Solubilization of Aromatic Hydrocarbons in Ethylene Oxide-Propylene Oxide Triblock Micelles: Location of Solubilizate and its Effect on Micelle Size from 2D NMR and Scattering Techniques

The solubilization of benzene and toluene in micellar solutions and the effects on the micellization and micelle size of ethylene oxide-propylene oxide triblock copolymers were investigated by dynamic light scattering (DLS), small angle neutron scattering (SANS), and 2D NMR spectroscopy. The copolymeric surfactants have the same size as the middle hydrophobic polypropylene oxide block (Mol. Wt. 3250) and varying polyethylene oxide end blocks (30, 40 and 50%). The solubilization and the properties of the micelles in the presence of the solubilizates were investigated; the results reveal that the more hydrophobic copolymer showed better solubilization. The cloud points of the copolymers decreased in the presence of oils; the depression in the cloud point is due to the formation of an electron donor–acceptor complex. DLS shows that the effect of benzene is dominated at high oil concentration. SANS data show that the micelles remain spherical in shape and that the micellar core size does not change with higher benzene concentration; observed changes in the low scattering vector region could be because of some small amount of benzene clusters formed at higher benzene concentration. Finally, the locus of solubilization of the oils in the copolymer micelles was determined via 2D NMR experiments. In all cases, significant nuclear Overhauser effect spectroscopy (NOESY) cross peaks were observed that appeared to correlate well with the expected loci of these solubilizates in micelles. Hence, the noninvasive NOESY technique provides important information on the location of the aromatic solubilizates in these copolymer micelles that depends on the structure of the oils.     

Micellization of synthetic and polysaccharides-based graft copolymers in aqueous media

This review highlights recent advances in the micellization of synthetic graft copolymers and those based on natural precursors, particularly polysaccharides. Synthesis and characterization of a broad range of architectures are discussed, along with different micellization procedures and fundamental micellar characteristics, such as morphology and size. Micelle formation by synthetic graft copolymers in aqueous media is examined in detail for different architectures of nonionic, ionic, and temperature and pH stimuli-responsive “double hydrophilic” copolymers. In this context, the problems associated with unimolecular micelles and the correlations between molecular characteristics are further addressed. In addition to backbone and side chain molecular weights, grafting density and topology are the major parameters that directly influence graft copolymer micellization. A similar overview is provided for graft copolymers based on polysaccharides, such as cellulose, chitosan, dextran, and starch. Finally, an outlook is given on the prospects for further development in this area.     

Poly[N-(2-hydroxypropyl)methacrylamide-block-n-butyl acrylate] micelles in water/DMF mixed solvents

Three diblock copolymers of poly[N-(2-hydroxypropyl)methacrylamide] (poly(HPMA)) and poly(n-butyl acrylate) (poly(BA)) with varying lengths of blocks were prepared by atom transfer radical polymerization. All copolymers were found to be soluble in dimethylformamide (DMF) and poorly soluble or insoluble in water. In water and mixed DMF/H₂O solvents, the copolymers were dispersed in micellar form by controlled addition of water to DMF solutions of copolymers under continuous intensive stirring. The micellar solutions in water were prepared by dialysis of solutions in DMF/H₂O (95 vol% of H₂O) against water. Solution properties of diblock copolymers of poly(HPMA) and poly(BA) were studied using static and dynamic laser light scattering to characterize the behavior of the copolymers at the supramolecular level. The effects of preparation mode, organic solvent (DMF) and copolymer chemical composition on the formation of micelles were studied. While a slower mixing procedure was optimal for copolymers with short poly(HPMA) blocks, a faster mixing was more suitable for copolymers having longer poly(HPMA) blocks. Finally, the dimensions of micelles in water were evaluated. The most compact micelles were prepared from copolymers having short hydrophilic poly(HPMA) blocks. On the other hand, the copolymer with the longest poly(HPMA) block formed micelles with the smallest size and the lowest density.     

