Polyelectrolyte Block Copolymer Research Articles

Simulation Study of the Conformational Properties of Diblock Polyelectrolytes in Salt Solutions.

Coarse-grained molecular dynamics simulations are performed to understand the behavior of diblock polyelectrolytes in solutions of divalent salt by studying the conformations of chains over a wide range of salt concentrations. The polymer molecules are modeled as bead spring chains with different charged fractions and the counterions and salt ions are incorporated explicitly. Upon addition of a divalent salt, the salt cations replace the monovalent counterions, and the condensation of divalent salt cations onto the polyelectrolyte increases, and the chains favor to collapse. The condensation of ions changes with the salt concentration and depends on the charged fraction. Also, the degree of collapse at a given salt concentration changes with the increasing valency of the counterion due to the bridging effect. As a quantitative measure of the distribution of counterions around the polyelectrolyte chain, we study the radial distribution function between monomers on different polyelectrolytes and the counterions inside the counterion worm surrounding a polymer chain at different concentrations of the divalent salt. Our simulation results show a strong dependence of salt concentration on the conformational properties of diblock copolymers and indicate that it can tune the self-assembly behaviors of such charged polyelectrolyte block copolymers.

In-situ growth and characterization of metal oxide nanoparticles within block-copolymer polyelectrolyte membranes

In-situ growth of nanometer size metal oxide crystallites within polyelectrolyte block-copolymer membranes is demonstrated with example of ZnO loaded Nexar and SEBS films. The proposed method allows for the controlled synthesis of ZnO nanoparticles ranging from 2 to 8 nm uniformly dispersed within the membranes. The fabricated films are characterized with XRD, TEM and HAADF-STEM techniques. It is shown that particles size and shape can be tuned by varying the solvent composition. Addition of methanol favors the growth of smaller-sized ZnO. The proposed method can be applied to produce other metal oxide – polyelectrolyte nanocomposites, which may find various applications ranging from fuel cells and other electrochemical devices to separation membranes and protective barriers.

Polymerization-Induced Self-Assembly of Metallo-Polyelectrolyte Block Copolymers.

Cobaltocenium-containing polyelectrolyte block copolymer nanoparticles were prepared via polymerization-induced self-assembly (PISA) using aqueous dispersion RAFT polymerization. The cationic steric stabilizer was a macromolecular chain-transfer agent (macro-CTA) based on poly (2-cobaltocenium amidoethyl methacrylate chloride) (PCoAEMACl), and the core-forming block was poly(2-hydroxypropyl methacrylate) (PHPMA). Stable cationic spherical nanoparticles were formed in aqueous solution with low dispersity without adding any salts. The chain extension of macro-CTA with HPMA was efficient and fast. The effects of block copolymer compositions, solid content, charge density, and addition of salts were studied. It was found that the degree of polymerization of both the stabilizer PCoAEMACl and the core-forming PHPMA had a strong influence on the size of nanoparticles.

A pH-Sensitive Polymer for Cancer Targeting Prepared by One-Step Modulation of Functional Side Groups

Nanocarriers with pH-sensitive functionality are of great interest in the development of pH-dependent drug release compounds in acidic tumor microenvironments. A new polyelectrolyte block copolymer, poly[(benzyl-L-aspartate)-co-(N-(3-aminopropyl) imidazole-L-aspartamide)]-poly(ethylene glycol) (PABI-PEG), was prepared by one-step modulation to produce pH-sensitive nanocarriers. PABI-PEG formed a stable nanocarrier at pH values above 7.4 and was destabilized in acidic conditions (pH 6.5) through the protonation of the imidazole groups. Docetaxel loaded micelle (DLM) exhibited pH-dependent drug release through structural conversion due to the protonation of the imidazole groups on the PABI block. The critically low micelle concentration of PABI-PEG at physiological pH and the pH-dependent drug release would result to high stability and restrict drug loss during systemic circulation which may lower the toxicity of normal tissue to physiological pH. Additionally, the extracellular tumor pH (<7.0) and early endosomal pH (<6.5) environments triggered the disintegration of micelles, producing higher drug release compared to other normal tissues and blood (pH 7.4). Therefore, PABI-PEG may be a pHsensitive drug delivery method for cancer chemotherapy.

