. It appears that Lac-micelles bind in a multivalent manner to the lectin protein bed, which logically results in low dissociation constants. Micelles bearing a ligand density of 80% (Lac-micelles 80%: 80 lactose molecules per 100 copolymer chains) exhibit fast association phases (k(a1) = 3.2 x 10(4) M(-)(1) s(-)(1)), but also extremely slow dissociation phases (k(d1) = 1.3 x 10(-)(4) s(-)(1)). Recorded sensorgrams were fitted with a trivalent model, conveying a calculated equilibrium dissociation constant (K(D1) = k(d1)/k(a1)) of about 4 nM. The importance of cooperative binding was also assessed, by preparing Lac-micelles bearing different ligand densities, and by discussing the influence of the latter on kinetic constants. Interestingly enough, whereas Lac-micelles 80% bind in a trivalent manner to the protein bed, Lac-micelles 20% are still capable of forming bivalent complexes with the same protein bed (K(D1) = 1360 nM). Therefore, despite enhanced kinetic values brought about by a supplementary bond, lower ligand densities appear to be more effective on a molecular basis.

Front-End Processing of Cell Lysates for Enhanced Chip-Based Detection

DTIC Science & Technology

2006-07-28

manipulation used in lab-on-a-chip devices. A small unknown sample is first mixed with the PNA surfactants (“PNAA”) to tag the DNA targets, and then the...unknown sample is first mixed with the PNA surfactants (hereafter referred to as “PNA amphiphiles” or “PNAA”) to tag the DNA targets, and then the...prolate ellipsoid, and mixed PNAA/SDS micelles form spherical micelles. On addition of complementary DNA, the PNAA/DNA duplexes do not participate in

Insights into molecular architecture of terpenes using small angle neutron scattering

NASA Astrophysics Data System (ADS)

Rai, Durgesh K.; Annamraju, Aparna; Pingali, Sai Venkatesh; O'Neill, Hugh M.; Mewalal, Ritesh; Gunter, Lee E.; Tuskan, Gerald A.

Understanding macromolecular architectures is vital to engineering prospective terpene candidates for advanced biofuels. Eucalyptus plants store terpenes in specialized cavity-like structures in the leaves called oil glands, which comprises of volatile (VTs) and non-volatile (NVTs) terpenes. Using small-angle neutron scattering, we have investigated the structure and phase behavior of the supramolecular assembly formed by Geranyl beta-D-glucoside (GDG), a NVT and compare the results with that of beta-octyl glucoside (BOG). The formation of micellar structures was observed in the concentration range of 0.5-5 v/v% in water using small angle neutron scattering (SANS) where Schultz sphere model was used in quantifying structural parameters of micelles. SANS studies determine that GDG and BOG behave like amphiphiles forming micellar structures in aqueous solution. The micelles swell upon addition of alpha-Pinene (AP) indicating partition to the core region of the micelles. The general behavior of the micellar growth after partitioning of AP to form thermodynamically stable sizes varies with the NVT concentration. Our studies reveal that the presence of steric hindrance in the GDG via the unsaturated bonds could help stabilize VTs inside the oil glands. LDRD project LOIS ID 7428, SNS, CSMB, HFIR, ORNL, DOE Office of Science User Facilities.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chillura-Martino, D; Triolo, R.; McClain, J.B.

1995-12-31

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 secondmore » 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}.« less

Sans study of reverse micelles formed upon extraction of inorganic acids by TBP in n-octane.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiarizia, R.; Briand, A.; Jensen, M. P.

2008-01-01

Small-angle neutron scattering (SANS) data for n-octane solutions of TBP loaded with progressively larger amounts of HNO{sub 3}, HClO{sub 4}, H{sub 2}SO{sub 4}, and H{sub 3}PO{sub 4} up to and beyond the LOC (limiting organic concentration of acid) condition, were interpreted using the Baxter model for hard spheres with surface adhesion. The coherent picture of the behavior of the TBP solutions derived from the SANS investigation discussed in this paper confirmed our recently developed model for third phase formation. This model analyses the features of the scattering data in the low Q region as arising from van der Waals interactionsmore » between the polar cores of reverse micelles. Our SANS data indicated that the TBP micelles swell when acid and water are extracted into their polar core. The swollen micelles have critical diameters ranging from 15 to 22 {angstrom}, and polar core diameters between 10 and 15 {angstrom}, depending on the specific system. At the respective LOC conditions, the TBP weight-average aggregation numbers are -4 for HClO{sub 4}, -6 for H2SO{sub 4}, -7 for HCl, and -10 for H{sub 3}PO{sub 4}. The comparison between the behavior of HNO{sub 3}, a non-third phase forming acid, and the other acids provided an explanation of the effect of the water molecules present in the polar core of the micelles on third phase formation. The thickness of the lipophilic shell of the micelles indicated that the butyl groups of TBP lie at an angle of -25 degrees relative to a plane tangent to the micellar core. The critical energy of intermicellar attraction, U(r), was about -2 k{sub B}T for all the acids investigated. This value is the same as that reported in our previous publications on the extraction of metal nitrates by TBP, confirming that the same mechanism and energetics are operative in the formation of a third phase, independent of whether the chemical species extracted are metal nitrate salts or inorganic acids.« less

Systematic analysis of protein–detergent complexes applying dynamic light scattering to optimize solutions for crystallization trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meyer, Arne; Dierks, Karsten; XtalConcepts, Marlowring 19, 22525 Hamburg

Application of in situ dynamic light scattering to solutions of protein–detergent complexes permits characterization of these complexes in samples as small as 2 µl in volume. Detergents are widely used for the isolation and solubilization of membrane proteins to support crystallization and structure determination. Detergents are amphiphilic molecules that form micelles once the characteristic critical micelle concentration (CMC) is achieved and can solubilize membrane proteins by the formation of micelles around them. The results are presented of a study of micelle formation observed by in situ dynamic light-scattering (DLS) analyses performed on selected detergent solutions using a newly designed advancedmore » hardware device. DLS was initially applied in situ to detergent samples with a total volume of approximately 2 µl. When measured with DLS, pure detergents show a monodisperse radial distribution in water at concentrations exceeding the CMC. A series of all-transn-alkyl-β-d-maltopyranosides, from n-hexyl to n-tetradecyl, were used in the investigations. The results obtained verify that the application of DLS in situ is capable of distinguishing differences in the hydrodynamic radii of micelles formed by detergents differing in length by only a single CH{sub 2} group in their aliphatic tails. Subsequently, DLS was applied to investigate the distribution of hydrodynamic radii of membrane proteins and selected water-insoluble proteins in presence of detergent micelles. The results confirm that stable protein–detergent complexes were prepared for (i) bacteriorhodopsin and (ii) FetA in complex with a ligand as examples of transmembrane proteins. A fusion of maltose-binding protein and the Duck hepatitis B virus X protein was added to this investigation as an example of a non-membrane-associated protein with low water solubility. The increased solubility of this protein in the presence of detergent could be monitored, as well as the progress of proteolytic cleavage to separate the fusion partners. This study demonstrates the potential of in situ DLS to optimize solutions of protein–detergent complexes for crystallization applications.« less

Structure and dynamics of micelle-bound neuropeptide Y: comparison with unligated NPY and implications for receptor selection.

PubMed

Bader, R; Bettio, A; Beck-Sickinger, A G; Zerbe, O

2001-01-12

The biological importance of the neuropeptide Y (NPY) has steered a number of investigations about its solution structure over the last 20 years. Here, we focus on the comparison of the structure and dynamics of NPY free in solution to when bound to a membrane mimetic, dodecylphosphocholine (DPC) micelles, as studied by 2D (1)H NMR spectroscopy. Both, free in solution and in the micelle-bound form, the N-terminal segment (Tyr1-Glu15) is shown to extend like a flexible tail in solution. This is not compatible with the PP-fold model for NPY that postulates backfolding of the flexible N terminus onto the C-terminal helix. The correlation time (tau(c)) of NPY in aqueous solution, 5.5 (+/-1.0) ns at 32 degrees C, is only consistent with its existence in a dimeric form. Exchange contributions especially enhancing transverse relaxation rates (R(2)) of residues located on one side of the C-terminal helix of the molecule are supposed to originate from dimerization of the NPY molecule. The dimerization interface was directly probed by looking at (15)N-labeled NPY/spin-labeled [TOAC34]-[(14)N]-NPY heterodimers and revealed both parallel and anti-parallel alignment of the helices. The NMR-derived three-dimensional structure of micelle-bound NPY at 37 degrees C and pH 6.0 is similar but not identical to that free in solution. The final set of 17 lowest-energy DYANA structures is particularly well defined in the region of residues 21-31, with a mean pairwise RMSD of 0.23 A for the backbone heavy atoms and 0.85 A for all heavy atoms. The combination of NMR relaxation data and CD measurements clearly demonstrates that the alpha-helical region Ala18-Thr32 is more stable, and the C-terminal tetrapeptide becomes structured only in the presence of the phosphocholine micelles. The position of NPY relative to the DPC micelle surface was probed by adding micelle integrating spin labels. Together with information from (1)H,(2)H exchange rates, we conclude that the interaction of NPY with the micelle is promoted by the amphiphilic alpha-helical segment of residues Tyr21-Thr32. NPY is located at the lipid-water interface with its C-terminal helix parallel to the membrane surface and penetrates the hydrophobic interior only via insertions of a few long aliphatic or aromatic side-chains. From these data we can demonstrate that the dimer interface of neuropeptide Y is similar to the interface of the monomer binding to DPC-micelles. We speculate that binding of the NPY monomer to the membrane is an essential key step preceeding receptor binding, thereby pre-orientating the C-terminal tetrapeptide and possibly inducing the bio-active conformation. Copyright 2001 Academic Press.

Internal Structure of 15 nm 3-Helix Micelle Revealed by Small-Angle Neutron Scattering and Coarse-Grained MD Simulation.

PubMed

Ang, JooChuan; Ma, Dan; Lund, Reidar; Keten, Sinan; Xu, Ting

2016-10-10

3-Helix micelles (3HM) formed by self-assembly of peptide-polymer conjugate amphiphiles have shown promise as a nanocarrier platform due to their long-circulation, deep tumor penetration, selective accumulation in tumor, and ability to cross the blood-brain barrier (BBB) for glioblastoma therapy. There is a need to understand the structural contribution to the high in vivo stability and performance of 3HM. Using selective deuteration, the contrast variation technique in small-angle neutron scattering, and coarse-grained molecular dynamics simulation, we determined the spatial distribution of each component within 3HM. Our results show a slightly deformed polyethylene glycol (PEG) conformation within the micelle that is radially offset from its conjugation site toward the exterior of the micelle and a highly solvated shell. Surprisingly, ∼85 v/v % of 3HM is water, unusually higher than any micellar nanocarrier based on our knowledge. The result will provide important structural insights for future studies to uncover the molecular origin of 3HM's in vivo performance, and development of the nanocarriers.

Endophilin-A1 BAR domain interaction with arachidonyl CoA.

PubMed

Petoukhov, Maxim V; Weissenhorn, Winfried; Svergun, Dmitri I

2014-01-01

Endophilin-A1 belongs to the family of BAR domain containing proteins that catalyze membrane remodeling processes via sensing, inducing and stabilizing membrane curvature. We show that the BAR domain of endophilin-A1 binds arachidonic acid and molds its coenzyme A (CoA) activated form, arachidonyl-CoA into a defined structure. We studied low resolution structures of endophilin-A1-BAR and its complex with arachidonyl-CoA in solution using synchrotron small-angle X-ray scattering (SAXS). The free endophilin-A1-BAR domain is shown to be dimeric at lower concentrations but builds tetramers and higher order complexes with increasing concentrations. Extensive titration SAXS studies revealed that the BAR domain produces a homogenous complex with the lipid micelles. The structural model of the complexes revealed two arachidonyl-CoA micelles bound to the distal arms of an endophilin-A1-BAR dimer. Intriguingly, the radius of the bound micelles significantly decreases compared to that of the free micelles, and this structural result may provide hints on the potential biological relevance of the endophilin-A1-BAR interaction with arachidonyl CoA.

pH-responsive nanoparticle assembly from peptide amphiphiles for tumor targeting drug delivery.

PubMed

Chang, Cong; Liang, Peiqing; Chen, Linlin; Liu, Junfeng; Chen, Shihong; Zheng, Guohua; Quan, Changyun

2017-09-01

In this paper, the peptide amphiphiles (PA) which consists of RGDSEEEEEEEEEEK as pH-sensitive segment and stearic acid as hydrophobic segment named RGDS-E 10 -Lys(C 18 ) was successfully synthesized. TEM images showed that uniformly dispersed nanoparticles could be formed by PA molecules in pH 7.4 medium, however, disintegrated in pH 5.0 medium. Circular dichroism (CD) spectrum indicated that polypeptide adopted a random-coil conformation in neutral medium (pH 7.4). The CD signal was significantly attenuate for decreased solubility of PA in medium with pH 5.0. As expected, the prepared RGDS-E 10 -Lys(C 18 ) assembly showed high pH-sensitive property which demonstrated a much more rapid drug release from micelles in tumor tissue (acidic environment) than in physiological environment (neutral environment). After DOX-loaded micelles incubated with tumor cells, the cytotoxicity of the micelles against Hela cells was increased obviously, indicating the great potential of micelles developed here as promising vehicle for targeted pH-responsive drug delivery.

Water dynamics at neutral and ionic interfaces

PubMed Central

Fenn, Emily E.; Wong, Daryl B.; Fayer, M. D.

2009-01-01

The orientational dynamics of water at a neutral surfactant reverse micelle interface are measured with ultrafast infrared spectroscopy of the hydroxyl stretch, and the results are compared to orientational relaxation of water interacting with an ionic interface. The comparison provides insights into the influence of a neutral vs. ionic interface on hydrogen bond dynamics. Measurements are made and analyzed for large nonionic surfactant Igepal CO-520reverse micelles (water nanopool with a 9-nm diameter). The results are compared with those from a previous study of reverse micelles of the same size formed with the ionic surfactant Aerosol-OT (AOT). The results demonstrate that the orientational relaxation times for interfacial water molecules in the two types of reverse micelles are very similar (13 ps for Igepal and 18 ps for AOT) and are significantly slower than that of bulk water (2.6 ps). The comparison of water orientational relaxation at neutral and ionic interfaces shows that the presence of an interface plays the dominant role in determining the hydrogen bond dynamics, whereas the chemical nature of the interface plays a secondary role. PMID:19706895

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zakharov, Anatoly I.; Adzhemyan, Loran Ts.; Shchekin, Alexander K., E-mail: akshch@list.ru

2015-09-28

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 takemore » 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.« less

Solubilization of polycyclic aromatic hydrocarbons in micellar nonionic surfactant solutions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Edwards, D.A.; Luthy, R.G.; Liu, Zhongbao

1991-01-01

Experimental data are presented on the enhanced apparent solubilities of naphthalene, phenanthrene, and pyrene resulting from solubilization in aqueous solutions of four commercial, nonionic surfactants: an alkyl polyoxyethylene (POE) type, two octylphenol POE types, and a nonylphenol POE type. Apparent solubilities of the polycyclic aromatic hydrocarbon (PAH) compounds in surfactant solutions were determined by radiolabeled techniques. Solubilization of each PAH compound commenced at the surfactant critical micelle concentration and was proportional to the concentration of surfactant in micelle form. The partitioning of organic compounds between surfactant micelles and aqueous solution is characterized by a mole fraction micelle-phase/aqueous-phase partition coefficient, K{submore » m}. Values of log K{sub m} for PAH compounds in surfactant solutions of this study range from 4.57 to 6.53. Log K{sub m} appears to be a linear function of log K{sub ow} for a given surfactant solution. A knowledge of partitioning in aqueous surfactant systems is a prerequisite to understanding mechanisms affecting the behavior of hydrophobic organic compounds in soil-water systems in which surfactants play a role in contaminant remediation or facilitated transport.« less

Self-Assembled Nanocarriers Based on Amphiphilic Natural Polymers for Anti- Cancer Drug Delivery Applications.

PubMed

Sabra, Sally; Abdelmoneem, Mona; Abdelwakil, Mahmoud; Mabrouk, Moustafa Taha; Anwar, Doaa; Mohamed, Rania; Khattab, Sherine; Bekhit, Adnan; Elkhodairy, Kadria; Freag, May; Elzoghby, Ahmed

2017-01-01

Micellization provides numerous merits for the delivery of water insoluble anti-cancer therapeutic agents including a nanosized 'core-shell' drug delivery system. Recently, hydrophobically-modified polysaccharides and proteins are attracting much attention as micelle forming polymers to entrap poorly soluble anti-cancer drugs. By virtue of their small size, the self-assembled micelles can passively target tumor tissues via enhanced permeation and retention effect (EPR). Moreover, the amphiphilic micelles can be exploited for active-targeted drug delivery by attaching specific targeting ligands to the outer micellar hydrophilic surface. Here, we review the conjugation techniques, drug loading methods, physicochemical characteristics of the most important amphiphilic polysaccharides and proteins used as anti-cancer drug delivery systems. Attention focuses on the mechanisms of tumor-targeting and enhanced anti-tumor efficacy of the encapsulated drugs. This review will highlight the remarkable advances of hydrophobized polysaccharide and protein micelles and their potential applications as anti-cancer drug delivery nanosystems. Micellar nanocarriers fabricated from amphiphilic natural polymers hold great promise as vehicles for anti-cancer drugs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

High temperature ultralow water content carbon dioxide-in-water foam stabilized with viscoelastic zwitterionic surfactants.

PubMed

Alzobaidi, Shehab; Da, Chang; Tran, Vu; Prodanović, Maša; Johnston, Keith P

2017-02-15

Ultralow water content carbon dioxide-in-water (C/W) foams with gas phase volume fractions (ϕ) above 0.95 (that is <0.05 water) tend to be inherently unstable given that the large capillary pressures that cause the lamellar films to thin. Herein, we demonstrate that these C/W foams may be stabilized with viscoelastic aqueous phases formed with a single zwitterionic surfactant at a concentration of only 1% (w/v) in DI water and over a wide range of salinity. Moreover, they are stable with a foam quality ϕ up to 0.98 even for temperatures up to 120°C. The properties of aqueous viscoelastic solutions and foams containing these solutions are examined for a series of zwitterionic amidopropylcarbobetaines, R-ONHC 3 H 6 N(CH 3 ) 2 CH 2 CO 2 , where R is varied from C 12 - 14 (coco) to C 18 (oleyl) to C 22 (erucyl). For the surfactants with long C 18 and C 22 tails, the relaxation times from complex rheology indicate the presence of viscoelastic wormlike micelles over a wide range in salinity and pH, given the high surfactant packing fraction. The apparent viscosities of these ultralow water content foams reached more than 120cP with stabilities more than 30-fold over those for foams formed with the non-viscoelastic C 12 - 14 surfactant. At 90°C, the foam morphology was composed of ∼35μm diameter bubbles with a polyhedral texture. The apparent foam viscosity typically increased with ϕ and then dropped at ϕ values higher than 0.95-0.98. The Ostwald ripening rate was slower for foams with viscoelastic versus non-viscoelastic lamellae as shown by optical microscopy, as a consequence of slower lamellar drainage rates. The ability to achieve high stabilities for ultralow water content C/W foams over a wide temperature range is of interest in various technologies including polymer and materials science, CO 2 enhanced oil recovery, CO 2 sequestration (by greater control of the CO 2 flow patterns), and possibly even hydraulic fracturing with minimal use of water to reduce the requirements for wastewater disposal. Copyright © 2016. Published by Elsevier Inc.

Unimolecular Micelles of Amphiphilic Cyclodextrin-Core Star-Like Copolymers with Covalent pH-Responsive Linkage of Anticancer Prodrugs.

PubMed

Jia, Tao; Huang, Shuo; Yang, Cangjie; Wang, Mingfeng

2017-08-07

Multifunctional stable and stimuli-responsive drug delivery systems are important for efficient cancer treatment due to their advantages such as enhanced cancer-targeting efficiency, improved pharmacokinetics, minimized drug leaching, and reduced undesirable side effects. Here we report a robust and pH-responsive anticancer drug delivery system based on unimolecular micelles of star-like amphiphilic copolymers. The polymers (denoted as CPOFs) were facilely synthesized via one-step atom transfer radical polymerization of functionalizable benzoaldehyde and hydrophilic poly[(oligo ethylene glycol) methyl ether methacrylate] as comonomers from the core of heptakis [2,3,6-tri-o-(2-bromo-2-methyl propionyl]-β-cyclodextrin as the initiator. Doxorubicin (DOX) as an anticancer drug was covalently linked to the benzoaldehyde groups of CPOFs through pH-sensitive Schiff-base bonds. The DOX-conjugated polymers, denoted as CPOF-DOX, formed robust unimolecular micelles with an average diameter of 18 nm in aqueous media. More importantly, these unimolecular micelles showed higher drug loading capacity and more controllable drug release characteristics, compared to our previous unimolecular micelles of β-cyclodextrin-poly(lactic acid)-b-poly[(oligo ethylene glycol) methyl ether methacrylates] that physically encapsulated DOX via hydrophobic interaction. Moreover, the CPOF-DOX unimolecular micelles could be internalized by human cervical cancer HeLa cells in a stepwise way and showed less cytotoxicity compared to carrier-free DOX. We foresee that CPOF-DOX would provide a promising robust and controllable anticancer drug delivery system for future animal study and clinical trials for cancer treatment.

Protein unfolding in detergents: effect of micelle structure, ionic strength, pH, and temperature.