Self-assembly of polystyrene-b-poly(4-vinylpyridine) in deoxycholic acid melt

It is well known that amphiphilic block copolymers in selective solvents self-assemble into micellar structures, where solvophilic blocks tend to contact with solvents while solvophobic blocks are shielded from the solvents. Different from the conventional micellization in liquid systems, we report that the block copolymer, polystyrene-b-(4-vinylpyridine) (PS-b-P4VP), can self-assemble in melted deoxycholic acid (DCA) at high temperatures and the structures are retained in “solid state” after being cooled down to room temperature. Probing by transmission electron microscopy (TEM), we found that a series of self-assembled structures, including spherical micelles, wormlike micelles and vesicles can be obtained by varying the length of the block copolymers and the morphologies are dependent on the annealing temperature and time. We also demonstrate how to extract the structures that are trapped in solid state by removing DCA using appropriate solvents. The extracted vesicles, which are loaded with solid molecules, are potential for applications in nanocapsules and controlled release.     

Homopolymer influence on micellar solutions of block copolymer

The influence of polystyrene on the formation of poly(styrene-b-ethylene/propylene) micelles in 5-methyl-2-hexanone was investigated. This solvent is selective for the polystyrene blocks. Static and dynamic light scattering and viscosity measurements were carried out to determine whether polystyrene chains in the micellar solutions cause any change in the thermodynamic functions of micellization or in the structural parameters of the micelles. Two homopolystyrenes of different molar mass were used at a concentration of 10⁻²g cm⁻³. Homopolystyrene seems to slightly favour micelle formation, the lower mass polystyrene having a larger effect. The polystyrene chains do not significantly affect the hydrodynamic size and molar mass of the poly(styrene-b-ethylene/propylene) micelles.     

Poly(ethylene oxide)‐g‐gellan polysaccharide nanocarriers for controlled gastrointestinal delivery of simvastatin

Herein, a novel gellan polysaccharide‐based amphiphilic copolymer was synthesized for the development of simvastatin‐loaded micellar nanoparticles. The nanoparticles were explored for their controlled drug release and improved pharmacodynamic potentials. The copolymer was characterized by Fourier transform infrared spectroscopy (FTIR) and elemental analysis. The onset of copolymer micellization was detected by fluorescence spectroscopy. Simvastatin was loaded into micellar particles by solvent evaporation method and the particles were then characterized by microscopic and light scattering techniques. The physical state of drug was studied by X‐ray diffraction analysis. Pharmacodynamic assessment of the micellar preparations was done on rabbit models. The copolymer formed micellar nanoparticles in water. Critical micellar concentration was 9.12mg/l. The micellar particles (426.8–912.6nm) entrapped a maximum of 18.86% drug. Higher negative zeta potential indicated physical stability of micellar systems. A simple diffusion mechanism was operative in the event of comparatively faster drug release in pH6.8 phosphate buffer solution. No significant drug‐copolymer interaction was traced by FTIR spectroscopy. The amorphization of drug into micellar particles reduced LDL‐cholesterol level by ～45% in hyperlipidemic rabbits and this was about 2.5 times higher than pure drug dispersion. Copolymer micellar nanoparticles of simvastatin could control cholesterol level in hyperlipidemic rabbits and thus had potential in drug delivery applications. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42399.     

Re-assembly behaviors of polystyrene-b-poly(acrylic acid) micelles

The re-assembly behaviors of spherical micelles of the polystyrene-b-poly(acrylic acid) (PS-b-PAA) diblock copolymer in different solvent mixtures were investigated using dynamic light scattering, transmission electron microscopy and atomic force microscopy. Depending on the nature of the solvent, PS-b-PAA micelles re-assembled from spheres to nanorings in toluene or to necklace-like aggregates in water induced by solvent evaporation. Systematic studies suggested that the re-assembly behaviors on a neutral surface are strongly correlated with the micellar surface components, the solvent polarity and the chain length of the micelle corona of the solvated blocks. We proposed that the formation of nanorings from PS-b-PAA micelles in toluene is mainly induced by the dewetting process of the solvent, while the necklace-like structure arises from the hydrogen bonding interactions among the partially dissociated PAA units.     