Self-assembly of oppositely charged polyelectrolyte block copolymers containing short thermoresponsive blocks.

The assembly of oppositely charged block copolymers, containing small thermoresponsive moieties, was investigated as a function of salt concentration and temperature. Aqueous solutions of poly-[N-isopropylacrylamide]-b-poly[dimethylaminoethyl methacrylate] (NIPAM44-b-DMAEMA216) and PNIPAM-b-poly[acrylic acid]-b-PNIPAM (NIPAM35-b-AA200-b-NIPAM35) were mixed in equal charge stoichiometry, and analysed by light scattering (LS), NMR spectroscopy and small angle X-ray scattering (SAXS). At room temperature, two different micelle morphologies were found at different salt concentrations. At NaCl concentrations below 0.75 M, complex coacervate core micelles (C3M) with a PNIPAM corona were formed as a result of interpolyelectrolyte complexation. At NaCl concentrations exceeding 0.75 M, the C3M micelles inverted into PNIPAM cored micelles (PCM), containing a water soluble polyelectrolyte corona. This behavior is ascribed to the salt concentration dependence of both the lower critical solution temperature (LCST) of PNIPAM, and the complex coacervation. Above 0.75 M NaCl, the PNIPAM blocks are insoluble in water at room temperature, while complexation between the polyelectrolytes is prevented because of charge screening by the salt. Upon increasing the temperature, both types of micelles display a cloud point temperature (Tcp), despite the small thermoresponsive blocks, and aggregate into hydrogels. These hydrogels consist of a complexed polyelectrolyte matrix with microphase separated PNIPAM domains. Controlling the morphology and aggregation of temperature sensitive polyelectrolytes can be an important tool for drug delivery systems, or the application and hardening of underwater glues.

Structure and solvation thermodynamics of asymmetric poly (acrylic acid)-b-polystyrene polyelectrolyte block copolymer micelle in water: Effect of charge density and chemical composition

Molecular structure and thermodynamic behavior of micelles formed by polyelectrolyte-neutral block copolymer chains, in particular polystyrene-b-poly(acrylic acid) (PS-b-PAA), in salt-free aqueous solution was studied via detailed explicit atomistic molecular dynamics simulations as a function of the copolymer composition (XPS) and the fractional charge (f) of ionizable PAA blocks. Micelle formation occurs via self-aggregation of PS-b-PAA copolymer chains with formation of PS core and PAA corona. The size of the PS core shows power-law dependence with respect to number of PS units per chain with an exponent 0.56 in agreement with scaling relations and experimental observations. The overall size of the micelle increases linearly with XPS. Increase in XPS results in a linear increase in micelle size and change in shape from spherical to prolate. The number of hydrogen bonds, pair correlation functions and various interatomic pair-wise energetic contributions to solvation enthalpy indicate favorable copolymer-water interaction. Micelle solvation is significantly influenced by hydrogen bonding interactions of carboxylic hydrogen atoms with water oxygens. Atom density profiles, solvation enthalpy and correlation functions of copolymer-Na+ ion pairs confirm the existence of micelle in osmotic regime, in agreement with mean-field theory.

Switching the Stiffness of Polyelectrolyte Assembly by Light to Control Behavior of Supported Cells.

Polyelectrolyte block copolymer micelles assembled thin film is switched in response to local photocatalytic reactions on titanium dioxide, resulting in a layer of variable height, stiffness in response to visible light irradiation. Preosteoblasts migrate toward stiffer side of the substrates.

