Charged Block Copolymers Research Articles

Self-assembled polyion complex micelles for sustained release of hydrophilic drug

Graft copolymer polyethylenimine–graft–poly(N-vinylpyrrolidone) (PEI-g-PVP) was prepared by coupling mono carboxyl-terminated PVP (PVP–COOH) with PEI using N,N′-dicyclohexylcarbodiimide (DCC) and N-hydroxysuccinimide (NHS) as coupling agents. In aqueous medium, PVP–g–PEI can self-assemble into stable polyion complex micelles with an oppositely charged block copolymer, poly(N-vinylpyrrolidone)–block–poly(2-acrylamido-2-methyl-1-propanesulphonic acid) (PVP-b-PAMPS). Transmission electron microscopy images showed that these micelles were regularly spherical in shape. The micelle size determined by size analysis was around 142 nm. To estimate their feasibility as vehicles for drugs, the model drug folic acid (FA) was incorporated into the cores of the micelles via electrostatic interactions. In vitro release test of FA showed that the drug-release rates are dependent on the pH value of the release media. Based on these results, we can conclude that the polyion complex micelles prepared from the PEI-g-PVP/PVP-b-PAMPS copolymers have great potential as drug delivery nanocarriers.

Morphological Manipulation of Ionic Block Copolymer Micelles Using an Electric Field

We present an electric-field-triggered sphere-to-cylinder transition of negatively charged block copolymer micelles with a radically low electric field of 30 V/cm. The system investigated is dilute solutions of strong polyelectrolyte containing ionic-b-neutral block copolymers (i.e., poly(styrenesulfonate-b-methylbutylene)). We have carried out in situ small-angle X-ray scattering experiments equipped with a dc power supply, combined with electron microscopy and atomic force microscopy. The application of small electrical fields across the solutions of spherical micelles results in the transient morphology of interconnected spheres, which are eventually transformed into a cylindrical shape with time. The E-field-induced cylindrical micelles revert to spherical micelles when the E field is switched off.

Facile fabrication of colloidal particles based on the electrostatic aggregation of block copolymer micelles

Block copolymer assembled colloidal particles were successfully prepared through electrostatic interactions between cationic polystyrene- block-poly(4-vinylpyridine) (PS- b-P4VP) and anionic polystyrene- block-poly(acrylic acid) (PS- b-PAA) in a one-pot process. The colloidal particles were prepared by simple mixing of complementary charged block copolymer micelle aqueous solution. This process presents the possibility of very simple and versatile method of mass production of BCM based colloidal particles. Both hairy and crew-cut types of block copolymer micelles (BCMs) showed different electrostatic assembly tendencies as confirmed by Field emission scanning electron microscopy (FE-SEM). These phenomena are mainly caused by the different degrees of electrostatic interdigitation and entanglement between the protonated and deprotonated corona block regions of the micelles.

Synthesis and characterization of polyion complex micelles and their controlled release of folic acid

Stable and narrow distribution polyion complex micelles (PICMs) were prepared in an aqueous milieu through electrostatic interaction between a pair of oppositely charged block copolymers poly( N-vinylpyrrolidone)-block-poly(2-acrylamido-2-methyl-1-propanesulfonic acid) (PVP-b-PAMPS) and monomethoxy poly(ethylene glycol)-block-poly(4-vinyl pyridine) (PEG-b-P4VP). The critical aggregate concentration (CAC), hydrodynamic size, and surface morphology of the prepared PICMs were characterized by fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM), respectively. The resulting CAC and the average diameter of the PICMs were about 43 mg/L and 121 nm, indicating high structural stability of micelles and a size favorable for delivery of drug. In addition, the PICMs exhibited good biocompatibility using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay with human embryonic kidney (HEK293) cells. All of these features are quite feasible for utilizing the PICMs as a novel intelligent drug delivery system. In order to assess its application in the biomedical area, the model drug folic acid (FA) was loaded into the micelles and the in vitro drug release behavior was investigated. We found that by manipulating the pH value and salt concentration of the release solution, it was possible to control the release rate of FA.

Self-assembled Polyion Complex Micelles based on PVP-b-PAMPS and PVP-b-PDMAEMA for Drug Delivery

The double hydrophilic block copolymer, poly(N-vinylpyrrolidone)-block-poly(2-acrylamido-2-methyl-1-propanesulfonic acid), was synthesized by reversible addition-fragmentation chain transfer RAFT polymerization. Gel permeation chromatography, 1H-NMR, and FTIR were used to determine the structure and composition. In aqueous media, this block copolymer spontaneously forms polyion complex (PIC) micelles with an oppositely charged block copolymer, poly(N-vinylpyrrolidone)-block-poly(N, N-dimethylaminoethyl methacrylate). Dynamic light scattering and transmission electron micrograph showed that the micelles were <200 nm in diameter and had a narrow single distribution. The release profiles of folic acid, incorporated into the micelles, showed remarkable pH responsive behavior. The PIC micelles exhibited good biocompatibility based on MTT assay with human embryonic kidney (HEK293) cells. These PIC micelles have the potential as pH-sensitive carriers for drug delivery.

Controllable stacked disk morphologies of charged diblock copolymers

Monte Carlo simulations are used to demonstrate the controlled stacking of charged block copolymer disk morphologies that can be obtained under certain thermodynamic conditions. We examine a partially charged block copolymer where 75% of the blocks are neutral and 25% of the blocks are charged. The presence of strong electrostatic interactions promotes charge agglomeration thereby changing morphologies in these systems. This study relates different thermodynamic quantities for which disk-like stackings can be obtained. The long-range order can be sustained even if hydrophobicity is increased albeit with lower dimensional structures. Our simulation results agree very well with recent experiments and are consistent with theoretical observations of counterion adsorption on flexible polyelectrolytes.