PubMed Central

Otzen, Daniel E

2002-01-01

The 101-residue monomeric protein S6 unfolds in the anionic detergent sodium dodecyl sulfate (SDS) above the critical micelle concentration, with unfolding rates varying according to two different modes. Our group has proposed that spherical micelles lead to saturation kinetics in unfolding (mode 1), while cylindrical micelles prevalent at higher SDS concentrations induce a power-law dependent increase in the unfolding rate (mode 2). Here I investigate in more detail how micellar properties affect protein unfolding. High NaCl concentrations, which induce cylindrical micelles, favor mode 2. This is consistent with our model, though other effects such as electrostatic screening cannot be discounted. Furthermore, unfolding does not occur in mode 2 in the cationic detergent LTAB, which is unable to form cylindrical micelles. A strong retardation of unfolding occurs at higher LTAB concentrations, possibly due to the formation of dead-end protein-detergent complexes. A similar, albeit much weaker, effect is seen in SDS in the absence of salt. Chymotrypsin inhibitor 2 exhibits the same modes of unfolding in SDS as S6, indicating that this type of protein unfolding is not specific for S6. The unfolding process in mode 1 has an activation barrier similar in magnitude to that in water, while the activation barrier in mode 2 is strongly concentration-dependent. The strong pH-dependence of unfolding in SDS and LTAB suggests that the rate of unfolding in anionic detergent is modulated by repulsion between detergent headgroups and anionic side chains, while cationic side chains modulate unfolding rates in cationic detergents. PMID:12324439

Polymeric contrast agents for medical imaging.

PubMed

Torchilin, V P

2000-09-01

Synthetic polymers and co-polymers are described, to be used as carriers of reporter groups for gamma-, magnetic resonance (MR), and computed tomography (CT) imaging. Those compounds include polychelating and amphiphilic polymers and serve as key components of various contrast agents. Single terminus-activated polychelating polymers were synthesized using poly-L-lysine (PLL) as a main chain and chelating moieties (such as diethylene triamine pentaacetic acid or DTPA) as side groups. These polymers were used for the modification of diagnostic monoclonal antibodies to increase their load with reporter metal atoms. As a result, better images within shorter time intervals were obtained in animal experiments. The application of liposomes and micelles as carriers for diagnostic imaging agents in experimental and clinical medicine is considered. The load of liposomes and micelles with contrast agents for gamma- and MR imaging (MRI) was sharply increased by using polychelating polymers additionally modified on one end with a hydrophobic phospholipid residue to give amphiphilic polymers. Such polymers easily incorporate the liposome membrane or micelle core and provide better loading of liposomes and micelles with reporter metals and, consequently, better and faster imaging of various physiological compartments, such as lymphatic and vascular systems. A block-copolymer of methoxy-poly(ethylene glycol) (MPEG) and iodine-substituted PLL was synthesized to prepare long-circulating contrast agent for CT imaging of the blood pool. In the aqueous solution, this copolymer forms stable and heavily loaded with iodine (up to 30% of iodine by weight) micelles. These micelle were successfully used for CT visualization of the vascular network in experimental animals. General trends in developing contrast polymers are discussed.

Anisotropic reversed micelles with fluorocarbon-hydrocarbon hybrid surfactants in supercritical CO2.

PubMed

Sagisaka, Masanobu; Ono, Shinji; James, Craig; Yoshizawa, Atsushi; Mohamed, Azmi; Guittard, Frédéric; Enick, Robert M; Rogers, Sarah E; Czajka, Adam; Hill, Christopher; Eastoe, Julian

2018-08-01

Previous work (M. Sagisaka, et al. Langmuir 31 (2015) 7479-7487), showed the most effective fluorocarbon (FC) and hydrocarbon (HC) chain lengths in the hybrid surfactants FCm-HCn (sodium 1-oxo-1-[4-(perfluoroalkyl)phenyl]alkane-2-sulfonates, where m = FC length and n = HC length) were m and n = 6 and 4 for water solubilization, whereas m 6 and n 6, or m 6 and n 5, were optimal chain lengths for reversed micelle elongation in supercritical CO 2 . To clarify why this difference of only a few methylene chain units is so effective at tuning the solubilizing power and reversed micelle morphology, nanostructures of water-in-CO 2 (W/CO 2 ) microemulsions were investigated by high-pressure small-angle neutron scattering (SANS) measurements at different water-to-surfactant molar ratios (W 0 ) and surfactant concentrations. By modelling SANS profiles with cylindrical and ellipsoidal form factors, the FC6-HCn/W/CO 2 microemulsions were found to increase in size with increasing W 0 and surfactant concentration. Ellipsoidal cross-sectional radii of the FC6-HC4/W/CO 2 microemulsion droplets increased linearly with W 0 , and finally reached ∼39 Å and ∼78 Å at W 0  = 85 (close to the upper limit of solubilizing power). These systems appear to be the largest W/CO 2 microemulsion droplets ever reported. The aqueous domains of FC6-HC6 rod-like reversed micelles increased in size by 3.5 times on increasing surfactant concentration from 35 mM to 50 mM: at 35 mM, FC6-HC5 formed rod-like reversed micelles 5.3 times larger than FC6-HC6. Interestingly, these results suggest that hybrid HC-chains partition into the microemulsion aqueous cores with the sulfonate headgroups, or at the W/CO 2 interfaces, and so play important roles for tuning the W/CO 2 interfacial curvature. The super-efficient W/CO 2 -type solubilizer FC6-HC4, and the rod-like reversed micelle forming surfactant FC6-HC5, represent the most successful cases of low fluorine content additives. These surfactants facilitate VOC-free, effective and energy-saving CO 2 solvent systems for applications such as extraction, dyeing, dry cleaning, metal-plating, enhanced oil recovery and organic/inorganic or nanomaterial synthesis. Copyright © 2017 Elsevier B.V. All rights reserved.

Surfactant Behavior of Sodium Dodecylsulfate in Deep Eutectic Solvent Choline Chloride/Urea.

PubMed

Arnold, T; Jackson, A J; Sanchez-Fernandez, A; Magnone, D; Terry, A E; Edler, K J

2015-12-01

Deep eutectic solvents (DES) resemble ionic liquids but are formed from an ionic mixture instead of being a single ionic compound. Here we present some results that demonstrate that surfactant sodium dodecyl sulfate (SDS) remains surface-active and shows self-assembly phenomena in the most commonly studied DES, choline chloride/urea. X-ray reflectivity (XRR) and small angle neutron scattering (SANS) suggest that the behavior is significantly different from that in water. Our SANS data supports our determination of the critical micelle concentration using surface-tension measurements and suggests that the micelles formed in DES do not have the same shape and size as those seen in water. Reflectivity measurements have also demonstrated that the surfactants remain surface-active below this concentration.

Photophysical studies on curcumin-sophorolipid nanostructures: applications in quorum quenching and imaging

PubMed Central

2018-01-01

Sophorolipid biosurfactants are biodegradable, less toxic and FDA approved. The purified acidic form of sophorolipid is stimuli-responsive with self-assembling properties and used for solubilizing hydrophobic drugs. This study encapsulated curcumin (CU) with acidic sophorolipid (ASL) micelles and analysed using photophysical studies like UV-visible spectroscopy, photoluminescence (PL) spectroscopy and time-correlated single photon counting (TCSPC). TEM images have revealed ellipsoid micelles of approximately 100 nm size and were confirmed by dynamic light scattering. The bacterial fluorescence uptake studies showed the uptake of formed CUASL nanostructures into both Gram-positive and Gram-negative bacteria. They also showed quorum quenching activity against Pseudomonas aeruginosa. The results have demonstrated this system has potential theranostic applications. PMID:29515826

Reverse Micelle Based Synthesis of Microporous Materials in Microgravity

NASA Technical Reports Server (NTRS)

Dutta, Prabir K.

1995-01-01

Formation of zincophosphates from zinc and phosphate containing reverse micelles (water droplets in hexane) has been examined. The frameworks formed resemble that made by conventional hydrothermal synthesis. Dynamics of crystal growth are however quite different, and form the main focus of this study. In particular, the formation of zincophosphate with the sodalite framework was examined in detail. The intramicellar pH was found to have a strong influence on crystal growth. Crystals with a cubic morphology were formed directly from the micelles, without an apparent intermediate amorphous phase over a period of four days by a layer-bylayer growth at the intramicellar pH of 7.6. At a pH of 6.8, an amorphous precipitate rapidly sediments in hours. Sodalite was eventually formed from this settled phase via surface diffusion and reconstruction within four days. With a rotating cell, it was possible to minimize sedimentation and crystals were found to grow epitaxially from the spherical, amorphous particles. Intermediate pH's of 7.2 led to formation of aggregated sodalite crystals prior to settling, again without any indication of an intermediate amorphous phase. These diverse pathways were possible due to changes in intramicellar supersaturation conditions by minor changes in pH. In contrast, conventional syntheses in this pH range all proceeded by similar crystallization pathways through an amorphous gel. This study establishes that synthesis of microporous frameworks is not only possible in reverse micellar systems, but they also allow examination of possible crystallization pathways.

The emergence and evolution of life in a "fatty acid world" based on quantum mechanics.

PubMed

Tamulis, Arvydas; Grigalavicius, Mantas

2011-02-01

Quantum mechanical based electron correlation interactions among molecules are the source of the weak hydrogen and Van der Waals bonds that are critical to the self-assembly of artificial fatty acid micelles. Life on Earth or elsewhere could have emerged in the form of self-reproducing photoactive fatty acid micelles, which gradually evolved into nucleotide-containing micelles due to the enhanced ability of nucleotide-coupled sensitizer molecules to absorb visible light. Comparison of the calculated absorption spectra of micelles with and without nucleotides confirmed this idea and supports the idea of the emergence and evolution of nucleotides in minimal cells of a so-called Fatty Acid World. Furthermore, the nucleotide-caused wavelength shift and broadening of the absorption pattern potentially gives these molecules an additional valuable role, other than a purely genetic one in the early stages of the development of life. From the information theory point of view, the nucleotide sequences in such micelles carry positional information providing better electron transport along the nucleotide-sensitizer chain and, in addition, providing complimentary copies of that information for the next generation. Nucleotide sequences, which in the first period of evolution of fatty acid molecules were useful just for better absorbance of the light in the longer wavelength region, later in the PNA or RNA World, took on the role of genetic information storage.

Enhanced gene expression promoted by hybrid magnetic/cationic block copolymer micelles.

PubMed

Haladjova, E; Rangelov, S; Tsvetanov, Ch B; Posheva, V; Peycheva, E; Maximova, V; Momekova, D; Mountrichas, G; Pispas, S; Bakandritsos, A

2014-07-15

We report on novel gene delivery vector systems based on hybrid polymer-magnetic micelles. The hybrid micelles were prepared by codissolution of hydrophobically surface modified iron oxide and amphiphilic polystyrene-b-poly(quaternized 2-vinylpyridine) block copolymer (PS-b-P2QVP) in organic solvent. After extensive dialysis against water, micelles with positively charged hydrophilic corona of PQVP and hydrophobic PS core were prepared, in which magnetic nanoparticles were randomly distributed. The hybrid micelles were used to form complexes with linear (salmon sperm, 2000 bp, corresponding to M(w) of 1.32 × 10(6) Da) and plasmid (pEGFP-N1, 4730 bp, corresponding to M(w) of 3.12 × 10(6) Da) DNA. The resulting magnetopolyplexes of phosphate:amine (P/N) ratios in the 0.05-20 range were characterized by light scattering, ζ-potential measurements, and transmission electron microscopy as well as cytotoxicity and gel retardation assays. The investigated systems displayed a narrow size distribution, particle dimensions below 360 nm, whereas their ζ-potential values varied from positive to negative depending of the P/N ratio. The resulting vector nanosystems exhibited low toxicity. They were able to introduce pEGFP-N1 molecules into the cells. The application of a magnetic field markedly boosted the transgene expression efficiency of the magnetopolyplexes, which was even superior to those of commercial transfectants such as Lipofectamine and dendritic polyethylenimine.

Micelles as Delivery Vehicles for Oligofluorene for Bioimaging

PubMed Central

Su, Fengyu; Alam, Ruhaniyah; Mei, Qian; Tian, Yanqing; Meldrum, Deirdre R.

2011-01-01

With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG-NH2) to incorporate a hydrophobic blue emitter oligofluorene (OF) to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF). In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG) and esophagus premalignant (CP-A), were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields. PMID:21915324

Micelles as delivery vehicles for oligofluorene for bioimaging.

PubMed

Su, Fengyu; Alam, Ruhaniyah; Mei, Qian; Tian, Yanqing; Meldrum, Deirdre R

2011-01-01

With the successful development of organic/polymeric light emitting diodes, many organic and polymeric fluorophores with high quantum efficiencies and optical stability were synthesized. However, most of these materials which have excellent optical properties are insoluble in water, limiting their applications in biological fields. Herein, we used micelles formed from an amino-group-containing poly(ε-caprolactone)-block-poly(ethylene glycol) (PCL-b-PEG-NH(2)) to incorporate a hydrophobic blue emitter oligofluorene (OF) to enable its application in biological conditions. Although OF is completely insoluble in water, it was successfully transferred into aqueous solutions with a good retention of its photophysical properties. OF exhibited a high quantum efficiency of 0.84 in a typical organic solvent of tetrahydrofuran (THF). In addition, OF also showed a good quantum efficiency of 0.46 after being encapsulated into micelles. Two cells lines, human glioblastoma (U87MG) and esophagus premalignant (CP-A), were used to study the cellular internalization of the OF incorporated micelles. Results showed that the hydrophobic OF was located in the cytoplasm, which was confirmed by co-staining the cells with nucleic acid specific SYTO 9, lysosome specific LysoTracker Red®, and mitochondria specific MitoTracker Red. MTT assay indicated non-toxicity of the OF-incorporated micelles. This study will broaden the application of hydrophobic functional organic compounds, oligomers, and polymers with good optical properties to enable their applications in biological research fields.

Cylindrical micelles of a POSS amphiphilic dendrimer as nano-reactors for polymerization.

PubMed

Weng, Jing-Ting; Yeh, Tso-Fan; Samuel, Ashok Zachariah; Huang, Yi-Fan; Sie, Jyun-Hao; Wu, Kuan-Yi; Peng, Chi-How; Hamaguchi, Hiro-O; Wang, Chien-Lung

2018-02-15

A low generation amphiphilic dendrimer, POSS-AD, which has a POSS core and eight amphiphilic arms, was synthesized and used as a nano-reactor to produce well-defined polymer nano-cylinders. Confirmed by small-angle X-ray scattering (SAXS), Raman and NMR spectrometry, monodispersed cylindrical micelles that contain a hydrophilic cavity with a diameter of 2.09 nm and a length of 4.26 nm were produced via co-assembling POSS-AD with hydrophilic liquids, such as H 2 O and HEMA in hydrophobic solvents. Taking the HEMA/POSS-AD cylindrical micelles as nano-reactors, polymerization of HEMA within the micelles results in polymer nano-cylinders (POSS-ADNPs) with a diameter of 2.24 nm and a length of 5.02 nm. The study confirmed that despite the inability to maintain specific shape in solution, low generation dendrimers form well-defined nano-containers or nano-reactors, which relies on co-assembling with hydrophilic guest molecules. These nano-reactors are robust enough to maintain their shape during the polymerization of the guest molecules. Polymer nano-cylinders with dimensions less than 10 nm can thus be produced from the HEMA/POSS-AD micelles. Since the chemical structure of low-generation dendrimers and the contents of the co-assembled nano-reactors can be easily adjusted, the concept holds the potential for the further developments of low-generation amphiphilic dendrimers.

Quaternary complexes composed of plasmid DNA/protamine/fish sperm DNA/stearic acid grafted chitosan oligosaccharide micelles for gene delivery.

PubMed

Du, Yong-Zhong; Lu, Ping; Yuan, Hong; Zhou, Jian-Ping; Hu, Fu-Qiang

2011-01-01

Quaternary complexes with condensed core of plasmid DNA, protamine, fish sperm DNA and shell of stearic acid grafted chitosan oligosaccharide (CSO-SA), were prepared. The CSO-SA could self-assemble to form nano-sized micelles in aqueous solution and demonstrated excellent internalization ability of tumor cells. Dynamic light scattering (DLS) measurement and transmission electrostatic microscope (TEM) images showed that quaternary complexes had spherical shape with about 25 nm number average diameter, and the size of quaternary complexes was smaller than that of CSO-SA micelles and CSO-SA micelles/plasmid DNA binary complexes. The transfection efficiencies of quaternary complexes on HEK293 and MCF-7 cells increased with incubation time, and were significantly higher than that of CSO-SA micelles/plasmid DNA binary complexes. The optimal transfection efficiency of quaternary complexes on HEK293 and MCF-7 cells measured by flow cytometer after 96 h was 23.82% and 41.43%, respectively. Whereas, the transfection efficiency of Lipofectamine™ 2000 on HEK293 and MCF-7 cells after 96 h was 32.45% and 33.23%, respectively. The data of luciferease activity measurement showed that the optimal ratio of plasmid DNA:fish sperm DNA:protamine:CSO-SA was 1:1:5:5. The results indicated that the present quaternary complexes were potential non-viral gene delivery system. Copyright © 2010 Elsevier B.V. All rights reserved.

Effect of Hydrotropic Compounds on the Self-Organization and Solubilization Properties of Cationic Surfactants

NASA Astrophysics Data System (ADS)

Gaynanova, G. A.; Valeeva, F. G.; Kushnazarova, R. A.; Bekmukhametova, A. M.; Zakharov, S. V.; Mirgorodskaya, A. B.; Zakharova, L. Ya.

2018-07-01

The effect hydrotropic additives (salts of aromatic acids and choline chloride) have on the micelle-forming properties (the critical concentrations of micelle formation and the Krafft temperature) of cationic surfactants, and on the solubilization capability of mono- and dicationic surfactants toward such hydrophobic compounds as a Sudan I spectral probe and curcumin natural dye, is considered. The factors that govern solubilization capacity, e.g., the structure of the head group of surfactants, the nature of the solubilizate and hydrotropic additives, and the pH of the medium are determined.

The effect of micellization on the EPR spectra and reactivity of 2,2,4,4-tetramethylpiperidinoxyl (TEMPO) radicals.

PubMed

Aliaga, Carolina; Rezende, Marcos Caroli; Mena, Geraldine

2016-11-01

A series of 4-alkanoyloxy-2,2,6,6-tetramethylpiperidinoxyl radicals was prepared, and their reactivity in water vis-à-vis antioxidant Trolox was compared. Spectral (electron paramagnetic resonance) and dynamic-light-scattering measurements suggested the formation of micelles for the more hydrophobic members of the series. The observed increase in reactivity for the micelle-forming radicals reflected the increased local concentration of the radical fragment on the micellar interface. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Interfacial instability of wormlike micellar solutions sheared in a Taylor-Couette cell

NASA Astrophysics Data System (ADS)

Mohammadigoushki, Hadi; Muller, Susan J.

2014-10-01

We report experiments on wormlike micellar solutions sheared in a custom-made Taylor-Couette (TC) cell. The computer controlled TC cell allows us to rotate both cylinders independently. Wormlike micellar solutions containing water, CTAB, and NaNo3 with different compositions are highly elastic and exhibit shear banding within a range of shear rate. We visualized the flow field in the θ-z as well as r-z planes, using multiple cameras. When subject to low shear rates, the flow is stable and azimuthal, but becomes unstable above a certain threshold shear rate. This shear rate coincides with the onset of shear banding. Visualizing the θ-z plane shows that this instability is characterized by stationary bands equally spaced in the z direction. Increasing the shear rate results to larger wave lengths. Above a critical shear rate, experiments reveal a chaotic behavior reminiscent of elastic turbulence. We also studied the effect of ramp speed on the onset of instability and report an acceleration below which the critical Weissenberg number for onset of instability is unaffected. Moreover, visualizations in the r-z direction reveals that the interface between the two bands undulates. The shear band evolves towards the outer cylinder upon increasing the shear rate, regardless of which cylinder is rotating.

Neutral Polymer Micelle Carriers with pH-Responsive, Endosome-Releasing Activity Modulate Antigen Trafficking to Enhance CD8 T-Cell Responses

PubMed Central

Keller, Salka; Wilson, John T; Patilea, Gabriela I; Kern, Hanna B; Convertine, Anthony J; Stayton, Patrick S

2014-01-01

Synthetic subunit vaccines need to induce CD8+ cytotoxic T-cell (CTL) responses for effective vaccination against intracellular pathogens. Most subunit vaccines primarily generate humoral immune responses, with a weaker than desired CD8+ cytotoxic T-cell response. Here, a neutral, pH-responsive polymer micelle carrier that alters intracellular antigen trafficking was shown to enhance CD8+ T-cell responses with a correlated increase in cytosolic delivery and a decrease in exocytosis. Polymer diblock carriers consisted of a N-(2-hydroxypropyl) methacrylamide corona block with pendant pyridyl disulfide groups for reversible conjugation of thiolated ovalbumin, and a tercopolymer ampholytic core-forming block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The diblock copolymers self-assembled into 25–30 nm diameter micellar nanoparticles. Conjugation of ovalbumin to the micelles significantly enhanced antigen cross-presentation in vitro relative to free ovalbumin, an unconjugated physical mixture of ovalbumin and polymer, and a non pH-responsive micelle-ovalbumin control. Mechanistic studies in a murine dendritic cell line (DC2.4) demonstrated micelle-mediated enhancements in intracellular antigen retention and cytosolic antigen accumulation. Approximately 90% of initially internalized ovalbumin-conjugated micelles were retained in cells after 1.5 h, compared to only ~40% for controls. Furthermore, cells dosed with conjugates displayed 67-fold higher cytosolic antigen levels relative to soluble ovalbumin 4 h post uptake. Subcutaneous immunization of mice with ovalbumin-polymer conjugates significantly enhanced antigen-specific CD8+ T cell responses (0.4 % IFN-γ+ of CD8+) compared to immunization with soluble protein, ovalbumin and polymer mixture, and the control micelle without endosome-releasing activity. Additionally, pH-responsive carrier facilitated antigen delivery to antigen presenting cells in the draining lymph nodes. As early as 90 min post injection ova-micelle conjugates were associated with 28% and 55% of dendritic cells and macrophages, respectively. After 24 h, conjugates preferentially associated with dendritic cells, affording 30-, 3-, and 3-fold enhancements in uptake relative to free protein, physical mixture, and the non pH-responsive conjugate controls, respectively. These results demonstrate the potential of pH-responsive polymeric micelles for use in vaccine applications that rely on CD8+ T cell activation. PMID:24698946

Neutral polymer micelle carriers with pH-responsive, endosome-releasing activity modulate antigen trafficking to enhance CD8(+) T cell responses.