Temperature dependence of dynamics of solutions of triblock copolymer in a selective solvent

The temperature dependence of dynamic properties of solutions of a triblock copolymer with polystyrene outer blocks and a middle block of fully hydrogenated polybutadiene (M_w=7.0×10⁴ gmol⁻¹, mass fraction of PS 0.28) was studied in a selective solvent for the middle block, n-heptane. In dilute solutions, a gradual decomposition of the flower-like micelles was observed on heating. A more complex behavior was observed in semidilute solutions of the copolymer where three dynamic processes can be reliably extracted from the correlation functions. The fast mode corresponds to the collective diffusion mode of physically interconnected micelles, the broad middle mode is probably due to the tracer diffusion of polydispersed clusters (animal-like structures) formed by random association of the triblock copolymer and the slow mode is probably related to the diffusion of aggregates of insoluble polystyrene impurities. The crossover from relaxational to diffusive behavior was found for samples with c>5.5% (w/v). The scattered light intensity measurements revealed a phase transition for the solution with the concentration 4% (w/v) at a temperature of 79±2°C, which was related to the phase separation of polystyrene homopolymer present in a small amount in the copolymer used.     

High-throughput preparation of complex multi-scale patterns from block copolymer/homopolymer blend films

A simple, straightforward process for fabricating multi-scale micro- and nanostructured patterns from polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP)/poly(methyl methacrylate) (PMMA) homopolymer in a preferential solvent for PS and PMMA is demonstrated. When the PS-b-P2VP/PMMA blend films were spin-coated onto a silicon wafer, PS-b-P2VP micellar arrays consisting of a PS corona and a P2VP core were formed, while the PMMA macrodomains were isolated, due to the macrophase separation caused by the incompatibility between block copolymer micelles and PMMA homopolymer during the spin-coating process. With an increase of PMMA composition, the size of PMMA macrodomains increased. Moreover, the P2VP blocks have a strong interaction with a native oxide of the surface of the silicon wafer, so that the P2VP wetting layer was first formed during spin-coating, and PS nanoclusters were observed on the PMMA macrodomains beneath. Whereas when a silicon surface was modified with a PS brush layer, the PS nanoclusters underlying PMMA domains were not formed. The multi-scale patterns prepared from copolymer micelle/homopolymer blend films are used as templates for the fabrication of gold nanoparticle arrays by incorporating the gold precursor into the P2VP chains. The combination of nanostructures prepared from block copolymer micellar arrays and macrostructures induced by incompatibility between the copolymer and the homopolymer leads to the formation of complex, multi-scale surface patterns by a simple casting process.     

Long-tailed spherical aggregates formed from ABA triblock copolymer by changing the properties of selective solvent

A convenient method of tuning aggregate morphologies from amphiphilic block copolymer by adding second selective solvent is introduced in this paper. Some novel aggregate morphologies, i.e. hierarchical vesicles (and compound spherical micelles) with one or more tails, were formed by introducing a second selective solvent for core-forming blocks into the poly(4-vinyl pyridine)-b-polystyrene-b-poly(4-vinyl pyridine) ABA amphiphilic block copolymer/co-solvent/water systems. Addition of selective solvent (toluene) for core-forming blocks (PS blocks) has significant effect on the aggregate morphologies from the amphiphilic triblock copolymer. The aggregate morphologies changed from spheres to rods, long tailed solid large compound spheres, and to long tailed hierarchical vesicles by adding 0.5, 10 and 30 wt% of toluene to the organic solvent, respectively. There exists an aggregate morphological transition of the long tailed hierarchical vesicles to long tailed solid spheres by decreasing the content of toluene in the organic solvent mixture. The tails disappeared, and irregular vesicular and spherical structures were formed when the toluene content was 20 wt%. The toluene addition is expected to increase the stretching of the core-forming blocks (PS), and to modify the interfacial tension of core-corona interface, which are the main reasons for the aggregate morphology transition. To the best of our knowledge, these tailed vesicles and spherical morphologies have not been found in block copolymer aggregates system up to now.     