Macrophages Offer A Paradigm Switch for CNS Delivery of Therapeutic Proteins

Active targeted transport of the nanoformulated redox enzyme, catalase, in macrophages attenuates oxidative stress and as such increases survival of dopaminergic neurons in animal models of Parkinson's disease. Optimization of the drug formulation is crucial for the successful delivery in living cells. We demonstrated earlier that packaging of catalase into a polyion complex micelle ('nanozyme') with a synthetic polyelectrolyte block copolymer protected the enzyme against degradation in macrophages and improved therapeutic outcomes. We now report the manufacture of nanozymes with superior structure and therapeutic indices. Synthesis, characterization and therapeutic efficacy of optimal cell-based nanoformulations are evaluated. A formulation design for drug carriers typically works to avoid entrapment in monocytes and macrophages focusing on small-sized nanoparticles with a polyethylene glycol corona (to provide a stealth effect). By contrast, the best nanozymes for delivery in macrophages reported in this study have a relatively large size (≈ 200 nm), which resulted in improved loading capacity and release from macrophages. Furthermore, the cross-linking of nanozymes with the excess of a nonbiodegradable linker ensured their low cytotoxicity, and efficient catalase protection in cell carriers. Finally, the 'alternatively activated' macrophage phenotype (M2) utilized in these studies did not promote further inflammation in the brain, resulting in a subtle but statistically significant effect on neuronal regeneration and repair in vivo. The optimized cross-linked nanozyme loaded into macrophages reduced neuroinflammatory responses and increased neuronal survival in mice. Importantly, the approach for nanoformulation design for cell-mediated delivery is different from the common requirements for injectable formulations.

A feasibility study of a pH sensitive nanomedicine using doxorubicin loaded poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol) micelles.

A polyelectrolyte block copolymer, poly(aspartic acid-graft-imidazole)-block-poly(ethylene glycol) (P(Asp-g-Im)-PEG), with several advantages such as an easy synthesis, having a high molecular weight and the buffer capacity of a zwitterionic polymer backbone compared to poly(histidine) backbones, was presently investigated to evaluate its feasibility as a pH sensitive anticancer nanomedicine. Doxorubicin (DOX) loaded P(Asp-g-Im)-PEG micelles (DPHAIM) were prepared by the bottom flask and diafiltration methods, forming stable pH sensitive nano-systems. DPHAIM with a 28% loading capacity displayed a pH dependent behavior with respect to drug release and cytotoxicity. At pH values below 7.0, the cumulative DOX release and cell cytotoxicity were increased compared to those at physiological pH. Animal imaging after intravenous administration of the micelles revealed their accumulation by passive targeting to tumor tissue compared to other normal tissues. This pH sensitive nanovehicle based on P(Asp-g-Im)-PEG is implicated as a promising anticancer nanomedicine with less toxicity on normal tissues for effective tumor treatment.

Living Unimodal Growth of Polyion Complex Vesicles via Two-Dimensional Supramolecular Polymerization

Understanding the dynamic behavior of molecular self-assemblies with higher-dimensional structures remains a key challenge to obtaining well-controlled and monodispersed structures. Nonetheless, there exist few systems capable of realizing the mechanism of supramolecular polymerization at higher dimensions. Herein, we report the unique self-assembling behavior of polyion complexes (PICs) consisting of poly(ethylene glycol)-polyelectrolyte block copolymer as an example of two-dimensional supramolecular living polymerization. Monodispersed and submicrometer unilamellar PIC vesicles (nano-PICsomes) displayed time-dependent growth while maintaining a narrow size distribution and a unilamellar structure. Detailed analysis of the system revealed that vesicle growth proceeded through the consumption of unit PICs (uPICs) composed of a single polycation/polyanion pair and was able to restart upon the further addition of isolated uPICs. Interestingly, the resulting vesicles underwent dissociation into uPICs in response to mechanical stress. These results clearly frame the growth as a two-dimensional supramolecular living polymerization of uPICs.