PubMed

Keller, Salka; Wilson, John T; Patilea, Gabriela I; Kern, Hanna B; Convertine, Anthony J; Stayton, Patrick S

2014-10-10

Synthetic subunit vaccines need to induce CD8(+) cytotoxic T cell (CTL) responses for effective vaccination against intracellular pathogens. Most subunit vaccines primarily generate humoral immune responses, with a weaker than desired CD8(+) cytotoxic T cell response. Here, a neutral, pH-responsive polymer micelle carrier that alters intracellular antigen trafficking was shown to enhance CD8(+) T cell responses with a correlated increase in cytosolic delivery and a decrease in exocytosis. Polymer diblock carriers consisted of a N-(2-hydroxypropyl) methacrylamide corona block with pendent pyridyl disulfide groups for reversible conjugation of thiolated ovalbumin, and a tercopolymer ampholytic core-forming block composed of propylacrylic acid (PAA), dimethylaminoethyl methacrylate (DMAEMA), and butyl methacrylate (BMA). The diblock copolymers self-assembled into 25-30nm diameter micellar nanoparticles. Conjugation of ovalbumin to the micelles significantly enhanced antigen cross-presentation in vitro relative to free ovalbumin, an unconjugated physical mixture of ovalbumin and polymer, and a non-pH-responsive micelle-ovalbumin control. Mechanistic studies in a murine dendritic cell line (DC 2.4) demonstrated micelle-mediated enhancements in intracellular antigen retention and cytosolic antigen accumulation. Approximately 90% of initially internalized ovalbumin-conjugated micelles were retained in cells after 1.5h, compared to only ~40% for controls. Furthermore, cells dosed with conjugates displayed 67-fold higher cytosolic antigen levels relative to soluble ovalbumin 4h post uptake. Subcutaneous immunization of mice with ovalbumin-polymer conjugates significantly enhanced antigen-specific CD8(+) T cell responses (0.4% IFN-γ(+) of CD8(+)) compared to immunization with soluble protein, ovalbumin and polymer mixture, and the control micelle without endosome-releasing activity. Additionally, pH-responsive carrier facilitated antigen delivery to antigen presenting cells in the draining lymph nodes. As early as 90min post injection, ova-micelle conjugates were associated with 28% and 55% of dendritic cells and macrophages, respectively. After 24h, conjugates preferentially associated with dendritic cells, affording 30-, 3-, and 3-fold enhancements in uptake relative to free protein, physical mixture, and the non-pH-responsive conjugate controls, respectively. These results demonstrate the potential of pH-responsive polymeric micelles for use in vaccine applications that rely on CD8(+) T cell activation. Copyright © 2014 Elsevier B.V. All rights reserved.

Importance of casein micelle size and milk composition for milk gelation.

PubMed

Glantz, M; Devold, T G; Vegarud, G E; Lindmark Månsson, H; Stålhammar, H; Paulsson, M

2010-04-01

The economic output of the dairy industry is to a great extent dependent on the processing of milk into other milk-based products such as cheese. The yield and quality of cheese are dependent on both the composition and technological properties of milk. The objective of this study was to evaluate the importance and effects of casein (CN) micelle size and milk composition on milk gelation characteristics in order to evaluate the possibilities for enhancing gelation properties through breeding. Milk was collected on 4 sampling occasions at the farm level in winter and summer from dairy cows with high genetic merit, classified as elite dairy cows, of the Swedish Red and Swedish Holstein breeds. Comparisons were made with milk from a Swedish Red herd, a Swedish Holstein herd, and a Swedish dairy processor. Properties of CN micelles, such as their native and rennet-induced CN micelle size and their zeta-potential, were analyzed by photon correlation spectroscopy, and rennet-induced gelation characteristics, including gel strength, gelation time, and frequency sweeps, were determined. Milk parameters of the protein, lipid, and carbohydrate profiles as well as minerals were used to obtain correlations with native CN micelle size and gelation characteristics. Milk pH and protein, CN, and lactose contents were found to affect milk gelation. Smaller native CN micelles were shown to form stronger gels when poorly coagulating milk was excluded from the correlation analysis. In addition, milk pH correlated positively, whereas Mg and K correlated negatively with native CN micellar size. The milk from the elite dairy cows was shown to have good gelation characteristics. Furthermore, genetic progress in relation to CN micelle size was found for these cows as a correlated response to selection for the Swedish breeding objective if optimizing for milk gelation characteristics. The results indicate that selection for smaller native CN micelles and lower milk pH through breeding would enhance gelation properties and may thus improve the initial step in the processing of cheese. Copyright (c) 2010 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Investigation of laundering and dispersion approaches for silica and calcium phosphosilicate composite nanoparticles synthesized in reverse micelles

NASA Astrophysics Data System (ADS)

Tabakovic, Amra

Nanotechnology, the science and engineering of materials at the nanoscale, is a booming research area with numerous applications in electronic, cosmetic, automotive and sporting goods industries, as well as in biomedicine. Composite nanoparticles (NPs) are of special interest since the use of two or more materials in NP design imparts multifunctionality on the final NP constructs. This is especially relevant for applications in areas of human healthcare, where the use of dye or drug doped composite NPs is expected to improve the diagnosis and treatment of cancer and other serious illnesses. Since the physicochemical properties of NP suspensions dictate the success of these systems in biomedical applications, especially drug delivery of chemotherapeutics, synthetic routes which offer precise control of NP properties, especially particle diameter and colloidal stability, are utilized to form a variety of composite NPs. Formation of NPs in reverse, or water-in-oil, micelles is one such synthetic approach. However, while the use of reverse micelles to form composite NPs offers precise control over NP size and shape, the post-synthesis laundering and dispersion of synthesized NP suspensions can still be a challenge. Reverse micelle synthetic approaches require the use of surfactants and low dielectric constant solvents, like hexane and cyclohexane, as the oil phase, which can compromise the biocompatibility and colloidal stability of the final composite NP suspensions. Therefore, appropriate dispersants and solvents must be used during laundering and dispersion to remove surfactant and ensure stability of synthesized NPs. In the work presented in this dissertation, two laundering and dispersion approaches, including packed column high performance liquid chromatography (HPLC) and centrifugation (sedimentation and redispersion), are investigated for silver core silica (Ag-SiO2) and calcium phosphosilicate (Caw(HxPO4)y(Si(OH)zOa) b · cH2O, CPS) composite NP suspensions synthesized in a cyclohexane/ polyoxyethylene (5) nonylphenylether (IgepalRTM CO-520) /water reverse micelle system.

Binding of vitamin A by casein micelles in commercial skim milk.

PubMed

Mohan, M S; Jurat-Fuentes, J L; Harte, F

2013-02-01

Recent studies have shown that reassembled micelles formed by caseinates and purified casein fractions (α(s)- and β-casein) bind to hydrophobic compounds, including curcumin, docosahexaenoic acid, and vitamin D. However, limited research has been done on the binding of hydrophobic compounds by unmodified casein micelles in skim milk. In the present study, we investigated the ability of casein micelles in commercial skim milk to associate with vitamin A (retinyl palmitate), a fat-soluble vitamin commonly used to fortify milk. Milk protein fractions from different commercially available skim milk samples subjected to different processing treatments, including pasteurized, ultrapasteurized, organic pasteurized, and organic ultrapasteurized milks, were separated by fast protein liquid chromatography. The fractions within each peak were combined and freeze-dried. Sodium dodecyl sulfate-PAGE with silver staining was used to identify the proteins present in each of the fractions. The skim milk samples and fractions were extracted for retinyl palmitate and quantified against a standard using normal phase-HPLC. Retinyl palmitate was found to associate with the fraction of skim milk containing caseins, whereas the other proteins (BSA, β-lactoglobulin, α-lactalbumin) did not show any binding. The retinyl palmitate content in the various samples ranged from 1.59 to 2.48 µg of retinyl palmitate per mL of milk. The casein fractions contained between 14 and 40% of total retinyl palmitate in the various milks tested. The variation in the retention of vitamin A by caseins was probably explained by differences in the processing of different milk samples, including thermal treatment, the form of vitamin A emulsion used for fortification, and the point of fortification during processing. Unmodified casein micelles have a strong intrinsic affinity toward the binding of vitamin A used to fortify commercially available skim milks. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Simulation of the shape and size of casein micelles in a film state.

PubMed

Gebhardt, Ronald; Kulozik, Ulrich

2014-04-01

Size fractionated casein micelles (CMs) form homogeneous films in which they are densely packed. The lateral size of CMs in films can be well resolved by surface-sensitive methods, but the estimation of their heights is still a challenge. We show that height information can be obtained from scattering patterns of GISAXS experiments on highly ordered casein films. We use an elastic scattering approach within the distorted wave Born approximation (DWBA) to simulate for the first time the two-dimensional intensity distribution of a GISAXS experiment of the CM near their critical angle. The model which fits the GISAXS data best considers an ellipsoidal form factor for the CM and an arrangement on a hexagonal lattice. Our results indicate that during film formation the spherical solution structure of CMs becomes compressed in the direction perpendicular to the film surface. In the film state, the micelles assume an oblate ellipsoidal shape with an aspect ratio of 1.9. Hence, their surface and contact area to the surrounding increases. As a result, the density of κ-casein on the micellar surface decreases, which could influence the functional properties of coatings and films.

Coacervates of lactotransferrin and β- or κ-casein: structure determined using SAXS.

PubMed

de Kruif, C G Kees; Pedersen, JanSkov; Huppertz, Thom; Anema, Skelte G

2013-08-20

Lactotransferrin (LF) is a large globular protein in milk with immune-regulatory and bactericidal properties. At pH 6.5, LF (M = 78 kDa) carries a net (calculated) charge of +21. β-Casein (BCN) and κ-casein (KCN) are part of the casein micelle complex in milk. Both BCN and KCN are amphiphillic proteins with a molar mass of 24 and 19 kDa and carry net charges of -14 and -4, respectively. Both BCN and KCN form soap-like micelles, with 40 and 65 monomers, respectively. The net negative charges are located in the corona of the micelles. On mixing LF with the caseins, coacervates are formed. We analyzed the structure of these coarcervates using SAXS. It was found that LF binds to the corona of the micellar structures, at the charge neutrality point. BCN/LF and KCN/LF ratios at the charge neutrality point were found to be ~1.2 and ~5, respectively. We think that the findings are relevant for the protection mechanism of globular proteins in bodily fluids where unstructured proteins are abundant (saliva). The complexes will prevent docking of enzymes on specific charged groups on the globular protein.

Impact of cationic surfactant on the self-assembly of sodium caseinate.

PubMed

Vinceković, Marko; Curlin, Marija; Jurašin, Darija

2014-08-27

The impact of a cationic surfactant, dodecylammonium chloride (DDACl), on the self-assembly of sodium caseinate (SC) has been investigated by light scattering, zeta potential, and rheological measurements as well as by microscopy (transmission electron and confocal laser scanning microscopy). In SC dilute solutions concentration-dependent self-assembly proceeds through the formation of spherical associates and their aggregation into elongated structures composed of connected spheres. DDACl interacts with SC via its hydrophilic and hydrophobic groups, inducing changes in SC self-assembled structures. These changes strongly depend on the surfactant aggregation states (monomeric or micellar) as well as concentration ratio of both components, leading to the formation of soluble and insoluble complexes of nano- to microdimensions. DDACl monomers interact with SC self-assembled entities in a different way compared to their micelles. Surfactant monomers form soluble complexes (similar to surfactant mixed micelles) at lower SC concentration but insoluble gelatinous complexes at higher SC concentration. At surfactant micellar concentration soluble complexes with casein chains wrapped around surfactant micelles are formed. This study suggests that the use of proper cationic surfactant concentration will allow modification and control of structural changes of SC self-assembled entities.

Small angle x ray scattering studies of reverse micelles in supercritical fluids

NASA Astrophysics Data System (ADS)

Pfund, D. M.; Fulton, J. L.

1994-10-01

The nature of aggregates formed in a supercritical fluid determines its solvent power and selectivity. Small angle X ray scattering (SAXS) is a powerful tool for studying the properties of aggregates with sizes in the 10(angstrom) to 200(angstrom) range. It is also useful in studying those interparticle interactions which operate over a similar distance. The authors have used SAXS to examine the aggregates formed in pure fluids, in mixtures and in fluid/surfactant/water systems. The scattered intensity as a function of angle depends on the geometry, polydispersity, X ray contrast, and interaction strength of the particles as well as on the phase behavior of the system. In this paper the authors present the results of modeling the X-ray scattering from AOT/water reverse micelles in supercritical propane and in propane/carbon dioxide mixtures. They examine the effect of dilution with CO2 anti-solvent on the phase behavior of the system and on the strength of intermicellar attractions. A better understanding of these systems must be obtained before the applications of supercritical reverse micelle systems to extractions, reactions, and enhanced oil recovery can be fully developed.

Histopathological and biochemical changes following fat embolism with administration of corn oil micelles: a new animal model for fat embolism syndrome.

PubMed

Liu, D D; Hsieh, N-K; Chen, H I

2008-11-01

Several experimental models have been used to produce intravascular fat embolism. We have developed a simple technique to induce fat embolism using corn oil emulsified with distilled water to form fatty micelles. Fat embolism was produced by intravenous administration of these fatty micelles in anaesthetised rats, causing alveolar oedema, haemorrhage and increased lung weight. Histopathological examination revealed fatty droplets and fibrin thrombi in the lung, kidney and brain. The arteriolar lumen was filled with fatty deposits. Following fat embolism, hypoxia and hypercapnia occurred. The plasma phospholipase A(2), nitrate/nitrite, methylguidanidine and proinflammatory cytokines were significantly increased. Mass spectrometry showed that the main ingredient of corn oil was oleic acid. This simple technique may be applied as a new animal model for the investigation of the mechanisms involved in the fat embolism syndrome.

A novel system for water soluble protein encapsulation with high efficiency: "micelles enhanced" polyelectrolyte capsules.

PubMed

Li, Xiaodong; Li, Xiaohui; Zhang, Jianxiang; Zhao, Shifang; Shen, Jiacong

2008-06-01

Novel "micelles enhanced" polyelectrolyte (PE) capsules based on functional templates of hybrid calcium carbonate were fabricated. Evidences suggested that the structure of capsule wall was different from that of conventional PE capsules, and the wall permeability of these PE capsules changed significantly. Lysozyme, a positively charged protein in neutral solution, was studied as a model protein to be encapsulated into the "micelles enhanced" PE capsules. Confocal laser scanning microscope was used to observe the entrapping process in real time, while UV-Vis spectroscope and scanning force microscope measurements suggested the high efficiency of encapsulation. In addition, the fluorescence recovery after photobleaching technique was employed to determine the existence form of deposited molecules. Further studies showed even negatively charged water-soluble peptides or proteins can be encapsulated into these hybrid capsules by modulating the pH value in bulk solution under its isoelectronic point as well. Copyright 2007 Wiley Periodicals, Inc.

Tailored hierarchical micelle architectures using living crystallization-driven self-assembly in two dimensions

NASA Astrophysics Data System (ADS)

Hudson, Zachary M.; Boott, Charlotte E.; Robinson, Matthew E.; Rupar, Paul A.; Winnik, Mitchell A.; Manners, Ian

2014-10-01

Recent advances in the self-assembly of block copolymers have enabled the precise fabrication of hierarchical nanostructures using low-cost solution-phase protocols. However, the preparation of well-defined and complex planar nanostructures in which the size is controlled in two dimensions (2D) has remained a challenge. Using a series of platelet-forming block copolymers, we have demonstrated through quantitative experiments that the living crystallization-driven self-assembly (CDSA) approach can be extended to growth in 2D. We used 2D CDSA to prepare uniform lenticular platelet micelles of controlled size and to construct precisely concentric lenticular micelles composed of spatially distinct functional regions, as well as complex structures analogous to nanoscale single- and double-headed arrows and spears. These methods represent a route to hierarchical nanostructures that can be tailored in 2D, with potential applications as diverse as liquid crystals, diagnostic technology and composite reinforcement.

Doxorubicin-loaded aromatic imine-contained amphiphilic branched star polymer micelles: synthesis, self-assembly, and drug delivery

PubMed Central

Qiu, Liang; Hong, Chun-Yan; Pan, Cai-Yuan

2015-01-01

Redox-and pH-sensitive branched star polymers (BSPs), BP(DMAEMA-co-MAEBA-co-DTDMA)(PMAIGP)ns, have been successively prepared by two steps of reversible addition–fragmentation chain transfer (RAFT) polymerization. The first step is RAFT polymerization of 2-(N,N-dimethylaminoethyl)methacrylate (DMAEMA) and p-(methacryloxyethoxy) benzaldehyde (MAEBA) in the presence of divinyl monomer, 2,2′-dithiodiethoxyl dimethacrylate (DTDMA). The resultant branched polymers were used as a macro-RAFT agent in the subsequent RAFT polymerization. After hydrolysis of the BSPs to form BP(DMAEMA-co-MAEBA-co-DTDMA)(PMAGP)ns (BSP-H), the anticancer drug doxorubicin (DOX) was covalently linked to branched polymer chains by reaction of primary amine of DOX and aldehyde groups in the polymer chains. Their compositions, structures, molecular weights, and molecular weight distributions were respectively characterized by nuclear magnetic resonance spectra and gel permeation chromatography measurements. The DOX-loaded micelles were fabricated by self-assembly of DOX-containing BSPs in water, which were characterized by transmission electron microscopy and dynamic light scattering. Aromatic imine linkage is stable in neutral water, but is acid-labile; controlled release of DOX from the BSP-H-DOX micelles was realized at pH values of 5 and 6, and at higher acidic solution, fast release of DOX was observed. In vitro cytotoxicity experiment results revealed low cytotoxicity of the BSPs and release of DOX from micelles in HepG2 and HeLa cells. Confocal laser fluorescence microscopy observations showed that DOX-loaded micelles have specific interaction with HepG2 cells. Thus, this type of BSP micelle is an efficient drug delivery system. PMID:26056444

Dynamics of micelle formation from temperature-jump Monte Carlo simulations.

PubMed

Heinzelmann, G; Seide, P; Figueiredo, W

2015-11-01

In the present work we perform temperature jumps in a surfactant solution by means of Monte Carlo simulations, investigating the dynamics of micelle formation. We use a lattice model that allows orientational freedom and hydrogen bonding for solvent molecules, which can make a connection between the different time scales of hydrogen bond formation and amphiphilic aggregation. When we perform a large jump between a high-temperature nonmicellized state and a micellized state, there is strong hysteresis between the heating and cooling processes, the latter showing the formation of premicelles that act as nucleation centers for the assembly of larger aggregates and the former is a drive for dissociation of the existing aggregates. Hysteresis is not seen when we perform a small jump between two states that can be both micellized or nonmicellized. Looking for a more detailed analysis of the hydrophobic effect that drives aggregation, we compare the time evolution of the solvent hydrogen bonds in our system close and far from micelles and how that is affected by the formation of large clusters at low temperatures. We find a strong connection between them, with the total number of hydrogen bonds in the system always increasing when micelles are formed. To gain insights into the mechanism of premicellar formation and growth, we measure the lifetime of micellized amphiphiles as a function of the aggregate size and the stage of the aggregation process. Our results indicate that the premicelles are always unstable, quickly exchanging amphiphiles with the solution due to their low probabilty in equilibrium. Furthermore, we find that the stability of individual surfactants in micelles increases with the aggregate size, with the lifetime of amphiphiles in large micelles being as much as 35 times longer than in the case of the unstable premicellar region.

NMR structure of the Arctic mutation of the Alzheimer's Aβ(1-40) peptide docked to SDS micelles

NASA Astrophysics Data System (ADS)

Usachev, K. S.; Filippov, A. V.; Khairutdinov, B. I.; Antzutkin, O. N.; Klochkov, V. V.