Micellar Effect of Ammonium Based Cationic Surfactants on Kinetics of Methylene Blue‐Assisted Ru (III) and Cu (II) Catalyzed Cysteine/Cystine Transformation in Acidic Aqueous Media

Kinetic investigations of cysteine–cystine transformation assisted by model electron acceptor methylene blue (MB) and catalyzed synergistically by Ru (III) and Cu (II) in aqueous media of varying pH, temperature and micellar solutions of two ammonium based cationic surfactants viz. octadecylammonium chloride (OAC) and octadecylpyridine‐2‐ylmethylammonium chloride (OPMAC) were carried out. The homogeneous electron transfer between cysteine and MB was observed to exhibit pH sensitive kinetics that is affected by the presence of ammonium based cationic surfactants. While the postmicellar concentrations of OAC decrease the rate of the cysteine oxidation, the presence of OPMAC micelles was observed to accelerate the said reaction. The observed micellar kinetic effects modeled through quantum mechanical calculations are explained in light of the reactant‐micelle interactions. To the best of our knowledge the synthesis, micellization and micellar catalytic activity of OPMAC are yet to be reported in the literature.     

Alkanol-Induced Micelles of a Very Hydrophilic EO–PO–EO Block Copolymer: Characterization by Spectral and Scattering Methods

The aqueous solution behavior of a PEO–PPO–PEO block copolymer (EO₁₀₃PO₃₉EO₁₀₃), was investigated in the presence of aliphatic alkanols (C₂, C₄, C₆ and C₈). The non-associated polymer chains remain extremely hydrated in water, but aggregation in the form of spherical micelles was evidenced, triggered by the interaction of polymer chains with hydrophobic alkanol. We assume that the hydrophobic interaction between the PPO block of the copolymer and alkanol promotes micellization, which increases further with the introduction of higher chain length species. The critical micellization temperature (CMT), as measured by UV–visible spectroscopy, indicates an interaction of polymer chains with the alkanol bearing a higher chain length, which triggers aggregation. The micelles were characterized by small angle neutron scattering to elucidate the size and related micellar parameters. The gradual increase in the alkanol content increases the aggregation number, though the micelles were spherical in shape. We conclude that ethanol, due to its preferential solubility in the aqueous phase, does not affect the aggregation. The alkanols with chain lengths of C₄–C₈ chain, interact with the PPO block through hydrophobic interaction and shifts the CMTs to lower values. The combined effect of inorganic salt (NaCl) and alkanols show enhanced micellar properties.     

Clustered assembly of Au nanoparticles from spherical diblock copolymer micelles encapsulating Au nanoparticle

Superstructures composed of diblock copolymer micelles and inorganic nanoparticles are quite interesting because the specific arrangement of inorganic nanoparticles within the micellar structure can reveal interesting opportunities in many field of science. In this perspective, we report a simple method to produce clustered assembly of Au nanoparticles in the micelles in attempt to induce plasmonic coupling among multiple Au nanoparticles in the assembled structures. Here, we utilized polystyrene‐block‐poly(acrylic acid), PS‐PAA, micelles containing single Au nanoparticle in the core (Au@PS‐PAA micelles) as building materials to initiate next‐level assembling process. In particular, the addition of HCl to the solution of Au@PS‐PAA micelles affected the overall equilibrium condition as well as kinetic process in the micellar solution. As a result, individual Au@PS‐PAA micelles could be merged together to form more large micelles with inclusion of multiple nanoparticles in the core, the process of which was accompanied with plasmonic coupling of Au nanoparticles. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134, 44693.     

Micelles and networks formed by symmetric triblock copolymers in dilute solutions that are poor solvents for the terminal blocks

Summary A simulation for symmetric triblock copolymers in dilute solution shows a rich variety of structures when the solvent produces a net attractive interaction between the terminal blocks. Depending on the strength of this interaction, the system can form transitory aggregates, large independent micelles, or branched structures in which bridging soluble internal blocks connect dense particles formed by the aggregation of insoluble terminal blocks. The formation of the branched structure with the ABA triblock copolymer can be seen under conditions where the corresponding AB diblock copolymer would provide steric stabilization for a polymer colloid.     