Dynamic Swelling of Tunable Full-Color Block Copolymer Photonic Gels via Counterion Exchange

One-dimensionally periodic block copolymer photonic lamellar gels with full-color tunability as a result of a direct exchange of counteranions were fabricated via a two-step procedure comprising the self-assembly of a hydrophobic block-hydrophilic polyelectrolyte block copolymer, polystyrene-b-poly(2-vinyl pyridine) (PS-b-P2VP), followed by sequential quaternization of the P2VP layers in 1-bromoethane solution. Depending on the hydration characteristics of each counteranion, the selective swelling of the block copolymer lamellar structures leads to large tunability of the photonic stop band from blue to red wavelengths. More extensive quaternization of the P2VP block allows the photonic lamellar gels to swell more and red shift to longer wavelength. Here, we investigate the dynamic swelling behavior in the photonic gel films through time-resolved in situ measurement of UV-vis transmission. We model the swelling behavior using the transfer matrix method based on the experimentally observed reflectivity data with substitution of appropriate counterions. These tunable structural color materials may be attractive for numerous applications such as high-contrast displays without using a backlight, color filters, and optical mirrors for flexible lasing.

Polyelectrolyte Complex Optimization for Macrophage Delivery of Redox Enzyme Nanoparticles

We posit that cell-mediated drug delivery can improve transport of therapeutic enzymes to the brain and decrease inflammation and neurodegeneration seen during Parkinson's disease. Our prior works demonstrated that macrophages loaded with nanoformulated catalase ('nanozyme') then parenterally injected protect the nigrostriatum in a murine model of Parkinson's disease. Packaging of catalase into block ionomer complex with a synthetic polyelectrolyte block copolymer precludes enzyme degradation in macrophages. We examined relationships between the composition and structure of block ionomer complexes with a range of block copolymers, their physicochemical characteristics, and loading, release and catalase enzymatic activity in bone marrow-derived macrophages. Formation of block ionomer complexes resulted in improved aggregation stability. Block ionomer complexes with ε-polylysine and poly(L-glutamic acid)-poly(ethylene glycol) demonstrated the least cytotoxicity and high loading and release rates. However, these formulations did not efficiently protect catalase inside macrophages. Nanozymes with polyethyleneimine- and poly(L-lysine)(10)-poly(ethylene glycol) provided the best protection of enzymatic activity for cell-mediated drug delivery.

Stabilization of enzymes-antioxidants by complex and conjugate formation with block copolymers: Prospects for CNS treatment

Nanosized particles with a radius of 16 ± 2 nm based on complexes and conjugates of highly active superoxide dismutase and catalase with polyelectrolyte block copolymer poly(ethyleneimine)-poly(ethylene glycol) and similar bienzyme systems were obtained. Mass spectrometry was used to confirm the crosslinking of enzyme and block copolymer molecules in the nanoparticles that were formed. A significant increase of SOD and catalase stability (up to four times) towards proteolytic degradation under chymotrypsin and trypsin action for 3 h at 37°C was revealed when enzyme-containing nanoparticles were used for experiments. Antioxidant enzymes-containing polyelectrolyte nanoparticles seem to be promising for BBB penetration and CNS drug delivery.

All-conjugated polyelectrolyteblock copolymers

Novel, all-conjugated polyelectrolyte block copolymers of the rod-rod type can be generated in a “grafting from” scheme and exhibit a preferred tendency to self-assemble into layered aggregates both in solution and the solid state. Here, the rigid-rod structure of the individual, complex macromolecules favours the formation of low-curvature vesicular and lamellar aggregates. Our poly(9,9-dialkylfluorene)-b-poly[3-(6-ammoniumhexyl)thiophene] (PF2/6-b-P3TMAHT and PFO-b-P3TMAHT, where PF2/6 and PFO denote 2-(ethyl)hexyl and linear octyl alkyl pendant groups, respectively), and poly(9,9-dialkylfluorene)-b-poly[3-(6-pyridylhexyl)thiophene] (PF2/6-b-P3PyHT and PFO-b-P3PyHT) polyelectrolyte diblock copolymers allow for simple and reliable control of the occurring self-organisation process and the resulting nano-scaled architectures. They are, therefore, promising candidates for application as the active layer in electronic devices or as functional membranes (e.g. for sensor applications). Moreover, the electronic properties of the materials (especially the excitation energy transfer between both blocks) strongly depend on the aggregation state present. Aggregation can be further controlled via addition of oppositely charged surfactants resulting in the formation of ordered polyelectrolyte/surfactant complexes.