2014-11-01

The “Arctic” point mutation of the Alzheimer's amyloid β-peptide is a rare mutation leading to an early onset of Alzheimer's disease. The peptide may interact with neuronal membranes, where it can provide its toxic effects. We used 2D NMR spectroscopy to investigate the conformation of the “Arctic” mutant of Aβ1-40 Alzheimer's amyloid peptide in sodium dodecyl sulfate micelle solutions, which are the type of amphiphilic structures mimicking some properties of biomembranes. The study showed that the Arctic mutant of Aβ1-40 interacts with the surface of SDS micelles mainly through the Leu17-Asn27 310-helical region, while the Ile31-Val40 region is buried in the hydrophobic interior of the micelle. In contrast, wild-type Aβ1-40 interacts with SDS micelles through the Lys16-Asp23 α-helical region and Gly29-Met35. Both the Arctic mutant and the wild-type Aβ1-40 peptides interactions with SDS micelles are hydrophobic in nature. Aβ peptides are thought to be capable of forming pores in biomembranes that can cause changes in neuronal and endothelial cell membrane permeability. It has also been shown that Aβ peptides containing the “Arctic” mutation are more neurotoxic and aggregate more readily than the wild-type Aβ peptides at physiological conditions. Here, we propose that the extension of the helical structure of Leu17-Asn27 and a high aliphaticity (neutrality) of the C-terminal region in the Arctic Aβ peptides are consistent with the idea that formation of ion-permeable pores by Aβ oligomers may be one of prevailing mechanisms of a larger neuronal toxicity of the Arctic Aβ compared to the wild-type Aβ peptides, independent of oxidative damage and lipid peroxidation.

IR spectroscopy analysis of pancreatic lipase-related protein 2 interaction with phospholipids: 1. Discriminative recognition of mixed micelles versus liposomes.

PubMed

Mateos-Diaz, Eduardo; Bakala N'Goma, Jean-Claude; Byrne, Deborah; Robert, Sylvie; Carrière, Frédéric; Gaussier, Hélène

2018-03-01

Guinea pig pancreatic lipase-related protein 2 (GPLRP2) is an interesting model enzyme that can hydrolyze a large set of acylglycerols in vitro but displays however some selectivity depending on the supramolecular structure of substrate and the presence of surfactants like bile salts. We showed that GPLRP2 hydrolyzes 1,2-dipalmitoyl phosphatidylcholine (DPPC) present in mixed micelles with sodium taurodeoxycholate (NaTDC) but not in multilamellar (MLV) and large unilamellar (LUV) vesicles of DPPC. After characterization of these lipid aggregates by dynamic light scattering (DLS), the discriminative recognition of DPPC in DPPC/NaTDC micelles versus MLV and LUV by an inactive variant (S152G) of GPLRP2 to avoid the effect of substrate hydrolysis was investigated using Fourier transform infrared spectroscopy (FTIR). IR spectra were recorded after hydrogen/deuterium exchange, at pD 6 and various temperatures to study phase transitions. We analyzed the methylene asymmetric stretching (ν(CH2) as ), the carbonyl stretching (ν(CO)) and the composite polar head-group vibration bands, first to characterized differences in DPPC micelles and vesicles, and second to estimate the degree of interaction of GPLRP2 S152G with phospholipid. Our results indicate that a significant interaction between GPLRP2 S152G and DPPC is only observed when NaTDC is added to the system to form micelles and this can be explained by the different organization of DPPC in mixed micelles compared to lamellar vesicles (higher hydration of polar head, higher mobility of alkyl chains) that favors GPLRP2 penetration into the phospholipid layer. Copyright © 2017 Elsevier B.V. All rights reserved.

Kinetics of bacterial phospholipase C activity at micellar interfaces: effect of substrate aggregate microstructure and a model for the kinetic parameters.

PubMed

Singh, Jasmeet; Ranganathan, Radha; Hajdu, Joseph

2008-12-25

Activity at micellar interfaces of bacterial phospholipase C from Bacillus cereus on phospholipids solubilized in micelles was investigated with the goal of elucidating the role of the interface microstructure and developing further an existing kinetic model. Enzyme kinetics and physicochemical characterization of model substrate aggregates were combined, thus enabling the interpretation of kinetics in the context of the interface. Substrates were diacylphosphatidylcholine of different acyl chain lengths in the form of mixed micelles with dodecyldimethylammoniopropanesulfonate. An early kinetic model, reformulated to reflect the interfacial nature of the kinetics, was applied to the kinetic data. A better method of data treatment is proposed, use of which makes the presence of microstructure effects quite transparent. Models for enzyme-micelle binding and enzyme-lipid binding are developed, and expressions incorporating the microstructural properties are derived for the enzyme-micelle dissociation constant K(s) and the interface Michaelis-Menten constant, K(M). Use of these expressions in the interface kinetic model brings excellent agreement between the kinetic data and the model. Numerical values for the thermodynamic and kinetic parameters are determined. Enzyme-lipid binding is found to be an activated process with an acyl chain length dependent free energy of activation that decreases with micelle lipid molar fraction with a coefficient of about -15RT and correlates with the tightness of molecular packing in the substrate aggregate. Thus, the physical insight obtained includes a model for the kinetic parameters that shows that these parameters depend on the substrate concentration and acyl chain length of the lipid. Enzyme-micelle binding is indicated to be hydrophobic and solvent mediated with a dissociation constant of 1.2 mM.

Modelling the dynamics of a minimal protocell container

NASA Astrophysics Data System (ADS)

Nilsson Jacobi, Martin; Rasmussen, Steen; Tunstrøm, Kolbjørn

2005-01-01

This paper is a discussion on how reaction kinetics and three-dimensional (3D) lattice simulations can be used to elucidate the dynamical properties of micelles as a possible minimal protocell container. We start with a general discussion on the role of molecular self-assembly in prebiotic and contemporary biological systems. A simple reaction kinetic model of a micellation process of amphiphilic molecules in water is then presented and solved analytically. Amphiphilic molecules are polymers with hydrophobic (water-fearing), e.g. hydrocarbon tail groups, and hydrophilic (water-loving) head groups, e.g. fatty acids. By making a few simplifying assumptions an analytical expression for the size distribution of the resulting micelles can be derived. The main part of the paper presents and discusses a lattice gas technique for a more detailed 3D simulation of molecular self-assembly of amphiphilic polymers in aqueous environments. Water molecules, hydrocarbon tail groups and hydrophilic head groups are explicitly represented on a three-dimensional discrete lattice. Molecules move on the lattice proportional to their continuous momentum. Collision rules preserve momentum and kinetic energy. Potential energy from molecular interactions are also included explicitly. The non-trivial thermodynamics of large-scale and long-time dynamics are studied. In this paper we specifically demonstrate how, from a random initial distribution, micelles are formed and grow until they destabilize and can divide. Eventually a steady state of growing and dividing micelles is formed. Towards the end of the paper we discuss the relevance of the presented results to the design of a minimal artificial protocell.

Truxene-Based Hyperbranched Conjugated Polymers: Fluorescent Micelles Detect Explosives in Water.

PubMed

Huang, Wei; Smarsly, Emanuel; Han, Jinsong; Bender, Markus; Seehafer, Kai; Wacker, Irene; Schröder, Rasmus R; Bunz, Uwe H F

2017-01-25

We report two hyperbranched conjugated polymers (HCP) with truxene units as core and 1,4-didodecyl-2,5-diethynylbenzene as well as 1,4-bis(dodecyloxy)-2,5-diethynylbenzene as comonomers. Two analogous poly(para-phenyleneethynylene)s (PPE) are also prepared as comparison to demonstrate the difference between the truxene and the phenyl moieties in their optical properties and their sensing performance. The four polymers are tested for nitroaromatic analytes and display different fluorescence quenching responses. The quenching efficiencies are dependent upon the spectral overlap between the absorbance of the analyte and the emission of the fluorescent polymer. Optical fingerprints are obtained, based on the unique response patterns of the analytes toward the polymers. With this small sensor array, one can distinguish nine nitroaromatic analytes with 100% accuracy. The amphiphilic polymer F127 (a polyethylene glycol-polypropylene glycol block copolymer) carries the hydrophobic HCPs and self-assembles into micelles in water, forming highly fluorescent HCP micelles. The micelle-bound conjugated polymers detect nitroaromatic analytes effectively in water and show an increased sensitivity compared to the sensing of nitroaromatics in organic solvents. The nitroarenes are also discriminated in water using this four-element chemical tongue.

Selective Antimicrobial Activities and Action Mechanism of Micelles Self-Assembled by Cationic Oligomeric Surfactants.

PubMed

Zhou, Chengcheng; Wang, Fengyan; Chen, Hui; Li, Meng; Qiao, Fulin; Liu, Zhang; Hou, Yanbo; Wu, Chunxian; Fan, Yaxun; Liu, Libing; Wang, Shu; Wang, Yilin

2016-02-17

This work reports that cationic micelles formed by cationic trimeric, tetrameric, and hexameric surfactants bearing amide moieties in spacers can efficiently kill Gram-negative E. coli with a very low minimum inhibitory concentration (1.70-0.93 μM), and do not cause obvious toxicity to mammalian cells at the concentrations used. With the increase of the oligomerization degree, the antibacterial activity of the oligomeric surfactants increases, i.e., hexameric surfactant > tetrameric surfactant > trimeric surfactant. Isothermal titration microcalorimetry, scanning electron microscopy, and zeta potential results reveal that the cationic micelles interact with the cell membrane of E. coli through two processes. First, the integrity of outer membrane of E. coli is disrupted by the electrostatic interaction of the cationic ammonium groups of the surfactants with anionic groups of E. coli, resulting in loss of the barrier function of the outer membrane. The inner membrane then is disintegrated by the hydrophobic interaction of the surfactant hydrocarbon chains with the hydrophobic domains of the inner membrane, leading to the cytoplast leakage. The formation of micelles of these cationic oligomeric surfactants at very low concentration enables more efficient interaction with bacterial cell membrane, which endows the oligomeric surfactants with high antibacterial activity.

Enhancing fluorescence intensity of Ellagic acid in Borax-HCl-CTAB micelles

NASA Astrophysics Data System (ADS)

Wang, Feng; Huang, Wei; Zhang, Shuai; Liu, Guokui; Li, Kexiang; Tang, Bo

2011-03-01

Ellagic acid (C 14H 6O 8), a naturally occurring phytochemical, found mainly in berries and some nuts, has anticarcinogenic and antioxidant properties. It is found that fluorescence of Ellagic acid (EA) is greatly enhanced by micelle of cetyltrimethylammonium bromide (CTAB) surfactant. Based on this effect, a sensitive proposed fluorimetric method was applied for the determination of Ellagic acid in aqueous solution. In the Borax-HCl buffer, the fluorescence intensity of Ellagic acid in the presence of CTAB is proportional to the concentration of Ellagic acid in range from 8.0 × 10 -10 to 4.0 × 10 -5 mol L -1; and the detection limits are 3.2 × 10 -10 mol L -1 and 5.9 × 10 -10 mol L -1 excited at 266 nm and 388 nm, respectively. The actual samples of pomegranate rinds are simply manipulated and satisfactorily determined. The interaction mechanism studies argue that the negative EA-Borax complex is formed and solubilized in the cationic surfactant CTAB micelle in this system. The fluorescence intensity of EA enhances because the CTAB micelle provides a hydrophobic microenvironment for EA-Borax complex, which can prevent collision with water molecules and decrease the energy loss of EA-Borax complex.

From carbon nanotubes to carbon atomic chains

NASA Astrophysics Data System (ADS)

Casillas García, Gilberto; Zhang, Weijia; José-Yacamán, Miguel

2010-10-01

Carbyne is a linear allotrope of carbon. It is formed by a linear arrangement of carbon atoms with sp-hybridization. We present a reliable and reproducible experiment to obtain these carbon atomic chains using few-layer-graphene (FLG) sheets and a HRTEM. First the FLG sheets were synthesized from worm-like exfoliated graphite and then drop-casted on a lacey-carbon copper grid. Once in the TEM, two holes are opened near each other in a FLG sheet by focusing the electron beam into a small spot. Due to the radiation, the carbon atoms rearrange themselves between the two holes and form carbon fibers. The beam is concentrated on the carbon fibers in order excite the atoms and induce a tension until multi wall carbon nanotube (MWCNT) is formed. As the radiation continues the MWCNT breaks down until there is only a single wall carbon nanotube (SWCNT). Then, when the SWCNT breaks, an atomic carbon chain is formed, lasts for several seconds under the radiation and finally breaks. This demonstrates the stability of this carbon structure.

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

PubMed Central

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

2015-01-01

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. The fluorescence quenching experiments of SEs at the palisade of Triton X-100 micelles indicate a blocking effect dependent on the number of methylene units present in the hydrophobic tail of the surfactant. A remarkable blocking effect is observed when there is a match in size between the hydrophobic regions forming the apolar core (lauryl SE/ Triton X-100). This blocking effect disappears when a mismatch in size between hydrophobic tails, exists due to the disturbing effect on the micelle core. PMID:25905632

Folding Behaviors of Protein (Lysozyme) Confined in Polyelectrolyte Complex Micelle.

PubMed

Wu, Fu-Gen; Jiang, Yao-Wen; Chen, Zhan; Yu, Zhi-Wu

2016-04-19

The folding/unfolding behavior of proteins (enzymes) in confined space is important for their properties and functions, but such a behavior remains largely unexplored. In this article, we reported our finding that lysozyme and a double hydrophilic block copolymer, methoxypoly(ethylene glycol)5K-block-poly(l-aspartic acid sodium salt)10 (mPEG(5K)-b-PLD10), can form a polyelectrolyte complex micelle with a particle size of ∼30 nm, as verified by dynamic light scattering and transmission electron microscopy. The unfolding and refolding behaviors of lysozyme molecules in the presence of the copolymer were studied by microcalorimetry and circular dichroism spectroscopy. Upon complex formation with mPEG(5K)-b-PLD10, lysozyme changed from its initial native state to a new partially unfolded state. Compared with its native state, this copolymer-complexed new folding state of lysozyme has different secondary and tertiary structures, a decreased thermostability, and significantly altered unfolding/refolding behaviors. It was found that the native lysozyme exhibited reversible unfolding and refolding upon heating and subsequent cooling, while lysozyme in the new folding state (complexed with the oppositely charged PLD segments of the polymer) could unfold upon heating but could not refold upon subsequent cooling. By employing the heating-cooling-reheating procedure, the prevention of complex formation between lysozyme and polymer due to the salt screening effect was observed, and the resulting uncomplexed lysozyme regained its proper unfolding and refolding abilities upon heating and subsequent cooling. Besides, we also pointed out the important role the length of the PLD segment played during the formation of micelles and the monodispersity of the formed micelles. Furthermore, the lysozyme-mPEG(5K)-b-PLD10 mixtures prepared in this work were all transparent, without the formation of large aggregates or precipitates in solution as frequently observed in other protein-polyelectrolyte systems. Hence, the present protein-PEGylated poly(amino acid) mixture provides an ideal water-soluble model system to study the important role of electrostatic interaction in the complexation between proteins and polymers, leading to important new knowledge on the protein-polymer interactions. Moreover, the polyelectrolyte complex micelle formed between protein and PEGylated polymer may provide a good drug delivery vehicle for therapeutic proteins.

Stepwise-activable multifunctional peptide-guided prodrug micelles for cancerous cells intracellular drug release

NASA Astrophysics Data System (ADS)

Zhang, Jing; Li, Mengfei; Yuan, Zhefan; Wu, Dan; Chen, Jia-da; Feng, Jie

2016-10-01

A novel type of stepwise-activable multifunctional peptide-guided prodrug micelles (MPPM) was fabricated for cancerous cells intracellular drug release. Deca-lysine sequence (K10), a type of cell-penetrating peptide, was synthesized and terminated with azido-glycine. Then a new kind of molecule, alkyne modified doxorubicin (DOX) connecting through disulfide bond (DOX-SS-alkyne), was synthesized. After coupling via Cu-catalyzed azide-alkyne cycloaddition (CuAAC) click chemistry reaction, reduction-sensitive peptide-guided prodrug was obtained. Due to the amphiphilic property of the prodrug, it can assemble to form micelles. To prevent the nanocarriers from unspecific cellular uptake, the prodrug micelles were subsequently modified with 2,3-dimethyl maleic anhydride to obtain MPPM with a negatively charged outer shell. In vitro studies showed that MPPM could be shielded from cells under psychological environment. However, when arriving at mild acidic tumor site, the cell-penetrating capacity of MPPM would be activated by charge reversal of the micelles via hydrolysis of acid-labile β-carboxylic amides and regeneration of K10, which enabled efficient internalization of MPPM by tumor cells as well as following glutathione- and protease-induced drug release inside the cancerous cells. Furthermore, since the guide peptide sequences can be accurately designed and synthesized, it can be easily changed for various functions, such as targeting peptide, apoptotic peptide, even aptamers, only need to be terminated with azido-glycine. This method can be used as a template for reduction-sensitive peptide-guided prodrug for cancer therapy.

On the concept of critical surface excess of micellization.

PubMed

Talens-Alesson, Federico I

2010-11-16

The critical surface excess of micellization (CSEM) should be regarded as the critical condition for micellization of ionic surfactants instead of the critical micelle concentration (CMC). There is a correspondence between the surface excesses Γ of anionic, cationic, and zwitterionic surfactants at their CMCs, which would be the CSEM values, and the critical association distance for ionic pair association calculated using Bjerrum's correlation. Further support to this concept is given by an accurate method for the prediction of the relative binding of alkali cations onto dodecylsulfate (NaDS) micelles. This method uses a relative binding strength parameter calculated from the values of surface excess Γ at the CMC of the alkali dodecylsulfates. This links both the binding of a given cation onto micelles and the onset for micellization of its surfactant salt. The CSEM concept implies that micelles form at the air-water interface unless another surface with greater affinity for micelles exists. The process would start when surfactant monomers are close enough to each other for ionic pairing with counterions and the subsequent assembly of these pairs becomes unavoidable. This would explain why the surface excess Γ values of different surfactants are more similar than their CMCs: the latter are just the bulk phase concentrations in equilibrium with chemicals with different hydrophobicity. An intriguing implication is that CSEM values may be used to calculate the actual critical distances of ionic pair formation for different cations, replacing Bjerrum's estimates, which only discriminate by the magnitude of the charge.

Casein Aggregates Built Step-by-Step on Charged Polyelectrolyte Film Surfaces Are Calcium Phosphate-cemented*

PubMed Central

Nagy, Krisztina; Pilbat, Ana-Maria; Groma, Géza; Szalontai, Balázs; Cuisinier, Frédéric J. G.

2010-01-01

The possible mechanism of casein aggregation and micelle buildup was studied in a new approach by letting α-casein adsorb from low concentration (0.1 mg·ml−1) solutions onto the charged surfaces of polyelectrolyte films. It was found that α-casein could adsorb onto both positively and negatively charged surfaces. However, only when its negative phosphoseryl clusters remained free, i.e. when it adsorbed onto a negative surface, could calcium phosphate (CaP) nanoclusters bind to the casein molecules. Once the CaP clusters were in place, step-by-step building of multilayered casein architectures became possible. The presence of CaP was essential; neither Ca2+ nor phosphate could alone facilitate casein aggregation. Thus, it seems that CaP is the organizing motive in the casein micelle formation. Atomic force microscopy revealed that even a single adsorbed casein layer was composed of very small (in the range of tens of nanometers) spherical forms. The stiffness of the adsorbed casein layer largely increased in the presence of CaP. On this basis, we can imagine that casein micelles emerge according to the following scheme. The amphipathic casein monomers aggregate into oligomers via hydrophobic interactions even in the absence of CaP. Full scale, CaP-carrying micelles could materialize by interlocking these casein oligomers with CaP nanoclusters. Such a mechanism would not contradict former experimental results and could offer a synthesis between the submicelle and the block copolymer models of casein micelles. PMID:20921229

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

PubMed Central

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; DuRoss, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-01-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1−/−) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1−/− cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders. PMID:27572704

One-step synthesis and self-assembly behavior of thermo-responsive star-shaped β-cyclodextrin-(P(MEO2MA- co-PEGMA))21 copolymers

NASA Astrophysics Data System (ADS)

Wei, Lulu; Lu, Beibei; Li, Lei; Wu, Jianning; Liu, Zhiyong; Guo, Xuhong

2017-09-01

A novel β-cyclodextrin-poly(2-(2-methoxyethoxy)ethyl methacrylate)- co-poly(ethylene glycol) methacrylate (abbreviated as: β-CD-(P(MEO2MA- co-PEGMA))21) was prepared by using the one-step strategy, and then the star-shaped copolymers were used in the atom transfer radical polymerization (ATRP). The structure of star-shaped β-CD-(P(MEO2MA- co-PEGMA))21 copolymers were studied by FTIR, 1H NMR and gel permeation chromatography (GPC). The star-shaped copolymers could self-assembled into micelles in aqueous solution owing to the outer amphiphilic β-CD as a core and the hydrophilic P(MEO2MA- co-PEGMA) segments as a shell. These thermo-responsive starshaped copolymers micelles exhibited lower critical solution temperature (LCST) in water, which could be finely tuned by changing the feed ratio of MEO2MA to PEGMA. The LCST of star-shaped β-CD-(P(MEO2MA- co-PEGMA))21 copolymer micelles were increased from 35°C to 58°C with the increasing content of PEGMA. The results were investigated by DLS and TEM. When the temperature was higher than corresponding LCSTs, the micelles started to associate and form spherical nanoparticles. Therefore, β-CD-(P(MEO2MA- co-PEGMA))21 star-shaped copolymer micelles could be potentially applied in nano-carrier, nano-reactor, smart materials and biomedical fields.

Celecoxib Encapsulation in β-Casein Micelles: Structure, Interactions, and Conformation.