Studies on Micellar Behavior of PEO‐PBO or PEO‐PBO‐PEO Copolymers,or Surface Active Amphiphilic Ionic Liquids in Aqueous Media and Exploration of the Micellar Solutions for Solubilization of Dexamethasone and its Delayed Release

The aggregation behavior of a di‐ and tri‐block copolymers of type PEO‐PBO, PEO‐PBO‐PEO, surface‐active ionic liquid (SAIL) of type 4‐dodecyl‐4‐methylmorpholinium chloride [C₁₂mmor][Cl], and 1‐dodecyl‐1‐methylpyrrolidinium chloride [C₁₂mpyrr][Cl]) in water as well as in 10 mM of a poorly water soluble dexamethasone (dex) aqueous solution was studied by determining the critical micelle concentrations using drug solubilization, surface tension, and isothermal titration calorimetry (ITC) methods. ITC measurements were also made on solutions prepared by mixing the micellar aqueous solutions of copolymers and simple aqueous solutions of SAIL across the mole fractions at three different temperatures (298.15, 308.15, and 318.15 K). The thermodynamic parameters, namely Gibbs free energy (ΔG_m), enthalpy (ΔH_m), and entropy (ΔS_m), of micellization were calculated, and it was observed that the negative ΔG_m and positive ΔS_m for the mixture solutions increase with the increase in mole fraction of SAIL. Otherwise, the micellization is reported to be a spontaneous and highly entropy‐driven process. The dex‐solubilized micellar solutions were mixed with agar to obtain standing gels. The gel samples were dry‐cast into thin films, and the release of dex from films by simple dilution was monitored by UV measurements. The drug release data was fitted to several mechanistic models, and it was inferred that the release mechanism for dex from thin films is non‐Fickian for mixtures and Fickian in copolymer or SAIL micellar aqueous solutions. The transport of dex is diffusion‐controlled with diffusivities of 5.8–12 × 10^?11 m² s^?1 for copolymer micelles, 5–11 × 10^?11 m² s^?1 for micelles of SAIL, and 3–14 × 10^?11 m² s^?1 for the mixed micelles of copolymer and SAIL in aqueous media.     

Nanostructured silica templated by double hydrophilic block copolymers with a comb-like architecture

An original way to synthesize nanostructured materials is to use new structuring agents constituted of double hydrophilic block copolymers (DHBC). The originality of these structuring agents is multiple: in water, the hydrosoluble DHBC copolymers can become amphiphilic and form micelles in specific conditions, i.e. after addition of other molecules or after a change of a physicochemical parameter (pH), which selectively makes one of the blocks insoluble in water. The addition of a silica precursor to a micelle suspension can lead to the formation of hybrid mesostructured materials, precursors for mesoporous silica. The micellization process may be reversible and the micelles can then be removed from the silica materials in an aqueous solution at room temperature after application of a dissociation stimulus, leading to the mesoporous materials. A new original DHBC is used here for silica structuring: instead of a classical linear diblock copolymer, it is a diblock copolymer with a linear polyacid block (PAA) and a poly(ethylene oxide) based neutral block (PAMPEO) with a comb-type architecture. It is synthesized by controlled radical polymerization (RAFT method) which permits a control of the block lengths. It is shown here that these new DHBC polymers can form polyion complex micelles by complexation with a natural polyamine and that the micellization is reversible as a function of the pH. It is also shown that the new pH sensitive micelles can act as structuring agents in the preparation of mesoporous silica materials.     