PH and ionic strength responsive polyelectrolyte block copolymer micelles prepared by ring opening metathesis polymerization

AbstractWell‐defined amphiphilic block copolymers were prepared by ring opening metathesis polymerization and their stimuli responsive behavior of formed micelles in aqueous solution was investigated. The hydrophobic core of the micelles consists of either a poly[5,6‐bis(ethoxymethyl)bicyclo[2.2.1]hept‐2‐ene]‐block with a glass transition Tg at room temperature or a poly[endo,exo[2.2.1]bicyclohept‐5‐ene‐2,3‐diylbis (phenylmethanone)] with a Tg of 143 °C. For the polyelectrolyte shell, the precursor block poly[endo,exo[2.2.1]bicyclohept‐5‐ene‐2,3‐dicarboxyclic tert‐butylester] was transformed into the free acidic block by cleavage of the tert‐butyl groups using trifluoroacetic acid. Micellar solutions were prepared by dialysis, dissolving the copolymers in dimethyl sulfoxide which was subsequently replaced by water. All polymers form micelles with radii between 10 and 20 nm at a pH‐value below 5, where the carboxylic acid groups are in the protonated state. The block copolymer micelles show a strong increase of the hydrodynamic radius with increasing pH‐value, due to the repulsion among the formed carboxylate anions resulting in a stretching of the polymer chains. In this state, the micelles exhibit responsive behavior to ionic strength where a contraction of the micelles is observed as the carboxylate charges are balanced by sodium ions, whereas no changes of the hydrodynamic radius on addition of salt are observed at low pH. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 1178–1191, 2009

Phase Behavior of Polyelectrolyte Block Copolymers in Mixed Solvents

We have studied the phase behavior of the poly(n-butyl acrylate)-b-poly(acrylic acid) block copolymer in a mixture of two miscible solvents, water and tetrahydrofuran (THF). The techniques used to examine the different polymers, structures and phases formed in mixed solvents were static and dynamic light scattering, small-angle neutron scattering, nuclear magnetic resonance and fluorescence microscopy. By lowering the water/THF mixing ratio X, the sequence unimers, micron-sized droplets, polymeric micelles was observed. The transition between unimers and the micron-sized droplets occurred at X = 0.75, whereas the microstructuration into core-shell polymeric micelles was effective below X = 0.4. At intermediate mixing ratios, a coexistence between the micron-sized droplets and the polymeric micelles was observed. Combining the different aforementioned techniques, it was concluded that the droplet dispersion resulted from a solvent partitioning that was induced by the hydrophobic blocks. Comparison of poly(n-butyl acrylate) homopolymers and poly(n-butyl acrylate)-b-poly(acrylic acid) block copolymers suggested that the droplets were rich in THF and concentrated in copolymers and that they were stabilized by the hydrophilic poly(acrylic acid) moieties.

Hydrogel-based sensor for a rheochemical characterization of solutions

We propose a new type of on-line analytics system for biomedical and environmental monitoring. In order to provide the specific analyte detection, a chemical sensor with a functionalised hydrogel coating has been integrated together with a viscosity sensor in a miniaturized biocompatible rheochemical microsystem. The sensor has been calibrated and tested in aqueous solutions of alcohol and salts of different concentration. The selective sensitivity of the polyelectrolyte block-copolymer coating to toxic transition-metal ions has been demonstrated.