PubMed

Turovsky, Tanya; Khalfin, Rafail; Kababya, Shifi; Schmidt, Asher; Barenholz, Yechezkel; Danino, Dganit

2015-07-07

β-Casein is a 24 kDa natural protein that has an open conformation and almost no folded or secondary structure, and thus is classified as an intrinsically unstructured protein. At neutral pH, β-casein has an amphiphilic character. Therefore, in contrast to most unstructured proteins that remain monomeric in solution, β-casein self-assembles into well-defined core-shell micelles. We recently developed these micelles as potential carriers for oral administration of poorly water-soluble pharmaceuticals, using celecoxib as a model drug. Herein we present deep and precise insight into the physicochemical characteristics of the protein-drug formulation, both in bulk solution and in dry form, emphasizing drug conformation, packing properties and aggregation state. In addition, the formulation is extensively studied in terms of structure and morphology, protein/drug interactions and physical stability. Particularly, NMR measurements indicated strong drug-protein interactions and noncrystalline drug conformation, which is expected to improve drug solubility and bioavailability. Small-angle X-ray scattering (SAXS) and cryogenic transmission electron microscopy (cryo-TEM) were combined for nanostructural characterization, proving that drug-protein interactions lead to well-defined spheroidal micelles that become puffier and denser upon drug loading. Dynamice light scattering (DLS), turbidity measurements, and visual observations complemented the analysis for determining formulation structure, interactions, and stability. Additionally, it was shown that the loaded micelles retain their properties through freeze-drying and rehydration, providing long-term physical and chemical stability. Altogether, the formulation seems greatly promising for oral drug delivery.

PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

NASA Astrophysics Data System (ADS)

Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; Duross, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

2016-08-01

2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1-/-) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1-/- cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

Fabrication of biodegradable micelles with sheddable poly(ethylene glycol) shells as the carrier of 7-ethyl-10-hydroxy-camptothecin.

PubMed

Guo, Qian; Luo, Ping; Luo, Yu; Du, Fang; Lu, Wei; Liu, Shiyuan; Huang, Jin; Yu, Jiahui

2012-12-01

Biodegradable micelles with sheddable poly(ethylene glycol) shells were fabricated based on poly(ethylene glycol)-block-poly(γ-benzyl L-glutamate) (mPEG-SS-PBLG) diblock copolymer and applied as the carrier of 7-ethyl-10-hydroxy-camptothecin (SN-38) in order to enhance its solubility and stability in aqueous media. The diblock polymer was designed to have the hydrophilic PEG moiety and hydrophobic PBLG moiety linked by biodegradable disulfide bond, so in reducing environment the PEG shells can be detached. The polymer was able to form the micelles of nano-scale in aqueous media, suggesting their passive targeting potential to tumor tissue. Water-insoluble antitumor drug, SN-38, was easily encapsulated into mPEG-SS-PBLG nanomicelles by lyophilization method. When setting theoretical drug loading content at 10 wt%, the drug encapsulation efficiency (EE) was assayed as 73.5%. Owing to the disulfide bond in mPEG-SS-PBLG, intense release of SN-38 occurred in the presence of dithiothreitol (DTT) at the concentration of simulating the intracellular condition, however, micelles showed gradual release of SN-38 in the absence of DTT. Also, the mPEG-SS-PBLG micelles effectively protected the active lactone ring of SN-38 from hydrolysis under physiological condition. Compared with free SN-38, SN-38-loaded nanomicelles showed essentially decreased cytotoxicity against L929 cell line in 24h, bare mPEG-SS-PBLG nanomicelles showed almost non-toxicity. Copyright © 2012 Elsevier B.V. All rights reserved.

Dynamics of adsorption in micellar and non micellar solutions of derivatives of lysosomotropic substances.

PubMed

Dopierala, Katarzyna; Prochaska, Krystyna

2010-04-22

Dynamics of adsorption in micellar and non micellar solutions of derivatives of lysosomotropic substances was studied. The following compounds were considered in our research work: alkyl N,N-dimethyl-alaninates methobromides (DMALM-n), alkyl N,N-dimethylglycinates methobromides (DMGM-n), fatty acids N,N-dimethylaminoethylesters methobromides (DMM-n), fatty acids N,N-dimethylaminopropylesters methobromides (DMPM-n), fatty acids 1-dimethylamino-2-propyl methobromides (DMP(2)M-n), and derivatives of aminoesters with double alkyl chains (M(2)M-n). The examined compounds show interesting biological properties which can be useful, especially in medicine. The exact mechanism of interaction of such compounds with biological membrane is not fully known. However, it is supposed that the presence of micelles has an important role in biological systems. In this paper we show the results of dynamic surface tension measurements in solutions containing the investigated compounds at concentrations above and below cmc. Moreover, we analyzed the influence of the chemical structure of molecules on the diameters of the micelles formed in the solutions. It was found that adsorption dynamics for the studied compounds is strongly affected by the chemical structure of the considered derivatives, especially by the presence of the ester bond, linearity of the molecule, as well as its hydrophobicity. The obtained results show that the structure of the bromide M(2)M-n with two short hydrocarbon chains favors a faster and more efficient adsorption of the molecules at the air/water interface, compared with compounds having one long alkyl chain. Moreover, the double chained derivatives of the M(2)M-n type do not form typical spherical micelles but bilayer structures probably exist in these solutions. The micelles present in the solutions influence the dynamics of adsorption drastically. Moreover, the obtained results indicated that the compounds with especially high biological activity form rather small aggregates. Copyright 2010 Elsevier B.V. All rights reserved.

Photo-responsive polymeric micelles.

PubMed

Huang, Yu; Dong, Ruijiao; Zhu, Xinyuan; Yan, Deyue

2014-09-07

Photo-responsive polymeric micelles have received increasing attention in both academic and industrial fields due to their efficient photo-sensitive nature and unique nanostructure. In view of the photo-reaction mechanism, photo-responsive polymeric micelles can be divided into five major types: (1) photoisomerization polymeric micelles, (2) photo-induced rearrangement polymeric micelles, (3) photocleavage polymeric micelles, (4) photo-induced crosslinkable polymeric micelles, and (5) photo-induced energy conversion polymeric micelles. This review highlights the recent advances of photo-responsive polymeric micelles, including the design, synthesis and applications in various biomedical fields. Especially, the influence of different photo-reaction mechanisms on the morphology, structure and properties of the polymeric micelles is emphasized. Finally, the possible future directions and perspectives in this emerging area are briefly discussed.

Diblock Copolymer Micelles and Supported Films with Noncovalently Incorporated Chromophores: A Modular Platform for Efficient Energy Transfer

DOE PAGES

Adams, Peter G.; Collins, Aaron M.; Sahin, Tuba; ...

2015-04-08

Here we report generation of modular, artificial light-harvesting assemblies where an amphiphilic diblock copolymer, poly(ethylene oxide)-block-poly(butadiene), serves as the framework for noncovalent organization of BODIPY-based energy donor and bacteriochlorin-based energy acceptor chromophores. The assemblies are adaptive and form well-defined micelles in aqueous solution and high-quality monolayer and bilayer films on solid supports, with the latter showing greater than 90% energy transfer efficiency. Ultimately, this study lays the groundwork for further development of modular, polymer-based materials for light harvesting and other photonic applications.

Casein micelles and their internal structure.

PubMed

de Kruif, Cornelis G; Huppertz, Thom; Urban, Volker S; Petukhov, Andrei V

2012-01-01

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 6M 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(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(-1) In the nanocluster model, the casein micelle is considered as a (homogeneous) matrix of caseins in which the colloidal calcium phosphate (CCP) nanoclusters are dispersed as very small (about 2 nm) "cherry stones" at an average distance of 18.6 nm. Attached to the surface of the nanoclusters are the centers of phosphorylation (3-5 nearby phosphorylated amino acid residues) of the caseins. The tails of the caseins, much larger than the CCP clusters, then associate to form a protein matrix, which can be viewed as polymer mesh with density fluctuations at the 2 nm scale. The association of the tails is driven by a collection of weak interactions. We explicitly use weak interactions as a collective term for hydrophobic interactions, hydrogen bonding, ion bonding, weak electrostatic Van der Waals attraction and other factors (but not the strong calcium phosphate interaction) leading to self association. The association is highly cooperative and originates in the weak interactions. It is the cooperativety that leads to a stable casein micelle. Invariably, κ-casein is thought to limit the process of self association leading to stabilization of the native casein micelle. Copyright © 2012 Elsevier B.V. All rights reserved.

Casein micelles and their internal structure

DOE Office of Scientific and Technical Information (OSTI.GOV)

De Kruif, Cornelis G; Huppertz, Thom; Urban, Volker S

2012-01-01

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 presentmore » 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) nanoclusters are dispersed as very small (about 2 nm) 'cherry stones' at an average distance of 18.6 nm. Attached to the surface of the nanoclusters are the centers of phosphorylation (3-5 nearby phosphorylated amino acid residues) of the caseins. The tails of the caseins, much larger than the CCP clusters, then associate to form a protein matrix, which can be viewed as polymer mesh with density fluctuations at the 2 nm scale. The association of the tails is driven by a collection of weak interactions. We explicitly use weak interactions as a collective term for hydrophobic interactions, hydrogen bonding, ion bonding, weak electrostatic Van der Waals attraction and other factors (but not the strong calcium phosphate interaction) leading to self association. The association is highly cooperative and originates in the weak interactions. It is the cooperativety that leads to a stable casein micelle. Invariably, K-casein is thought to limit the process of self association leading to stabilization of the native casein micelle.« less

Nonlinear oscillatory rheology and structure of wormlike micellar solutions and colloidal suspensions

NASA Astrophysics Data System (ADS)

Gurnon, Amanda Kate

The complex, nonlinear flow behavior of soft materials transcends industrial applications, smart material design and non-equilibrium thermodynamics. A long-standing, fundamental challenge in soft-matter science is establishing a quantitative connection between the deformation field, local microstructure and macroscopic dynamic flow properties i.e., the rheology. Soft materials are widely used in consumer products and industrial processes including energy recovery, surfactants for personal healthcare (e.g. soap and shampoo), coatings, plastics, drug delivery, medical devices and therapeutics. Oftentimes, these materials are processed by, used during, or exposed to non-equilibrium conditions for which the transient response of the complex fluid is critical. As such, designing new dynamic experiments is imperative to testing these materials and further developing micromechanical models to predict their transient response. Two of the most common classes of these soft materials stand as the focus of the present research; they are: solutions of polymer-like micelles (PLM or also known as wormlike micelles, WLM) and concentrated colloidal suspensions. In addition to their varied applications these two different classes of soft materials are also governed by different physics. In contrast, to the shear thinning behavior of the WLMs at high shear rates, the near hard-sphere colloidal suspensions are known to display increases, sometimes quite substantial, in viscosity (known as shear thickening). The stress response of these complex fluids derive from the shear-induced microstructure, thus measurements of the microstructure under flow are critical for understanding the mechanisms underlying the complex, nonlinear rheology of these complex fluids. A popular micromechanical model is reframed from its original derivation for predicting steady shear rheology of polymers and WLMs to be applicable to weakly nonlinear oscillatory shear flow. The validity, utility and limits of this constitutive model are tested by comparison with experiments on model WLM solutions. Further comparisons to the nonlinear oscillatory shear responses measured from colloidal suspensions establishes this analysis as a promising, quantitative method for understanding the underlying mechanisms responsible for the nonlinear dynamic response of complex fluids. A new experimental technique is developed to measure the microstructure of complex fluids during steady and transient shear flow using small-angle neutron scattering (SANS). The Flow-SANS experimental method is now available to the broader user communities at the NIST Center for Neutron Research, Gaithersburg, MD and the Institut Laue-Langevin, Grenoble, France. Using this new method, a model shear banding WLM solution is interrogated under steady and oscillatory shear. For the first time, the flow-SANS methods identify new metastable states for shear banding WLM solutions, thus establishing the method as capable of probing new states not accessible using traditional steady or linear oscillatory shear methods. The flow-induced three-dimensional microstructure of a colloidal suspension under steady and dynamic oscillatory shear is also measured using these rheo- and flow-SANS methods. A new structure state is identified in the shear thickening regime that proves critical for defining the "hydrocluster" microstructure state of the suspension that is responsible for shear thickening. For both the suspensions and the WLM solutions, stress-SANS rules with the measured microstructures define the individual stress components arising separately from conservative and hydrodynamic forces and these are compared with the macroscopic rheology. Analysis of these results defines the crucial length- and time-scales of the transient microstructure response. The novel dynamic microstructural measurements presented in this dissertation provide new insights into the complexities of shear thickening and shear banding flow phenomena, which are effects observed more broadly across many different types of soft materials. Consequently, the microstructure-rheology property relationships developed for these two classes of complex fluids will aid in the testing and advancement of micromechanical constitutive model development, smart material design, industrial processing and fundamental non-equilibrium thermodynamic research of a broad range of soft materials.

Interactions of surfactants with lipid membranes.

PubMed

Heerklotz, Heiko

2008-01-01

Surfactants are surface-active, amphiphilic compounds that are water-soluble in the micro- to millimolar range, and self-assemble to form micelles or other aggregates above a critical concentration. This definition comprises synthetic detergents as well as amphiphilic peptides and lipopeptides, bile salts and many other compounds. This paper reviews the biophysics of the interactions of surfactants with membranes of insoluble, naturally occurring lipids. It discusses structural, thermodynamic and kinetic aspects of membrane-water partitioning, changes in membrane properties induced by surfactants, membrane solubilisation to micelles and other phases formed by lipid-surfactant systems. Each section defines and derives key parameters, mentions experimental methods for their measurement and compiles and discusses published data. Additionally, a brief overview is given of surfactant-like effects in biological systems, technical applications of surfactants that involve membrane interactions, and surfactant-based protocols to study biological membranes.

Self-Assembly of Two-Dimensional Patchy Colloidal Dumbbells

NASA Astrophysics Data System (ADS)

Nakamura, Kanji; Sato, Masahide

2018-06-01

We study the self-assembly of two-dimensional patchy colloidal dumbbells, which are composed of attractive and repulsive circles. The shape of a colloidal dumbbell is characterized by the ratio of the diameters of the two circles forming it, q, and the dimensionless distance between the centers of mass of the two circles, l. We carry out Monte Carlo simulations and show that various self-assembled structures, micelles, elongated micelles, straight string, a meshlike structure, and large clusters with voids, are formed by changing the combination of q and l. q represents the steric effect of the repulsive part of colloidal dumbbells. l represents the anisotropy of the particle shape and increasing the periphery of attractive part. From our simulations, we find that the shapes of self-assembled structures are more sensitive to q than to l.

Shipment of a photodynamic therapy agent into model membrane and its controlled release: A photophysical approach.

PubMed

Karar, Monaj; Paul, Suvendu; Mallick, Arabinda; Majumdar, Tapas

2018-01-01

Harmine, an efficient cancer cell photosensitizer (PS), emits intense violet color when it is incorporated in well established self assembly based drug carrier formed by cationic surfactants of identical positive charge of head group but varying chain length, namely, dodecyltrimethylammonium bromide (DTAB), tetradecyltrimethylammonium bromide (TTAB) and cetyltrimethylammonium bromide (CTAB). Micelle entrapped drug emits in the UV region when it interacts with non-toxic β-cyclodextrin (β-CD). Inspired by these unique fluorescence/structural switching properties of the anticancer drug, in the present work we have monitored the interplay of the drug between micelles and non-toxic β-CDs. We have observed that the model membranes formed by micelles differing in their hydrophobic chain length interact with the drug differently. Variation in the surfactant chain length plays an important role for structural switching i.e. in choosing a particular structural form of the drug that will be finally presented to their targets. The present study shows that in case of necessity, the bound drug molecule can be removed from its binding site in a controlled manner by the use of non-toxic β-CD and it is exploited to serve a significant purpose for the removal of excess/unused adsorbed drugs from the model cell membranes. We believe this kind of β-CD driven translocation of drugs monitored by fluorescence switching may find possible applications in controlled release of the drug inside cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Using RNA as a tool to modify lipid nanoparticles

NASA Astrophysics Data System (ADS)

Wilner, Samantha E.

Lipid nanoparticles (LNPs) provide an attractive option for therapeutic applications because they can self-assemble and carry a diverse set of cargoes ranging from hydrophobic drugs to small interfering RNA (siRNA). Liposomes and micelles represent two classes of LNPs that have been developed for medicinal purposes; however, active targeting of LNPs to specific tissues and LNP stability in vivo remain significant challenges. We have exploited the structural characteristics and targeting ability of nucleic acids to address these obstacles. Specifically, we have introduced short nucleic acid targeting species, called aptamers, to the surface of stable nucleic acid lipid particles (SNALPs), a subset of liposomes used in siRNA delivery. In this manner, we have actively targeted SNALPs to cancer cells that overexpress the transferrin receptor (TfR). HeLa cells expressing enhanced green fluorescent protein (EGFP) were treated with SNALPs bearing an antiTfR aptamer (C2) that was identified in our lab. C2-conjugated SNALPs showed increased levels of uptake by cells by flow cytometry. More importantly, the enhanced uptake by C2-conjugated SNALPs translated to an increased level of gene knockdown when SNALPs were loaded with anti-EGFP siRNA or anti-Lamin NC siRNA. Expression of EGFP and Lamin NC decreased, respectively. These preliminary studies illustrate that aptamer-conjugated SNALPs can be designed to knock down both endogenous and exogenous genes in cancer cells with high specificity. We have also used nucleic acids to stabilize lipid micelles by introducing short quadruplex forming oligonucleotide sequences at the lipid headgroup. Micelle formation was confirmed via dynamic light scattering, transmission electron microscopy, and small angle X-ray scattering. Micelle stability was assessed using NMR and by a FRET-based assay in the presence of serum proteins. Quadruplex-stabilized micelles demonstrated enhanced stability suggesting that alterations to oligonucleotide headgroup interactions could be used to tune micelle stability. Therefore, we engineered stabilized micelles with an oligonucleotide extension and have shown that the addition of an antisense oligonucleotide leads to micelle destabilization and cargo release. The ability to control particle stability with antisense oligonucleotides represents a new paradigm in the design of programmed nanoscale devices, which we envision will find utility in the development of novel diagnostics and therapeutics.

[Characteristics of the aggregative state of the substrate in the reaction of 5-lipoxygenase oxidation of linoleic acid].

PubMed

Butovich, I A; Kharchenko, O V; Paboka, Iu N; Kazachkov, M G

2001-01-01

5-lipoxygenase (EC 1.13.11.12) oxidizes polyunsaturated fatty acids by molecular oxygen. The enzyme acts in close contact with the cell membranes, which main components are ionic and non-ionic lipids. In order to investigate the kinetic parameters of 5-lipoxygenase reaction in vitro, extremely hydrophobic fatty acid substrate (linoleic acid) should be solubilized in the reaction mixture. We used Lubrol PX ("Sigma" Chem. Co), as a non-ionic detergent consisted of oligoethylene glycol and fatty alcohol. Linoleic acid and Lubrol PX formed mixed micelles thus solubilizing the fatty acid substrate in a buffer with appropriate pH. We have studied the sizes and shapes of mixed micelles Lubrol PX/linoleic acid (aggregates type 1) and Lubrol PX/linoleic acid/SDS (aggregates type 2; SDS was an effective activator of potato tuber 5-lipoxygenase) by means of gel-filtration and laser light scattering techniques. The parameters under investigation were molecular weights, Stocks radii and shapes of the mixed micelles. The average molecular weights and Stocks radii of the mixed micelles type 1 determined by mean of gel-filtration on Sephadex G-200 were 95,142 +/- 5184 Da and 3.45 +/- 0.11 nm, respectively. The same parameters for the mixed micelles type 2 were 73,694 +/- 893 Da and 3.02 +/- 0.02 nm, respectively. The strong similarity in physicochemical parameters for both types of mixed micelles indicated that SDS did not influence the size and shape of mixed micelles of Lubrol PX and linoleic acid. The activatory action of SDS on potato tuber lipoxygenase may be a result of electrostatic effect or direct participation of SDS in enzymatic catalysis. The laser light scattering technique allowed to determine two main fraction of particles in type 1 system with hydrodynamic diameters 2.6 and 5.7 nm and relative contribution to light scattering 13 and 87%, respectively. The particles with d = 5.7 nm were interpreted as the mixed micelles. The particles with d = 2.6 nm were interpreted as isolated molecules of Lubrol PX, linoleic acid and (or) their premicellar aggregates. The data obtained are to be used in creation of reliable physical and mathematical models of 5-lipoxygenase.

Wormlike Chain Theory and Bending of Short DNA

NASA Astrophysics Data System (ADS)

Mazur, Alexey K.

2007-05-01

The probability distributions for bending angles in double helical DNA obtained in all-atom molecular dynamics simulations are compared with theoretical predictions. The computed distributions remarkably agree with the wormlike chain theory and qualitatively differ from predictions of the subelastic chain model. The computed data exhibit only small anomalies in the apparent flexibility of short DNA and cannot account for the recently reported AFM data. It is possible that the current atomistic DNA models miss some essential mechanisms of DNA bending on intermediate length scales. Analysis of bent DNA structures reveal, however, that the bending motion is structurally heterogeneous and directionally anisotropic on the length scales where the experimental anomalies were detected. These effects are essential for interpretation of the experimental data and they also can be responsible for the apparent discrepancy.

Mechanics and statistics of the worm-like chain

NASA Astrophysics Data System (ADS)

Marantan, Andrew; Mahadevan, L.

2018-02-01

The worm-like chain model is a simple continuum model for the statistical mechanics of a flexible polymer subject to an external force. We offer a tutorial introduction to it using three approaches. First, we use a mesoscopic view, treating a long polymer (in two dimensions) as though it were made of many groups of correlated links or "clinks," allowing us to calculate its average extension as a function of the external force via scaling arguments. We then provide a standard statistical mechanics approach, obtaining the average extension by two different means: the equipartition theorem and the partition function. Finally, we work in a probabilistic framework, taking advantage of the Gaussian properties of the chain in the large-force limit to improve upon the previous calculations of the average extension.