Poly(allyl glycidyl ether)‐block‐poly(ethylene oxide): A novel promising polymeric intermediate for the preparation of micellar drug delivery systems

Novel diblock copolymers designed for the preparation of micellar drug delivery systems, consisting of hydrophobic poly(allyl glycidyl ether) (PAGE) and hydrophilic poly(ethylene oxide) (PEO), were prepared, and their self‐assembly into micellar structures was studied. Copolymers differing in the length of the polymer blocks were purified and characterized. These amphiphilic copolymers with narrow molecular weight distributions were prepared through the anionic polymerization of allyl glycidyl ether with PEO monomethyl ether sodium salt as the macroinitiator. The PAGE–PEO copolymer readily formed small micelles with narrow size distributions via simple dissolution in water. The addition of pendant double bonds to the hydrophobic part of the chain was intended for further covalent modifications. Catalytic hydrogenation, the radical crosslinking of the micelle core, and the addition of thiol to double bonds of the copolymer were examples of such modifications that were proved to proceed with a quantitative yield for this copolymer. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 201–211, 2005     

Structure and dynamics of a pentablock copolymer of polystyrene-polybutadiene in a butadiene-selective solvent

We have examined solutions of a polystyrene-polybutadiene pentablock copolymer in n-heptane, a strongly selective solvent for polybutadiene. Small angle neutron scattering from 7 to 15% samples reveals domains about 10 nm in radius formed by the association of 200 polystyrene blocks. Dynamic light scattering measurements on 8 and 9% samples showed three modes: a fast diffusive mode related to the collective diffusion in semidilute solutions/gels; a relaxational mode related to the local dynamics of polystyrene domains trapped in the gel formed by bridging the domains with the polybutadiene chains; and a very slow diffusive mode. The relaxational dynamics persisted over the entire temperature range, becoming faster with increasing temperature, indicating a decreased microviscosity at higher temperatures. The slow dynamics seems to be connected with heterogeneities in the physical gel due to microsyneresis and almost disappeared above 50 °C. Macroscopic phase separation into two liquid phases was observed in a dilute solution of the un-associated copolymer, and into a liquid and gel phase at higher concentrations. The absence of flower-like micelles in dilute solutions and the macroscopic phase seperation suggest that the gels in the pentablock are formed by random association of multiplet domains and not by bridging of micellar domains.     

Synthesis and characterization of temperature and pH-responsive pentablock copolymers

A family of amphiphilic ABCBA pentablock copolymers based on commercially available Pluronic^® F127 block copolymers and various amine containing methacrylate monomers was synthesized via Cu(I) mediated controlled radical polymerization. The block architecture and chemical composition of the pentablock copolymers were engineered to exhibit both temperature and pH responsive self-assembly by exploiting the lower critical solution temperature of the poly(ethylene oxide)/poly(propylene oxide) blocks and the polycationic property of the poly(amine methacrylate) blocks, respectively. In aqueous solutions, the pentablock copolymers formed temperature and pH-responsive micelles. Concentrated aqueous solutions of the copolymer formed a pH-responsive, thermoreversible gel phase. The controlled radical synthesis route yielded well-defined copolymers with narrow molecular weight distributions with the benefit of mild reaction conditions. Small angle X-ray scattering, laser light scattering, cryogenic transmission electron microscopy and dynamic mechanical analysis have been used to characterize the self-assembled structures of the micellar solution and gel phases of the aqueous copolymer system. These copolymers have potential applications in controlled drug delivery and non-viral gene therapy due to their tunable phase behavior and biocompatibility.     

Synthesis and self-association in aqueous media of poly(ethylene oxide)/poly(ethyl glycidyl carbamate) amphiphilic block copolymers

New temperature sensitive AB, ABA, and BAB amphiphilic block copolymers consisting of hydrophilic poly(ethylene oxide) and hydrophobic poly(ethyl glycidyl carbamate) blocks were synthesized by anionic polymerization followed by chemical modification reactions. The self-association of the block copolymers in aqueous media was studied by UV-vis spectroscopy and dynamic and static light scattering. The obtained block copolymers spontaneously form micelles in aqueous media. The critical micellization concentration varied from 0.5 to 4 g/L depending on the copolymer architecture and composition. The influence of the temperature upon the self-association of the block copolymers was investigated. The increase of temperature did not affect the value of the critical micellization concentration, but led to the formation of better defined micelles with narrow size distribution.