Electrostatic Self-Assembly of Neutral and Polyelectrolyte Block Copolymers and Oppositely Charged Surfactant

We investigated the phase behavior and the microscopic structure of the colloidal complexes constituted from neutral/polyelectrolyte diblock copolymers and oppositely charged surfactant by dynamic light scattering (DLS) and small-angle neutron scattering (SANS). The neutral block is poly(N-isopropylacrylamide) (PNIPAM), and the polyelectrolyte block is negatively charged poly(acrylic acid) (PAA). In aqueous solution with neutral pH, PAA behaves as a weak polyelectrolyte, whereas PNIPAM is neutral and in good-solvent condition at ambient temperature, but in poor-solvent condition above approximately 32 degrees C. This block copolymer, PNIPAM-b-PAA with a narrow polydispersity, is studied in aqueous solution with an anionic surfactant, dodecyltrimethylammonium bromide (DTAB). For a low surfactant-to-polymer charge ratio Z lower than the critical value ZC, the colloidal complexes are single DTAB micelles dressed by a few PNIPAM-b-PAA. Above ZC, the colloidal complexes form a core-shell microstructure. The core of the complex consists of densely packed DTA+ micelles, most likely connected between them by PAA blocks. The intermicellar distance of the DTA+ micelles is approximately 39 A, which is independent of the charge ratio Z as well as the temperature. The corona of the complex is constituted from the thermosensitive PNIPAM. At lower temperature the macroscopic phase separation is hindered by the swollen PNIPAM chains. Above the critical temperature TC, the PNIPAM corona collapses leading to hydrophobic aggregates of the colloidal complexes.

Stimuli-Responsive Polyelectrolyte Block Copolymer Brushes Synthesized from the Si Wafer via Atom-Transfer Radical Polymerization

Surface-tethered oppositely charged weak polyelectrolyte block copolymer brushes composed of poly(2-vinyl pyridine) (P2VP) and poly(acrylic acid) (PAA) were grown from the Si wafer by atom-transfer radical polymerization. The P2VP-b-PAA brushes were prepared through hydrolysis of the second PtBA block to the corresponding acrylic acid. The P2VP-b-PAA brushes with different PAA block length were obtained. The P2VP-b-PAA brushes revealed a unique reversible wetting behavior with pH. The difference between the solubility parameters for P2VP and PAA, the changes of surface chemical composition and surface roughness, and the reversible wetting behavior illustrated that the surface rearrangement occurred during treatment of the P2VP-b-PAA brushes by aqueous solution with different pH value. The reversible properties of the P2VP-b-PAA brushes can be used to regulate the adsorption of the sulfonated PS nanoparticles.

Effect of Solvent Concentration to the Preparation of Polystyrene Nanoparticles Using Polyelectrolyte Block Copolymer

ABSTRACTParticles of sizes within the nano region have attracted many applications in different fields of science. In this study, the self assembly property in a selective solvent of block copolymers has been used for the preparation of polystyrene nanospheres. Sulfonated Styrene-Butadiene-Styrene (SSBS) tri block copolymer was used as a polymeric surfactant for synthesis of uniformly sized polystyrene nanoparticles using emulsion polymerization. The effects of initiator, monomer and block copolymer concentration to the molecular weight distribution and size distribution were investigated. Uniformly sized nanoparticles with a polydispersity index of 1.004 and diameter of 112.9nm was verified by Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM), respectively. Using a mixed continuous phase solution of water and methanol, it was found out that the particle size decreased relative to the increase of methanol added to the reaction solution. Associating behavior of the polyelectrolyte block copolymer in the binary solvent environment regarding size of micelle formed was reflected on the properties of the nanospheres. Nanoparticles prepared with greater methanol concentration were observed to be less than 100 nm. Size distribution was also observed to be narrower in proportion to MeOH concentration.