Fabrication of Worm-Like Nanorods and Ultrafine Nanospheres of Silver Via Solid-State Photochemical Decomposition

PubMed Central

2009-01-01

Worm-like nanorods and nanospheres of silver have been synthesized by photochemical decomposition of silver oxalate in water by UV irradiation in the presence of CTAB and PVP, respectively. No external seeds have been employed for the synthesis of Ag nanorods. The synthesized Ag colloids have been characterized by UV-visible spectra, powder XRD, HRTEM, and selected area electron diffraction (SAED). Ag nanospheres of average size around 2 nm have been obtained in the presence of PVP. XRD and TEM analyses revealed that top and basal planes of nanorods are bound with {111} facets. Williamson–Hall plot has revealed the presence of defects in the Ag nanospheres and nanorods. Formation of defective Ag nanocrystals is attributed to the heating effect of UV-visible irradiation. PMID:20596513

Reverse micelle-loaded lipid nano-emulsions: new technology for nano-encapsulation of hydrophilic materials.

PubMed

Anton, Nicolas; Mojzisova, Halina; Porcher, Emilien; Benoit, Jean-Pierre; Saulnier, Patrick

2010-10-15

This study presents novel, recently patented technology for encapsulating hydrophilic species in lipid nano-emulsions. The method is based on the phase-inversion temperature method (the so-called PIT method), which follows a low-energy and solvent-free process. The nano-emulsions formed are stable for months, and exhibit droplet sizes ranging from 10 to 200 nm. Hydrophilic model molecules of fluorescein sodium salt are encapsulated in the oily core of these nano-emulsion droplets through their solubilisation in the reverse micellar system. As a result, original, multi-scaled nano-objects are generated with a 'hydrophilic molecule in a reverse-micelles-in-oil-in-water' structure. Once fluorescein has been encapsulated it remains stable, for thermodynamic reasons, and the encapsulation yields can reach 90%. The reason why such complex objects can be formed is due to the soft method used (PIT method) which allows the conservation of the structure of the reverse micelles throughout the formulation process, up to their entrapment in the nano-emulsion droplets. In this study, we focus the investigation on the process itself, revealing its potential and limits. Since the formulation of nanocarriers for the encapsulation of hydrophilic substances still remains a challenge, this study may constitute a significant advance in this field. Copyright 2010 Elsevier B.V. All rights reserved.

αS1-casein, which is essential for efficient ER-to-Golgi casein transport, is also present in a tightly membrane-associated form

PubMed Central

2010-01-01

Background Caseins, the main milk proteins, aggregate in the secretory pathway of mammary epithelial cells into large supramolecular structures, casein micelles. The role of individual caseins in this process and the mesostructure of the casein micelle are poorly known. Results In this study, we investigate primary steps of casein micelle formation in rough endoplasmic reticulum-derived vesicles prepared from rat or goat mammary tissues. The majority of both αS1- and β-casein which are cysteine-containing casein was dimeric in the endoplasmic reticulum. Saponin permeabilisation of microsomal membranes in physico-chemical conditions believed to conserve casein interactions demonstrated that rat immature β-casein is weakly aggregated in the endoplasmic reticulum. In striking contrast, a large proportion of immature αS1-casein was recovered in permeabilised microsomes when incubated in conservative conditions. Furthermore, a substantial amount of αS1-casein remained associated with microsomal or post-ER membranes after saponin permeabilisation in non-conservative conditions or carbonate extraction at pH11, all in the presence of DTT. Finally, we show that protein dimerisation via disulfide bond is involved in the interaction of αS1-casein with membranes. Conclusions These experiments reveal for the first time the existence of a membrane-associated form of αS1-casein in the endoplasmic reticulum and in more distal compartments of the secretory pathway of mammary epithelial cells. Our data suggest that αS1-casein, which is required for efficient export of the other caseins from the endoplasmic reticulum, plays a key role in early steps of casein micelle biogenesis and casein transport in the secretory pathway. PMID:20704729

Formulation of benzoporphyrin derivatives in Pluronics.

PubMed

Chowdhary, Rubinah K; Chansarkar, Namrata; Sharif, Isha; Hioka, Noboru; Dolphin, David

2003-03-01

This study investigates the potential of Pluronics for the formulation of tetrapyrrole-based photosensitizers, with a particular focus on B-ring benzoporphyrin derivatives. The B-ring derivatives have a high tendency to aggregate in aqueous solutions, and this poses a significant formulation problem. Pluronics are ABA-type triblock copolymers composed of a central hydrophobic polypropylene oxide section with two hydrophilic polyethylene oxide sections of equal length at either end. Out of a range of different commercially available block copolymers studied, it was found that the longer the hydrophobic block, the better the stabilization of tetrapyrrolic drugs in monomeric form in aqueous suspensions. Of these the best performance was observed in the micelle-forming Pluronic P123. Micelle size determination by laser light scattering confirmed that particle size in stable Pluronic formulations was around 20 nm. Pluronics such as L122 formed emulsions spontaneously without the need for emulsion stabilizers; emulsions were highly stable at ambient temperatures over several days and also highly effective as potential drug delivery agents.

Responsive polymer-based colloids for drug delivery and bioconversion

NASA Astrophysics Data System (ADS)

Kudina, Olena

Responsive polymer-based colloids (RPBC) are the colloidal structures containing responsive polymeric component which is able to adapt its physico-chemical properties to the environment by undergoing chemical and/or conformational changes. The goal of the dissertation is to develop and characterize several groups of RPBC with different morphological complexity and explore their potential in drug delivery and bioconversion. The role of RPBC morphology for these specific applications is discussed in details. Three groups of RPBC were fabricated: i. polymeric micelles; ii. mixed polymeric micelles; iii. hybrid polymer-inorganic particles. All fabricated RPBCs contain polymeric component in their structure. The dissertation investigates how the changes of the responsive polymeric component properties are reflected in morphologies of RPBC. The first group of RPBC, polymeric micelles, was formed by the self-assembly of amphiphilic invertible polymers (AIPs) synthesized in our group. AIPs self-assemble into invertible micellar assemblies (IMAs) in solvents of different polarity. In this work, IMAs ability to invert the structure as a response to the change in solvent polarity was demonstrated using 1H NMR spectroscopy and SANS. It was shown that the IMAs incorporate hydrophobic cargo either in the core or in the shell, depending on the chemical structure of cargo molecules. Following in vitro study demonstrates that loaded with drug (curcumin) IMAs are cytotoxic to osteosarcoma cells. Mixed polymeric micelles represent another, more complex, RPBC morphologies studied in the dissertation. Mixed micelles were fabricated from AIPs and amphiphilic oligomers synthesized from pyromellitic dianhydride, polyethylene glycol methyl ethers, and alkanols/cholesterol. The combination of selected AIP and oligomers based on cholesterol results in mixed micelles with an increased drug-loading capacity (from 10% w/w loaded curcumin in single component IMAs to 26%w/w in mixed micelles). Even more complex colloids are hybrid polymer-inorganic particles, the third RPBC group studied in dissertation. Material was designed as core--shell particles with superparamagnetic core engulfed by grafted polymer brushes. These particles were loaded with enzymes (cellulases), thus, are turned into enzymogels for cellulose bioconversion. The study demonstrates that such RPBCs can be used multiple times during hydrolysis and provide an about four-fold increase in glucose production in comparison to free enzymes.

Tetronic Star Block Copolymer Micelles: Photophysical Characterisation of Microenvironments and Applicability for Tuning Electron Transfer Reactions.

PubMed

Samanta, Papu; Rane, Sonal; Bahadur, Pratap; Dutta Choudhury, Sharmistha; Pal, Haridas

2018-05-10

Detailed photophysical investigations have been carried out using a probe dye, Coumarin-153 (C153), to understand the microenvironments of micelles formed by the newly introduced Tetronic star block copolymers, T1304 and T1307, having the same polypropylene oxide (PPO) block size but different polyethylene oxide (PEO) block sizes. Ground state absorption, steady-state fluorescence and time-resolved fluorescence measurements have been used to estimate the micropolarity, microviscosity and solvation dynamics within the two micelles. To the best of our knowledge this is the first report on these important physicochemical parameters for this new class of the star block copolymer micelles. Our results indicate that T1307 micelle offers a relatively more polar and less viscous microenvironment in the corona region, compared to T1304. The effect of the two micellar systems has subsequently been investigated on the bimolecular photoinduced electron transfer (ET) reactions between coumarin dyes (electron acceptors) and aromatic amines (electron donors). On correlating the energetics and kinetics of the ET reactions, clear Marcus Inversion (MI) behavior is observed in both the micellar media. Interestingly, the ET rates for all the donor-acceptor pairs are much higher in T1307 than in T1304, and the onset of MI also appears at a relatively higher exergenocity (-Δ G 0 ) in the former micelle (~0.45 eV for T1307) than the latter (~0.37 eV for T1304). Effect of added NaCl salt studied selectively in T1307 micelle, shows that the ET rate decreases significantly along with a shift in the onset of MI toward lower exergenocity region, so that in the presence of 2 M NaCl the system becomes quite comparable to T1304. Based on the observed results, it is realized that the micropolarity and hence the dynamics of ET process can be tuned very effectively either by changing the constitution of the star block copolymer or by using a suitable additive as a modifier of the micellar microenvironment.

Polymeric micellar nanoplatforms for Fenton reaction as a new class of antibacterial agents.

PubMed

Park, Seong-Cheol; Kim, Nam-Hong; Yang, Wonseok; Nah, Jae-Woon; Jang, Mi-Kyeong; Lee, Dongwon

2016-01-10

Reactive oxygen species (ROS) produced by host phagocytes exert antibacterial action against a variety of pathogens and ROS-induced oxidative stress is the governing mechanism for the antibacterial activity of major bactericidal antibiotics. In particular, hydroxyl radical is a strong and nonselective oxidant which can damage biomolecules such as DNA, proteins and lipids. Ferrous ion is known to convert mild oxidant hydrogen peroxide (H2O2) into highly reactive and toxic hydroxyl radicals, referred to as Fenton reaction. Herein, we report a new class of antibacterial agents based on Fenton reaction-performing nanostructures, composed of H2O2-generating polymer (PCAE) and iron-containing ferrocene. Amphiphilic PCAE was designed to incorporate H2O2-generating cinnamaldehyde through acid-cleavable linkages and self-assemble to form thermodynamically stable micelles which could encapsulate ferrocene in their hydrophobic core. All the experiments in vitro display that ferrocene-loaded PCAE micelles produce hydroxyl radicals to kill Escherichia coli and Pseudomonas aeruginosa through membrane damages. Intraperitoneally injected ferrocene-loaded PCAE micelles significantly reduced the lung damages and therefore increased the survival rate of mice infected with drug resistant P. aeruginosa. Given their potent antibacterial activity, ferrocene-loaded PCAE micelles hold great potential as a new class of ROS-manipulating antibacterial agents. Copyright © 2015 Elsevier B.V. All rights reserved.

In situ diselenide-crosslinked polymeric micelles for ROS-mediated anticancer drug delivery.

PubMed

Deepagan, V G; Kwon, Seunglee; You, Dong Gil; Nguyen, Van Quy; Um, Wooram; Ko, Hyewon; Lee, Hansang; Jo, Dong-Gyu; Kang, Young Mo; Park, Jae Hyung

2016-10-01

Stimuli-responsive micelles have emerged as the drug carrier for cancer therapy since they can exclusively release the drug via their structural changes in response to the specific stimuli of the target site. Herein, we developed the in situ diselenide-crosslinked micelles (DCMs), which are responsive to the abnormal ROS levels of tumoral region, as anticancer drug carriers. The DCMs were spontaneously derived from selenol-bearing triblock copolymers consisting of polyethylene glycol (PEG) and polypeptide derivatives. During micelle formation, doxorubicine (DOX) was effectively encapsulated in the hydrophobic core, and diselenide crosslinks were formed in the shell. The DCMs maintained their structural integrity, at least for 6 days in physiological conditions, even in the presence of destabilizing agents. However, ROS-rich conditions triggered rapid release of DOX from the DOX-encapsulating DCMs (DOX-DCMs) because the hydrophobic diselenide bond was cleaved into hydrophilic selenic acid derivatives. Interestingly, after their systemic administration into the tumor-bearing mice, DOX-DCMs delivered significantly more drug to tumors (1.69-fold and 3.73-fold higher amount compared with their non-crosslinked counterparts and free drug, respectively) and effectively suppressed tumor growth. Overall, our data indicate that DCMs have great potential as drug carriers for anticancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improved solubility and oral bioavailability of apigenin via Soluplus/Pluronic F127 binary mixed micelles system.

PubMed

Zhang, Zhenhai; Cui, Changchang; Wei, Fang; Lv, Huixia

2017-08-01

The aim of this study was to develop a novel mix micelles system composing of two biocompatible copolymers of Soluplus ® and Pluronic F127 to improve the solubility, oral bioavailability of insoluble drug apigenin (AP) as model drug. The AP-loaded mixed micelles (AP-M) were prepared by ethanol thin-film hydration method. The formed optimal formulation of AP-M were provided with small size (178.5 nm) and spherical shape at ratio of 4:1 (Soluplus ® :Pluronic F127), as well as increasing solubility of to 5.61 mg/mL in water which was about 3442-fold compared to that of free AP. The entrapment efficiency and drug loading of AP-M were 95.72 and 5.32%, respectively, and a sustained release of AP-M was obtained as in vitro release study indicated. Transcellular transport study showed that the cell uptake of AP was increased in Caco-2 cell transport models. The oral bioavailability of AP-M was 4.03-fold of free AP in SD rats, indicating the mixed micelles of Soluplus ® and Pluronic F127 is an industrially feasible drug delivery system to promote insoluble drug oral absorption in the gastrointestinal tract.

Manipulating interfacial polymer structures through mixed surfactant adsorption and complexation.

PubMed

Cattoz, Beatrice; de Vos, Wiebe M; Cosgrove, Terence; Crossman, Martin; Prescott, Stuart W

2012-04-17

The effects of a nonionic alcohol ethoxylate surfactant, C(13)E(7), on the interactions between PVP and SDS both in the bulk and at the silica nanoparticle interface are studied by photon correlation spectroscopy, solvent relaxation NMR, SANS, and optical reflectometry. Our results confirmed that, in the absence of SDS, C(13)E(7) and PVP are noninteracting, while SDS interacts strongly both with PVP and C(13)E(7) . Studying interfacial interactions showed that the interfacial interactions of PVP with silica can be manipulated by varying the amounts of SDS and C(13)E(7) present. Upon SDS addition, the adsorbed layer thickness of PVP on silica increases due to Coulombic repulsion between micelles in the polymer layer. When C(13)E(7) is progressively added to the system, it forms mixed micelles with the complexed SDS, reducing the total charge per micelle and thus reducing the repulsion between micelle and the silica surface that would otherwise cause the PVP to desorb. This causes the amount of adsorbed polymer to increase with C(13)E(7) addition for the systems containing SDS, demonstrating that addition of C(13)E(7) hinders the SDS-mediated desorption of an adsorbed PVP layer. © 2012 American Chemical Society

Micelle-Triggered β-Hairpin to α-Helix Transition in a 14-Residue Peptide from a Choline-Binding Repeat of the Pneumococcal Autolysin LytA

PubMed Central

Zamora-Carreras, Héctor; Maestro, Beatriz; Strandberg, Erik; Ulrich, Anne S; Sanz, Jesús M; Jiménez, M Ángeles

2015-01-01

Choline-binding modules (CBMs) have a ββ-solenoid structure composed of choline-binding repeats (CBR), which consist of a β-hairpin followed by a short linker. To find minimal peptides that are able to maintain the CBR native structure and to evaluate their remaining choline-binding ability, we have analysed the third β-hairpin of the CBM from the pneumococcal LytA autolysin. Circular dichroism and NMR data reveal that this peptide forms a highly stable native-like β-hairpin both in aqueous solution and in the presence of trifluoroethanol, but, strikingly, the peptide structure is a stable amphipathic α-helix in both zwitterionic (dodecylphosphocholine) and anionic (sodium dodecylsulfate) detergent micelles, as well as in small unilamellar vesicles. This β-hairpin to α-helix conversion is reversible. Given that the β-hairpin and α-helix differ greatly in the distribution of hydrophobic and hydrophilic side chains, we propose that the amphipathicity is a requirement for a peptide structure to interact and to be stable in micelles or lipid vesicles. To our knowledge, this “chameleonic” behaviour is the only described case of a micelle-induced structural transition between two ordered peptide structures. PMID:25917218

Micellization Behavior of Long-Chain Substituted Alkylguanidinium Surfactants

PubMed Central

Bouchal, Roza; Hamel, Abdellah; Hesemann, Peter; In, Martin; Prelot, Bénédicte; Zajac, Jerzy

2016-01-01

Surface activity and micelle formation of alkylguanidinium chlorides containing 10, 12, 14 and 16 carbon atoms in the hydrophobic tail were studied by combining conductivity and surface tension measurements with isothermal titration calorimetry. The purity of the resulting surfactants, their temperatures of Cr→LC and LC→I transitions, as well as their propensity of forming birefringent phases, were assessed based on the results of 1H and 13C NMR, differential scanning calorimetry (DSC), and polarizing microscopy studies. Whenever possible, the resulting values of Krafft temperature (TK), critical micelle concentration (CMC), minimum surface tension above the CMC, chloride counter-ion binding to the micelle, and the standard enthalpy of micelle formation per mole of surfactant (ΔmicH°) were compared to those characterizing alkyltrimethylammonium chlorides or bromides with the same tail lengths. The value of TK ranged between 292 and 314 K and increased strongly with the increase in the chain length of the hydrophobic tail. Micellization was described as both entropy and enthalpy-driven. Based on the direct calorimetry measurements, the general trends in the CMC with the temperature, hydrophobic tail length, and NaCl addition were found to be similar to those of other types of cationic surfactants. The particularly exothermic character of micellization was ascribed to the hydrogen-binding capacity of the guanidinium head-group. PMID:26861309

Reduction-responsive interlayer-crosslinked micelles prepared from star-shaped copolymer via click chemistry for drug controlled release

NASA Astrophysics Data System (ADS)

Dai, Yu; Wang, Hongquan; Zhang, Xiaojin

2017-12-01

To improve the stability of polymeric micelles, here we describe interlayer-crosslinked micelles prepared from star-shaped copolymer via click chemistry. The formation of interlayer-crosslinked micelles was investigated and confirmed by proton nuclear magnetic resonance, Fourier-transform infrared spectroscopy, and fluorescence spectroscopy. The morphology of un-crosslinked micelles and crosslinked micelles observed by transmission electron microscope is both uniform nano-sized spheres (approximately 20 nm). The crosslinking enhances the stability of polymeric micelles and improves the drug loading capacity of polymeric micelles. The interlayer-crosslinked micelles prepared from star-shaped copolymer and a crosslinker containing a disulfide bond are reduction-responsive and can release the drug quickly in the presence of the reducing agents such as glutathione (GSH).

Improved Micellar Formulation for Enhanced Delivery for Paclitaxel.

PubMed

Xu, Jieni; Zhang, Xiaolan; Chen, Yichao; Huang, Yixian; Wang, Pengcheng; Wei, Yuan; Ma, Xiaochao; Li, Song

2017-01-03

We have previously improved the bioactivity of PEG 5k -FTS 2 system by incorporating disulfide bond (PEG 5k -S-S-FTS 2 ) to facilitate the release of farnesyl thiosalicylic acid (FTS).1 Later, fluorenylmethyloxycarbonyl (Fmoc) moiety has been introduced to PEG 5k -FTS 2 system (PEG 5k -Fmoc-FTS 2 ) in order to enhance drug loading capacity (DLC) and formulation stability.2 In this study, we have brought in both disulfide linkage and Fmoc group to PEG 5k -FTS 2 to form a simple PEG 5k -Fmoc-S-S-FTS 2 micellar system. PEG 5k -Fmoc-S-S-FTS 2 conjugate formed filamentous micelles with a ∼10-fold decrease in critical micellar concentration (CMC). Compared with PEG 5k -Fmoc-FTS 2 , our novel system exhibited further strengthened DLC and colloidal stability. More FTS was freed from PEG 5k -Fmoc-S-S-FTS 2 in treated tumor cells compared to PEG 5k -Fmoc-FTS 2 , which was correlated to an increased cytotoxicity of our new carrier in these cancer cells. After loading Paclitaxel (PTX) into PEG 5k -Fmoc-S-S-FTS 2 micelles, it showed more potent efficiency in inhibition of tumor cell proliferation than Taxol and PTX-loaded PEG 5k -Fmoc-FTS 2 . PTX release kinetics of PTX/PEG 5k -Fmoc-S-S-FTS 2 was much slower than that of Taxol and PTX/PEG 5k -Fmoc-FTS 2 in normal release medium. In contrast, in glutathione (GSH)-containing medium, PTX in PEG 5k -Fmoc-S-S-FTS 2 micelles revealed faster and more complete release. Pharmacokinetics and tissue distribution study showed that our PEG 5k -Fmoc-S-S-FTS 2 system maintained PTX in circulation for a longer time and delivered more PTX to tumor sites with less accumulation in major organs. Finally, PTX-loaded PEG 5k -Fmoc-S-S-FTS 2 micelles resulted in a superior therapeutic effect in vivo compared to Taxol and PTX formulated in PEG 5k -Fmoc-FTS 2 micelles.

pH-responsive polymeric micelles of poly(ethylene glycol)-b-poly(alkyl(meth)acrylate-co-methacrylic acid): influence of the copolymer composition on self-assembling properties and release of candesartan cilexetil.

PubMed

Satturwar, Prashant; Eddine, Mohamad Nasser; Ravenelle, François; Leroux, Jean-Christophe

2007-03-01

The objective of the present study was to investigate the influence of chemical structure and molecular weight of pH-sensitive block copolymers on their self-assembling properties, the loading and the release of candesartan cilexetil (CDN). Block copolymers of poly(ethylene glycol) and t-butyl methacrylate, iso-butyl acrylate, n-butyl acrylate or propyl methacrylate were synthesized by atom transfer radical polymerization. pH-sensitivity was obtained by hydrolysis of t-butyl groups. The poorly water-soluble drug CDN was incorporated in the micelles and the in vitro drug release was evaluated as a function of pH. The critical aggregation concentration of hydrolyzed copolymers (pK(a)=6.2-6.6) was higher compared to the unhydrolyzed ones. Dynamic light scattering studies and atomic force microscopy images revealed uniform size micelles with aggregation numbers ranging from 60 to 160. The entrapment efficiency of CDN was generally found to be above 90%, with drug loading levels reaching approximately 20% (w/w). Differential scanning calorimetry studies showed the amorphous nature of entrapped CDN. The release of CDN from pH-sensitive micelles was triggered upon an increase in pH from 1.2 to 7.2. These findings suggest that the PEG-b-poly(alkyl(meth)acrylate-co-methacrylic acid)s can self-assemble to form micelles which exhibit high loading capacities for CDN and release the drug in a pH-dependent fashion.

Synthesis and characterization of a new family of alkylammonium–chromium phosphates with worm-like morphology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Amghouz, Zakariae, E-mail: amghouz.uo@uniovi.es; Departamento de Química Orgánica e Inorgánica, Universidad de Oviedo-CINN, 33006 Oviedo; Espina, Aránzazu

A series of layered alkylammonium–chromium phosphates, formulated as [C{sub n}H{sub 2n+1}NH{sub 3}]Cr(OH)PO{sub 4} (n=2–6), has been synthesized under hydrothermal conditions. The interlayer spacing, increasing linearly with the increase of alkyl-chain length from 13.61 Å (n=2) to 21.20 Å (n=6), is occupied by a double sheet of packed amine molecules with a tilt angle of ca. 51° respect to the inorganic sheet. The powders are constituted by circular plates (diameter=0.5–3 µm, thickness=∼50 nm) with central holes when n=4–6, stacked in axial direction showing worm-like morphologies. The presence of holes, and some corrugated and zig-zag fashions observed on the edge of thinmore » circular plates are the most probable ways for the reduction of the steric tensions between organic and inorganic portions in these hybrid materials. The thermal and thermo-oxidative stability of selected compounds have been studied, including the determination of activation energy data for the decomposition processes. - Graphical abstract: A novel series of layered alkylammonium–chromium phosphates, [C{sub n}H{sub 2n+1}NH{sub 3}]Cr(OH)PO{sub 4} (n=2–6), was obtained and characterized. The interlayer spacing, increasing linearly with the increase of alkyl-chain length, is occupied by a double sheet of packed amine molecules. The powders are constituted by circular plates (diameter=0.5–3 µm, thickness=∼50 nm) with central holes when n=4–6, stacked in axial direction showing worm-like morphologies. - Highlights: • A series of alkylammonium–chromium phosphates has been obtained by the hydrothermal method. • The interlayer spacing increases linearly with the increase of alkyl-chain length. • The interlayer spacing is occupied by a double sheet of packed amine molecules. • The powders are constituted by stacked circular plates showing wormlike morphology. • Thermal behaviour depends on the atmosphere used and the intercalated amine.« less

Protein composition of different sized casein micelles in milk after the binding of lactoferrin or lysozyme.

PubMed

Anema, Skelte G; de Kruif, C G Kees

2013-07-24

Casein micelles with bound lactoferrin or lysozyme were fractionated into sizes ranging in radius from ∼50 to 100 nm. The κ-casein content decreased markedly and the αS-casein/β-casein content increased slightly as micelle size increased. For lactoferrin, higher levels were bound to smaller micelles. The lactoferrin/κ-casein ratio was constant for all micelle sizes, whereas the lactoferrin/αS-casein and lactoferrin/β-casein ratio decreased with increasing micelle size. This indicates that the lactoferrin was binding to the surface of the casein micelles. For lysozyme, higher levels bound to larger casein micelles. The lysozyme/αS-casein and lysozyme/β-casein ratios were nearly constant, whereas the lysozyme/κ-casein ratio increased with increasing micelle size, indicating that lysozyme bound to αS-casein and β-casein in the micelle core. Lactoferrin is a large protein that cannot enter the casein protein mesh; therefore, it binds to the micelle surface. The smaller lysozyme can enter the protein mesh and therefore binds to the more charged αS-casein and β-casein.

Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance

NASA Astrophysics Data System (ADS)

Yi, Xiaoqing; Zhao, Dan; Zhang, Quan; Xu, Jiaqi; Yuan, Gongdao; Zhuo, Renxi; Li, Feng

2017-02-01

Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.

Synthesis of size-controlled acid-resistant hybrid calcium carbonate microparticles as templates for fabricating "micelles-enhanced" polyelectrolyte capsules by the LBL technique.

PubMed

Li, Xiaodong; Hu, Qiaoling; Yue, Linhai; Shen, Jiacong

2006-07-24

Size-controlled, low-dispersed calcium carbonate microparticles were synthesized in the presence of the amphiphilic block copolymer polystyrene-b-poly(acrylic acid) (PS-b-PAA) by modulating the concentration of block copolymer in the reactive system. This type of hybrid microparticles have acid-resistant properties. By investigating the aggregation behaviors of PS-b-PAA micelles by transmission electron microscopy (TEM), the mechanism of hybrid calcium carbonate formation illustrated that the block copolymer served not only as "pseudonuclei" for the growth of calcium carbonate nanocrystals, but also forms the supramicelle congeries, a spherical framework, as templates for calcium carbonate nanocrystal growth into hybrid CaCO(3) particles. Moreover, this pilot study shows that the hybrid microparticle is a novel candidate as a template for fabricating multilayer polyelectrolyte capsules, in which the block copolymer is retained within the capsule interior after core removal under soft conditions. This not only facilitates the encapsulation of special materials, but also provides "micelles-enhanced" polyelectrolyte capsules.

Wheat germ cell-free expression: Two detergents with a low critical micelle concentration allow for production of soluble HCV membrane proteins.

PubMed

Fogeron, Marie-Laure; Badillo, Aurélie; Jirasko, Vlastimil; Gouttenoire, Jérôme; Paul, David; Lancien, Loick; Moradpour, Darius; Bartenschlager, Ralf; Meier, Beat H; Penin, François; Böckmann, Anja

2015-01-01

Membrane proteins are notoriously difficult to express in a soluble form. Here, we use wheat germ cell-free expression in the presence of various detergents to produce the non-structural membrane proteins 2, 4B and 5A of the hepatitis C virus (HCV). We show that lauryl maltose neopentyl glycol (MNG-3) and dodecyl octaethylene glycol ether (C12E8) detergents can yield essentially soluble membrane proteins at detergent concentrations that do not inhibit the cell-free reaction. This finding can be explained by the low critical micelle concentration (CMC) of these detergents, which keeps the monomer concentrations low while at the same time providing the necessary excess of detergent concentration above CMC required for full target protein solubilization. We estimate that a tenfold excess of detergent micelles with respect to the protein concentration is sufficient for solubilization, a number that we propose as a guideline for detergent screening assays. Copyright © 2014 Elsevier Inc. All rights reserved.

Supercooling of water confined in reverse micelles

NASA Astrophysics Data System (ADS)

Spehr, T.; Frick, B.; Grillo, I.; Stühn, B.

2008-03-01

We report on the temperature dependence of the nanosecond-timescale dynamics of the ternary mixture water/AOT/oil with deuterated heptane, toluene or decane as the oil. Water-swollen reverse micelles as formed in such microemulsions allow us to investigate the freezing behaviour of water confined in a soft environment. We report here on the first neutron scattering studies in which the freezing of the confined water and of the oil is followed down to temperatures at which the whole system is frozen. We focus on studies of water confined in three different droplet sizes: by means of small-angle neutron scattering we have determined the radii to be 46, 18, and 7 Å for water to surfactant ratios ω = 40, 12, and 3. From elastic temperature scans by neutron backscattering we deduce a strong supercooling of water confined in the reverse swollen micelles which increases with decreasing droplet size. For the smallest droplets we find a supercooling of more than 45 K compared to bulk water.

Crosslinked self-assemblies of lipoid acid-substituted low molecular weight (1800 Da) polyethylenimine as reductive-sensitive non-viral gene vectors

NASA Astrophysics Data System (ADS)

Chen, Xiaojiao; Yuan, Zhefan; Yi, Xiaoqing; Zhuo, Renxi; Li, Feng

2012-10-01

In this study, amphiphilic polyethylenimine-graft-thioctic acid (PEI-TA) and polyethylenimine-graft-lauric acid (PEI-LA) were synthesized. Both PEI-TA and PEI-LA could self-assemble into micelles. Due to the existence of disulfide-linked rings at the end of hydrophobic moieties, PEI-TA could form stable micelles with disulfide crosslinked cores (PEI-TA-SS). In comparison with the PEI-LA micelle, PEI-TA-SS possessed higher DNA binding ability according to the gel retardation assay and heparin replacement assay. In vitro transfection experiments indicated that PEI-TA-SS showed comparably high transfection efficiency as compared to 25 kDa PEI. More interestingly, the luciferase expression of PEI-TA-SS was superior to that of PEI-LA at low N/P ratio, which might be ascribed to the stronger binding capacity of PEI-TA-SS facilitating the entering of PEI-TA-SS/pDNA complexes into cells.

Pressure effects on enzyme reactions in mainly organic media: alpha-chymotrypsin in reversed micelles of Aerosol OT in octane.

PubMed

Mozhaev, V V; Bec, N; Balny, C

1994-08-01

Biocatalytic transformations in reversed micelles formed by anionic surfactant Aerosol OT in octane have been studied at high pressures by an example of alpha-chymotrypsin-catalyzed hydrolysis of N-carbobenzoxy-L-tyrosine p-nitrophenyl ester and N-succinyl-L-phenylalanine p-nitroanilide. For the first time it has been found that the enzyme retains high activity in these water-in-oil microemulsions up to a pressure of 2 kbar. The value of the activation volume (delta V*) for the enzyme reactions shows a dependence on the water content in the system. When the size of the micellar aqueous inner cavity (as evaluated at 1 atm) approaches the molecular size of alpha-chymotrypsin, delta V* becomes significantly different from the value in aqueous solution and in the micelles with a larger size. Possibilities of regulating the enzyme activity by pressure in systems with a low content of water are discussed.

Association of denatured whey proteins with casein micelles in heated reconstituted skim milk and its effect on casein micelle size.

PubMed

Anema, Skelte G; Li, Yuming

2003-02-01

When skim milk at pH 6.55 was heated (75 to 100 degrees C for up to 60 min), the casein micelle size, as monitored by photon correlation spectroscopy, was found to increase during the initial stages of heating and tended to plateau on prolonged heating. At any particular temperature, the casein micelle size increased with longer holding times, and, at any particular holding time, the casein micelle size increased with increasing temperature. The maximum increase in casein micelle size was about 30-35 nm. The changes in casein micelle size were poorly correlated with the level of whey protein denaturation. However, the changes in casein micelle size were highly correlated with the levels of denatured whey proteins that were associated with the casein micelles. The rate of association of the denatured whey proteins with the casein micelles was considerably slower than the rate of denaturation of the whey proteins. Removal of the whey proteins from the skim milk resulted in only small changes in casein micelle size during heating. Re-addition of beta-lactoglobulin to the whey-protein-depleted milk caused the casein micelle size to increase markedly on heat treatment. The changes in casein micelle size induced by the heat treatment of skim milk may be a consequence of the whey proteins associating with the casein micelles. However, these associated whey proteins would need to occlude a large amount of serum to account for the particle size changes. Separate experiments showed that the viscosity changes of heated milk and the estimated volume fraction changes were consistent with the particle size changes observed. Further studies are needed to determine whether the changes in size are due to the specific association of whey proteins with the micelles or whether a low level of aggregation of the casein micelles accompanies this association behaviour. Preliminary studies indicated lower levels of denatured whey proteins associated with the casein micelles and smaller changes in casein micelle size occurred as the pH of the milk was increased from pH 6.5 to pH 6.7.

Characterization of Mixed Polypeptide Colloidal Particles by Light Scattering

NASA Astrophysics Data System (ADS)

Shuman, Hannah E.; Gaeckle, Grace K.; Gavin, John; Holland, Nolan B.; Streletzky, Kiril A.

2014-03-01

Temperature-dependent polymer surfactants have been developed by connecting three elastin-like polypeptide (ELP) chains to a charged protein domain (foldon), forming a three-armed star polymer. At low temperatures the polymer is soluble, while at higher temperatures it forms micelles. The behavior of mixtures of the three-armed star ELP (E20-Foldon) and H40-Linear ELP chains was analyzed under different salt and protein concentrations and various foldon to linear ELP ratio using Depolarized Dynamic Light Scattering. It was expected that under certain conditions the pure E20-Foldon would form spherical micelles, which upon adding the linear ELP would change in size and possibly shape. The pure E20-Foldon indeed formed largely spherical micelles with Rh of 10-20nm in solutions with 15-100mM salt and protein concentration between 10 μM and 100 μM. For the mixtures of 50 μM E20-Foldon and varying concentrations of H40-Linear in 25mM of salt, it was discovered that low and high H40-Linear concentration (4 μM and 50 μM) had only one transition. For the mixtures with of 10 and 25 μM of H40-Linear the two distinct transition temperatures were observed by spectrophotometry. The first transition corresponded to significantly elongated diffusive particles of apparent Rh of 30-50nm, while the second transition corresponded to slightly anisotropic diffusive particles with apparent Rh of about 20nm. At all H40-Linear concentrations studied, diffusive particles were seen above the second transition. Their radius and ability to depolarize light increased with the increase of H40-Linear concentration.

Molecular dynamics simulation and NMR investigation of the association of the β-blockers atenolol and propranolol with a chiral molecular micelle

NASA Astrophysics Data System (ADS)

Morris, Kevin F.; Billiot, Eugene J.; Billiot, Fereshteh H.; Hoffman, Charlene B.; Gladis, Ashley A.; Lipkowitz, Kenny B.; Southerland, William M.; Fang, Yayin

2015-08-01

Molecular dynamics simulations and NMR spectroscopy were used to compare the binding of two β-blocker drugs to the chiral molecular micelle poly-(sodium undecyl-(L)-leucine-valine). The molecular micelle is used as a chiral selector in capillary electrophoresis. This study is part of a larger effort to understand the mechanism of chiral recognition in capillary electrophoresis by characterizing the molecular micelle binding of chiral compounds with different geometries and charges. Propranolol and atenolol were chosen because their structures are similar, but their chiral interactions with the molecular micelle are different. Molecular dynamics simulations showed both propranolol enantiomers inserted their aromatic rings into the molecular micelle core and that (S)-propranolol associated more strongly with the molecular micelle than (R)-propranolol. This difference was attributed to stronger molecular micelle hydrogen bonding interactions experienced by (S)-propranolol. Atenolol enantiomers were found to bind near the molecular micelle surface and to have similar molecular micelle binding free energies.

pH and redox-responsive mixed micelles for enhanced intracellular drug release.

PubMed

Cai, Mengtan; Zhu, Kun; Qiu, Yongbin; Liu, Xinrong; Chen, Yuanwei; Luo, Xianglin

2014-04-01

In order to prepare pH and redox sensitive micelles, amphiphilic copolymers of poly (epsilon-caprolactone)-b-poly(2-(diethylamino) ethyl methacrylate) (PCL-PDEA) and disulfide-linked poly(ethyl glycol)-poly(epsilon-caprolactone) (mPEG-SS-PCL) were synthesized. The double-sensitive micelles were prepared simply by solvent-evaporating method with the mixed two copolymers. The pH sensitivity of the mixed micelles was confirmed by the change of micelle diameter/diameter distribution measured by dynamic lighting scattering (DLS) and the redox sensitivity of the mixed micelles was testified by the change of micellar morphous observed by scanning electron microscope (SEM). In vitro drug release showed that drug-loaded mixed micelles (mass ratio 5:5) could achieve above 90% of drug release under low pH and reducing condition within 10h. Moreover, the drug-loaded mixed micelles (mass ratio 5:5) showed the largest cellular toxicity compared with other drug-loaded micelles, while blank mixed micelles exhibited no toxicity. These results meant that the mixed micelles composed by the two amphiphilic copolymers can enhance intracellular drug release. It is concluded that the newly developed mixed micelles can serve as a potential drug delivery system for anticancer drugs. Copyright © 2014 Elsevier B.V. All rights reserved.

Diketopyrrolopyrrole Amphiphile-Based Micelle-Like Fluorescent Nanoparticles for Selective and Sensitive Detection of Mercury(II) Ions in Water.

PubMed

Nie, Kaixuan; Dong, Bo; Shi, Huanhuan; Liu, Zhengchun; Liang, Bo

2017-03-07

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 cysteine using NDPP-Hg composite particle.

[Modeling of linoleyl hydroxamic acid influence on lipoxygenases in vitro].

PubMed

Skaterna, T D; Kopich, V M; Tserniuk, V M; Kharchenko, O V

2009-01-01

5-Lipoxygenase (5-LO) (1.13.11.12) demonstrates its activity in membrane-associated state. A system in vitro with increasing quantity of mixed micelle of nonionic detergent Lubrol PX and substrate--linoleic acid (LA) was used for understanding of 5-LO catalytic activity mechanism, which depends on the membrane environment. Physical parameters of micelles with molar ratio LA-Lubrol PX = 0.3:1 and micelles with 5-LO inhibitor--linoleyl hydroxamic acid (LHA), LA and Lubrol PX (0.03:0.3:1) were characterized by gel-filtration method on Sephadex G-200. It was determined, that Stock's radii were 4.83-5.79 nm for micelles with total LA--50-2000 microM and average molecular mass--177 000-212 000 Da. The presence of 10 microM LHA has no influence on physical parameters of the system. Influence of LHA on kinetic parameters of LA oxidation reaction catalized by potato tubers 5-LO in characterized mixed micelle system was also studied. Substrate dependences curves of 5-LO LA oxidation steady-state rates under conditions of the mixed micelle with ratio LA-lubrol PX = 0.3:1, LHA-LA-Lubrol PX = 0.03:0.3:1 and LHA-LA-Lubrol PX = 0.12:0.3:1 were typical of the substrate inhibition. The presence of inhibitor had no effect on the number of additional substrate molecules--LA which contact with enzyme-substrate complex and decreased V(max) essentially. To predict further inhibitor transformation in the cell the influence of 13-hydroperoxy- and 13-hydroxy LHA on potato tubers 5-LO and porcine leucocyte 12-LO was investigated. It was established that LHA oxidized forms displayed as no less effective inhibitors of the analyzed enzymes; 13-hydroperoxy LHA efficiency increased by an order (IC50 was 0.7 microM) for 12-LO. The possibility of 5-LO to oxidize inhibitor LHA under 50 microM phosphatidic acid at pH 5.0 was demonstrated.

Selective tuning of the self-assembly and gelation of a hydrophilic poloxamine by cyclodextrins.

PubMed

González-Gaitano, Gustavo; da Silva, Marcelo A; Radulescu, Aurel; Dreiss, Cécile A

2015-05-26

Complexes formed between cyclodextrins (CDs) and polymers - pseudopolyrotaxanes (PPRs) - are the starting point of a multitude of supramolecular structures, which are proposed for a wide range of biomedical and technological applications. In this work, we investigate the complexation of a range of cyclodextrins with Tetronic T1307, a four-arm block copolymer of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) with a pH-responsive central ethylene diamine spacer, and its impact on micellization and the sol-gel transition. At low concentrations, small-angle neutron scattering (SANS) combined with dynamic light scattering (DLS) measurements show the presence of spherical micelles with a highly hydrated shell and a dehydrated core. Increasing the temperature leads to more compact micelles and larger aggregation numbers, whereas acidic conditions induce a shrinking of the micelles, with fewer unimers per micelle and a more hydrated corona. At high concentrations, T1307 undergoes a sol-gel transition, which is suppressed at pH below the pKa,1 (4.6). SANS data analysis reveals that the gels result from a random packing of the micelles, which have an increasing aggregation number and increasingly dehydrated shell and hydrated core with the temperature. Native CDs (α, β, γ-CD) can complex T1307, resulting in the precipitation of a PPR. Instead, modified CDs compete with micellization to an extent that is critically dependent on the nature of the substitution. (1)H and ROESY NMR combined with SANS demonstrate that dimethylated β-CD can thread onto the polymer, preferentially binding to the PO units, thus hindering self-aggregation by solubilizing the hydrophobic block. The various CDs are able to modulate the onset of gelation and the extent of the gel phase, and the effect correlates with the ability of the CDs to disrupt the micelles, with the exception of a sulfated sodium salt of β-CD, which, while not affecting the CMT, is able to fully suppress the gel phase.

Design and Synthesis of Self-Assembled Polymeric Nanoparticles for Cancer Drug Delivery

NASA Astrophysics Data System (ADS)

Logie, Jennifer

Current chemotherapeutics are plagued by poor solubility and selectivity, requiring toxic excipients in formulations and causing a number of dose limiting side effects. Nanoparticle delivery has emerged as a strategy to more effectively deliver chemotherapeutics to the tumour site. Specifically, polymeric micelles enable the solubilization of hydrophobic small molecule drugs within the core and mitigate the necessity of excipients. Notwithstanding the significant progress made in polymeric micelle delivery, translation is limited by poor stability and low drug loading. In this work, a rational design approach is used to chemically modify poly(D,L-lactide-co-2-methyl-2-carboxytrimethylene carbonate)-graft-poly(ethylene glycol) (P(LA-co-TMCC)-g-PEG) in order to overcome these limitations and effectively deliver drug to tumours. The PEG density of the polymer system was optimized to enhance the stability of our polymeric micelles. Higher PEG densities permitted the lyophilization of micelles and enhanced the serum stability of the system. To increase the drug loading of our system, we facilitated specific intermolecular interactions within the micelle core. For drugs that form colloidal aggregates, such as pentyl-PABC doxazolidine, polymers were used to stabilize the colloidal core against aggregation and protein adsorption. For more challenging molecules, where self-assembly cannot be controlled, such as docetaxel, we modified the polymeric backbone with a peptide from the binding site of the drug to achieve loadings five times higher than those achieved in conventional micelle systems. This novel docetaxel nanoparticle was assessed in vivo in an orthotopic mouse model of breast cancer, where it showed a wider therapeutic index than the conventional ethanolic polysorbate 80 formulation. The improved tolerability of this formulation enabled higher dosing regimens and led to heightened efficacy and survival in this mouse model. Combined, these studies validated P(LA-co-TMCC)-g-PEG nanoparticles as an effective delivery vehicle for two chemotherapeutics, and presents approaches amenable to the delivery of many other clinically relevant hydrophobic drugs or drug combinations.

Glucose-installed, SPIO-loaded PEG- b-PCL micelles as MR contrast agents to target prostate cancer cells

NASA Astrophysics Data System (ADS)

Theerasilp, Man; Sunintaboon, Panya; Sungkarat, Witaya; Nasongkla, Norased

2017-11-01

Polymeric micelles of poly(ethylene glycol)- block-poly(ɛ-caprolactone) bearing glucose analog encapsulated with superparamagnetic iron oxide nanoparticles (Glu-SPIO micelles) were synthesized as an MRI contrast agent to target cancer cells based on high-glucose metabolism. Compared to SPIO micelles (non-targeting SPIO micelles), Glu-SPIO micelles demonstrated higher toxicity to human prostate cancer cell lines (PC-3) at high concentration. Atomic absorption spectroscopy was used to determine the amount of iron in cells. It was found that the iron in cancer cells treated by Glu-SPIO micelles were 27-fold higher than cancer cells treated by SPIO micelles at the iron concentration of 25 ppm and fivefold at the iron concentration of 100 ppm. To implement Glu-SPIO micelles as a MR contrast agent, the 3-T clinical MRI was applied to determine transverse relaxivities ( r 2*) and relaxation rate (1/ T 2*) values. In vitro MRI showed different MRI signal from cancer cells after cellular uptake of SPIO micelles and Glu-SPIO micelles. Glu-SPIO micelles was highly sensitive with the r 2* in agarose gel at 155 mM-1 s-1. Moreover, the higher 1/ T 2* value was found for cancer cells treated with Glu-SPIO micelles. These results supported that glucose ligand increased the cellular uptake of micelles by PC-3 cells with over-expressing glucose transporter on the cell membrane. Thus, glucose can be used as a small molecule ligand for targeting prostate cancer cells overexpressing glucose transporter.

Supramolecular guests in solvent driven block copolymer assembly: From internally structured nanoparticles to micelles

PubMed Central

Klinger, Daniel; Robb, Maxwell J.; Spruell, Jason M.; Lynd, Nathaniel A.; Hawker, Craig J.

2014-01-01

Supramolecular interactions between different hydrogen-bonding guests and poly(2-vinyl pyridine)-block-poly (styrene) can be exploited to prepare remarkably diverse self-assembled nanostructures in dispersion from a single block copolymer (BCP). The characteristics of the BCP can be efficiently controlled by tailoring the properties of a guest which preferentially binds to the P2VP block. For example, the incorporation of a hydrophobic guest creates a hydrophobic BCP complex that forms phase separated nanoparticles upon self-assembly. Conversely, the incorporation of a hydrophilic guest results in an amphiphilic BCP complex that forms spherical micelles in water. The ability to tune the self-assembly behavior and access dramatically different nanostructures from a single BCP substrate demonstrates the exceptional versatility of the self-assembly of BCPs driven by supramolecular interactions. This approach represents a new methodology that will enable the further design of complex, responsive self-assembled nanostructures. PMID:25525473

Development and evaluation of N-naphthyl-N,O-succinyl chitosan micelles containing clotrimazole for oral candidiasis treatment.

PubMed

Tonglairoum, Prasopchai; Woraphatphadung, Thisirak; Ngawhirunpat, Tanasait; Rojanarata, Theerasak; Akkaramongkolporn, Prasert; Sajomsang, Warayuth; Opanasopit, Praneet

2017-03-01

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.

Effect of counterions on the shape, hydration, and degree of order at the interface of cationic micelles: the triflate case.

PubMed

Lima, Filipe S; Cuccovia, Iolanda M; Horinek, Dominik; Amaral, Lia Q; Riske, Karin A; Schreier, Shirley; Salinas, Roberto K; Bastos, Erick L; Pires, Paulo A R; Bozelli, José Carlos; Favaro, Denize C; Rodrigues, Ana Clara B; Dias, Luís Gustavo; El Seoud, Omar A; Chaimovich, Hernan

2013-04-02

Specific ion effects in surfactant solutions affect the properties of micelles. Dodecyltrimethylammonium chloride (DTAC), bromide (DTAB), and methanesulfonate (DTAMs) micelles are typically spherical, but some organic anions can induce shape or phase transitions in DTA(+) micelles. Above a defined concentration, sodium triflate (NaTf) induces a phase separation in dodecyltrimethylammonium triflate (DTATf) micelles, a phenomenon rarely observed in cationic micelles. This unexpected behavior of the DTATf/NaTf system suggests that DTATf aggregates have unusual properties. The structural properties of DTATf micelles were analyzed by time-resolved fluorescence quenching, small-angle X-ray scattering, nuclear magnetic resonance, and electron paramagnetic resonance and compared with those of DTAC, DTAB, and DTAMs micelles. Compared to the other micelle types, the DTATf micelles had a higher average number of monomers per aggregate, an uncommon disk-like shape, smaller interfacial hydration, and restricted monomer chain mobility. Molecular dynamic simulations supported these observations. Even small water-soluble salts can profoundly affect micellar properties; our data demonstrate that the -CF3 group in Tf(-) was directly responsible for the observed shape changes by decreasing interfacial hydration and increasing the degree of order of the surfactant chains in the DTATf micelles.

Effect of hydrostatic pressure on gas solubilization in micelles.

PubMed

Meng, Bin; Ashbaugh, Henry S

2015-03-24

Molecular dynamics simulations of anionic sodium decylsulfate and nonionic pentaethylene glycol monodecyl ether micelles in water have been performed to examine the impact of hydrostatic pressure on argon solubilization as a function of pressure. The potential-of-mean force between the micelles and argon demonstrates that nonpolar gases are attracted to the interiors of both micelles. The affinity of argon for micelle interiors, however, decreases with increasing pressure as a result of the comparatively higher molar volume of argon inside assemblies. We evaluate solubility enhancement coefficients, which describe the drop in the solute chemical potential as a function of the micellized surfactant concentration, to quantify the impact of micellization on gas solubilization. While argon is similarly attracted to the hydrophobic cores of both micelles, the gas is more effectively sequestered within nonionic micelles compared with anionic micelles as a result of salting out by charged head groups and accompanying counterions. The solubility enhancement coefficients of both micelles decrease with increasing pressure, reflecting the changing forces observed in the potentials-of-mean force. An analytical liquid drop model is proposed to describe the pressure dependence of argon solubilization within micelles that captures the simulation solubility enhancement coefficients after fitting an effective micelle radius for each surfactant.

Preparation of multilocation reduction-sensitive core crosslinked folate-PEG-coated micelles for rapid release of doxorubicin and tariquidar to overcome drug resistance.

PubMed

Yi, Xiaoqing; Zhao, Dan; Zhang, Quan; Xu, Jiaqi; Yuan, Gongdao; Zhuo, Renxi; Li, Feng

2017-02-24

Herein, we prepared folate-targeting core crosslinked polymeric micelles (CCL/FA) containing multiple disulfide bonds located at the interface and core of the micelles to co-deliver doxorubicin (DOX) and the P-glycoprotein (P-gp) inhibitor tariquidar (TQR) for reversing drug resistance. The stability and redox-responsive behavior of the CCL/FA micelles was evaluated through the changes in morphology, molecular weight and hydrodynamic size. On the one hand, the micelles possessed good stability, which led to the suppression of drug release from the CCL micelles in the physiological environment. On the other hand, under reductive conditions, the CCL micelles collapsed rapidly and accelerated drug release markedly. In vitro cytotoxicity measurements, combined with confocal laser scanning microscopy (CLSM) and flow cytometry, confirmed that the dual-drug-loaded micelles exhibited obviously higher cytotoxicity to MCF-7/ADR-resistant cells than free DOX · HCl, single-drug loaded CCL micelles and nontargeted CCL micelles. The results imply that co-delivering DOX and TQR by CCL/FA micelles may be a promising way of overcoming multidrug resistance in tumor treatments.

Worm-like mesoporous TiO2 thin films templated using comb copolymer for dye-sensitized solar cells with polymer electrolyte

NASA Astrophysics Data System (ADS)

Lee, Jae Hun; Park, Cheol Hun; Jung, Jung Pyo; Kim, Jong Hak

2015-12-01

A comb copolymer consisting of hydrophobic poly(2-[3-(2H-benzotriazol-2-yl)-4-hydroxyphenyl] ethyl methacrylate) (PBEM) and hydrophilic poly(oxyethylene methacrylate) (POEM) is synthesized via one-pot free radical polymerization. The PBEM-POEM comb copolymer is used as an agent to direct the structure toward one consisting of worm-like mesoporous TiO2 (WM-TiO2) films. The selective, preferential interaction between the titania precursor and the hydrophilic POEM chains is responsible for the formation of a well-organized worm-like mesostructure. The morphology of the WM-TiO2 films is characterized by scanning electron microscopy (SEM) and atomic force microscopy (AFM). In particular, the effects of film thickness on the optical and electrochemical properties are systematically investigated. The introduction of the WM-TiO2 layer between the nanocrystalline TiO2 (NC-TiO2) layer and fluorine-doped tin oxide (FTO) glass results in increased transmittance of visible light due to an antireflective property, decreased interfacial resistance and suppressed charge recombination at the interfaces of NC-TiO2/FTO glass. As a result, the photovoltaic conversion efficiency of the dye-sensitized solar cell (DSSC) with a polymer electrolyte is improved from 5.3% to 6.6% at an optimum film thickness (310 nm). The obtained efficiency represents a higher efficiency for the N719-based DSSC with a solvent-free, polymer electrolyte.

Chains are more flexible under tension

PubMed Central

Carrillo, Jan-Michael Y.; Rubinstein, Michael

2010-01-01

The mechanical response of networks, gels, and brush layers is a manifestation of the elastic properties of the individual macromolecules. Furthermore, the elastic response of macromolecules to an applied force is the foundation of the single-molecule force spectroscopy techniques. The two main classes of models describing chain elasticity include the worm-like and freely-jointed chain models. The selection between these two classes of models is based on the assumptions about chain flexibility. In many experimental situations the choice is not clear and a model describing the crossover between these two limiting classes is therefore in high demand. We are proposing a unified chain deformation model which describes the force-deformation curve in terms of the chain bending constant K and bond length b. This model demonstrates that the worm-like and freely-jointed chain models correspond to two different regimes of polymer deformation and the crossover between these two regimes depends on the chain bending rigidity and the magnitude of the applied force. Polymer chains with bending constant K>1 behave as a worm-like chain under tension in the interval of the applied forces f ≤ KkBT/b and as a freely-jointed chain for f ≥ KkBT/b (kB is the Boltzmann constant and T is the absolute temperature). The proposed crossover expression for chain deformation is in excellent agreement with the results of the molecular dynamics simulations of chain deformation and single-molecule deformation experiments of biological and synthetic macromolecules. PMID:21415940

Porous worm-like NiMoO4 coaxially decorated electrospun carbon nanofiber as binder-free electrodes for high performance supercapacitors and lithium-ion batteries

NASA Astrophysics Data System (ADS)

Tian, Xiaodong; Li, Xiao; Yang, Tao; Wang, Kai; Wang, Hongbao; Song, Yan; Liu, Zhanjun; Guo, Quangui

2018-03-01

The peculiar architectures consisting of electrospun carbon nanofibers coaxially decorated by porous worm-like NiMoO4 were successfully fabricated for the first time to address the poor cycling stability and inferior rate capability of the state-of-the-art NiMoO4-based electrodes caused by the insufficient structural stability, dense structure and low conductivity. The porous worm-like structure endows the electrode high capacitance/capacity due to large effective specific surface area and short electron/ion diffusion channels. Moreover, the robust integrated electrode with sufficient internal spaces can self-accommodate volume variation during charge/discharge processes, which is beneficial to the structural stability and integrity. By the virtue of rational design of the architecture, the hybrid electrode delivered high specific capacitance (1088.5 F g-1 at 1 A g-1), good rate capability (860.3 F g-1 at 20 A g-1) and long lifespan with a capacitance retention of 73.9% after 5000 cycles when used as supercapacitor electrode. For lithium-ion battery application, the electrode exhibited a high reversible capacity of 1132.1 mAh g-1 at 0.5 A g-1. Notably, 689.7 mAh g-1 can be achieved even after 150 continuous cycles at a current density of 1 A g-1. In the view of their outstanding electrochemical performance and the cost-effective fabrication process, the integrated nanostructure shows great promising applications in energy storage.

Glycopolymer micelles with reducible ionic cores for hepatocytes-targeting delivery of DOX.

PubMed

Wang, Yanxia; Zhang, Xinge; Yu, Peien; Li, Chaoxing

2013-01-30

A novel galactose-decorated cross-linked micelles (cl-micelles) with ionic cores using cystamine (Cys) as a biodegradable cross-linker was prepared by using block ionomer complexes of poly(ethylene glycol)-b-poly(2-acryloxyethyl-galactose)-b-poly(acrylic acid) (PEG-b-PAEG-b-PAA) and Ca(2+) (PEG-b-PAEG-b-PAA cl-micelles/Cys). Doxorubicin (DOX) was successfully incorporated into the ionic cores of such micelles via electrostatic interactions. Proton nuclear magnetic resonance spectrum and Fourier transform infrared spectrometer indicated galactose ligands were exposed at the micellar surface. The micelles were spherical in shape, with an average size of 100nm. The in vitro release studies confirmed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys accomplished rapid drug release under reducing condition. Remarkably, PEG-b-PAEG-b-PAA cl-micelles/Cys efficiently delivered and released DOX into the cell nucleus of HepG2 cells, and the intensity of fluorescence observed in HepG2 cells was stronger than that incubated with the micelles without galactose ligands. In contrast, little fluorescence was observed in NIH3T3 cells after incubation with PEG-b-PAEG-b-PAA cl-micelles/Cys. Interestingly, cytotoxicity assays showed that DOX-loaded PEG-b-PAEG-b-PAA cl-micelles/Cys retained higher cell inhibition efficiency in HepG2 cells as compared with NIH3T3 cells, and were more potent than the micelles without galactose ligands and the micelles with non degradable cross-links. These results indicate that PEG-b-PAEG-b-PAA cl-micelles/Cys have great potential in liver tumor-targeted chemotherapy. Copyright © 2012 Elsevier B.V. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2015-03-01

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.

Biodegradable self-assembled PEG-PCL-PEG micelles for hydrophobic honokiol delivery: I. Preparation and characterization

NASA Astrophysics Data System (ADS)

Gong, ChangYang; Wei, XiaWei; Wang, XiuHong; Wang, YuJun; Guo, Gang; Mao, YongQiu; Luo, Feng; Qian, ZhiYong

2010-05-01

This study aims to develop self-assembled poly(ethylene glycol)-poly(ɛ-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) micelles to encapsulate hydrophobic honokiol (HK) in order to overcome its poor water solubility and to meet the requirement of intravenous administration. Honokiol loaded micelles (HK-micelles) were prepared by self-assembly of PECE copolymer in aqueous solution, triggered by its amphiphilic characteristic assisted by ultrasonication without any organic solvents, surfactants and vigorous stirring. The particle size of the prepared HK-micelles measured by Malvern laser particle size analyzer were 58 nm, which is small enough to be a candidate for an intravenous drug delivery system. Furthermore, the HK-micelles could be lyophilized into powder without any adjuvant, and the re-dissolved HK-micelles are stable and homogeneous with particle size about 61 nm. Furthermore, the in vitro release profile showed a significant difference between the rapid release of free HK and the much slower and sustained release of HK-micelles. Moreover, the cytotoxicity results of blank micelles and HK-micelles showed that the PECE micelle was a safe carrier and the encapsulated HK retained its potent antitumor effect. In short, the HK-micelles were successfully prepared by an improved method and might be promising carriers for intravenous delivery of HK in cancer chemotherapy, being effective, stable, safe (organic solvent and surfactant free), and easy to produce and scale up.

Preparation and in vivo/in vitro evaluation of formononetin phospholipid/vitamin E TPGS micelles.

PubMed

Cheng, Xudong; Yan, Hongmei; Jia, Xiaobin; Zhang, Zhenhai

2016-01-01

To enhance the formononetin (FN) antitumor effect, we developed a passive targeting FN-contained formulation. FN-contained Vitamin E d-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS)/phospholipid micelles were prepared by the solvent injection method. Particle size, polydispersity, zeta potential, encapsulation efficiency, drug release profile, and micelles morphology were evaluated and characterized by various methods including high-performance liquid chromatography, dynamic light scattering, and transmission electron microscopy. Cellular uptake of micelles was evaluated with fluorescence imaging coupled with HPLC method. Cytotoxicity of FN micelles and free FN was compared using MTT method. In vivo imaging was employed to assess the accumulation of DiR micelles and free DiR at tumor site. The antitumor effect of FN micelles was examined in tumor-bearing mice. The results showed that prepared FN micelles had an average particle diameter of 111.91 ± 5.82 nm with good stability. FN micelles enhanced the cellular uptake and improved cell cytotoxicity than free FN. Furthermore, DiR micelles quickly accumulated at the tumor site than free DiR. FN micelles significantly improved tumor inhibition rate compared to that observed with free FN in tumor-bearing mice with great biosafety. Thus, FN micelles demonstrated a clear treatment advantage and provided an ideal drug administration system to improve the antitumor effect of FN.

Constitutive Models for the Force-Extension Behavior of Biological Filaments

NASA Astrophysics Data System (ADS)

Palmer, J. S.; Castro, C. E.; Arslan, M.; Boyce, M. C.

Biopolymer filaments form the molecular backbone of biological structures throughout the body. The biomechanical response of single filaments yields insight into their individual behavior at the molecular level as well as their concerted networked behavior at the cellular and tissue scales. This paper focuses on modeling approaches for axial force vs. extension behavior of single biopolymer filaments within three stiffness regimes: flexible, semiflexible, and stiff. The end-to-end force-extension behaviors of flexible and semiflexible filaments arise as a result of a reduction in configurational space as the filament is straightened and are captured with entropic models including the freely jointed chain model and the worm-like chain model. As the filament is straightened and the end-to-end distance approaches the filament contour length, the contour length is directly axially extended and an internal energy contribution governs the force-extension behavior in this limiting extension regime. On the other hand, for stiff filaments in originally crimped or kinked configurations, the end-to-end force vs. extension behavior results from the unbending (straightening) of the crimped configuration as governed by an internal energy based elastica approximation which is also complemented by an axial stretching contribution once the end-to-end distance approaches the contour length of the filament. Simplified, analytical force-extension relationships are developed for the worm-like chain model for semiflexible filaments, and for the Euler elastica model for stiffer, wavy fibers. For the case of flexible molecules containing modular folded domains, the influence of force-induced unfolding on the force-extension behavior of single molecules and assemblies of multiple molecules is also presented.

Influence of succinylation on the conformation of yak casein micelles.

PubMed

Yang, Min; Cui, Na; Fang, Yan; Shi, Ying; Yang, Jitao; Wang, Jiangyu

2015-07-15

Succinylation modifies the physicochemical characteristics and improves the functional properties of proteins. This study assessed the effects of succinylation on the conformation of yak casein micelles with seven degree of modification. The results revealed that succinylation contributed to the dissociation of casein micelles. With the increase of succinylated degree, soluble nitrogen and minerals content increased, while casein micelle size and polydispersity index of micelles decreased. Succinylation affected the spatial conformation of yak casein micelles: turn decreased, ß-sheet and α-helix increased, and irregular structure were non-significantly affected. The intrinsic and ANS fluorescence intensity decreased and the maximum emission wavelength shifted red with increasing succinylation. Based on the results, the structure of yak casein micelles was characteristic of the sub-micelle model. Copyright © 2015 Elsevier Ltd. All rights reserved.