Tunable morphologies from charged block copolymers

The bulk morphologies formed by a new class of charged block copolymers, 75 vol % fluorinated polyisoprene (FPI) – 25 vol% sulfonated polystyrene (PSS) with 50% sulfonation, are characterized, and the fundamental underlying forces that promote the self-assembly processes are elucidated. The results show how the bulk morphologies are substantially different from their uncharged diblock counterparts (PS-PI) and also how morphology can be tuned with volume fraction of the charged block and the casting solvent. A physical understanding based on the underlying strong electrostatic interactions between the charged block and counterions is obtained using Monte Carlo (MC) and Molecular Dynamics (MD) simulations. The 75/25 FPI-PSS shows hexagonal morphologies with the minority blocks (PSS) forming the continuous phase due to charge percolation and the FPI blocks arranged in hexagonal cylinders. Some long-range order can be sustained even if lipophobicity is increased (addition of water), albeit with lower dimensional structures. However, thermal annealing provides sufficient energy to disrupt the percolated charges and promotes aggregation of ionic sites which leads to a disordered system. Diverse and atypical morphologies are readily accessible by simply changing the number distribution of the charges on the PSS block.

Interpolyelectrolyte Complexes of Dynamic Multicompartment Micelles

Dynamic core-shell-shell-corona micelles are formed between two oppositely charged block copolymer systems. Preformed polybutadiene-block-poly(N-methyl-2-vinylpyridinium)-block-poly(methacrylic acid) (PB-P2VPq-PMAA) block terpolymer micelles with a soft polybutadiene core, an interpolyelectrolyte complex (IPEC) shell made out of poly(N-methyl-2-vinylpyridinium) and poly(methacrylic acid), and a negatively charged PMAA corona were mixed in different ratios at high pH with positively charged poly(N-methyl-2-vinylpyridinium)-block-poly(ethylene oxide) (P2VPq-PEO) diblock copolymers. Under these conditions, mixing results in the formation of a second IPEC shell onto the PB-P2VPq-PMAA precursor micelles, surrounded by a PEO corona. The resulting multicompartmented IPECs exhibit dynamic behavior, highlighted by a structural relaxation within a period of 10 days, investigated by dynamic light scattering (DLS), cryogenic transmission electron microscopy (cryo-TEM), and scanning force microscopy (SFM). After a short mixing time of 1 h, the IPECs exhibit a star-shaped structure, whereas after 10 days, spherical core-shell-shell-corona objects could be observed. To further increase complexity and versatility of the presented systems, the in situ formation of gold nanoparticles (Au NPs) in both the precursor micelles and the equilibrated IPEC was tested. For the PB-P2VPq-PMAA micelles, NP formation resulted in narrowly distributed Au NPs located within the PMAA shell, whereas for the core-shell-shell-corona IPEC, the Au NPs were confined within the IPEC shell and shielded from the outside through the PEO corona.

Synthesis of Oppositely Charged Block Copolymers of Poly(ethylene glycol) via Reversible Addition−Fragmentation Chain Transfer Radical Polymerization and Characterization of Their Polyion Complex Micelles in Water

Diblock copolymers consisting of a water-soluble nonionic block and either an anionic or cationic block were prepared from sodium 2-(acrylamido)-2-methylpropanesulfonate (AMPS) or (3-(methacryloylamino)propyl)trimethylammonium chloride (MAPTAC) via reversible addition−fragmentation chain transfer (RAFT)-controlled radical polymerization using poly(ethylene glycol) (PEG)-based chain transfer agent (PEG-CTA) in water. The RAFT polymerization proceeded in a living fashion, as suggested by the observation that the number-average molecular weight (Mn) increased linearly with the monomer conversion (up to conversions of 30% for MAPTAC and 50% for AMPS), whereas the polydispersity (Mw/Mn) remained nearly constant (Mw/Mn < 1.05 for MAPTAC and <1.2 for AMPS) independent of the conversion. The mixing of aqueous solutions of the oppositely charged diblock copolymers, PEG-b-PAMPS and PEG-b-PMAPTAC, led to the spontaneous formation of polyion complex (PIC) micelles. The PIC micelles were characterized by 1H NMR spin−spin relaxation time, static light scattering (SLS), dynamic light scattering (DLS), and scanning electron microscopy (SEM) techniques. The hydrodynamic size of the micelle depended on the mixing ratio of PEG-b-PAMPS and PEG-b-PMAPTAC with the size maximizing at the mixing ratio of stoichiometric charge neutralization. The mixing of the oppositely charged diblock copolymers with shorter charged blocks formed a core−shell PIC micelle. In contrast, a complicated aggregate was formed from a pair of longer blocks. The exact structure of the aggregate is still an open question, but it is speculated to be a multicore intermicellar aggregate on the basis of various characterization data.

Synthesis and association properties of thermoresponsive and permanently cationic charged block copolymers

Atom transfer radical polymerization (ATRP) was used to prepare thermosensitive cationic block copolymers of (3-acrylamidopropyl)-trimethylammonium chloride (AMPTMA) and N-isopropylacrylamide (NIPAAM) with different block lengths. By using ethyl-2-chloropropionate (ECP) as initiator and CuCl/CuCl2/tris(2-dimethylaminoethyl)amine (Me6TREN) catalytic system in DMF:water 50:50 (v/v) mixtures at 20°C the polymerization was controlled. The association properties in NaCl aqueous solution were studied as a function of temperature and polymer concentration by dynamic light scattering, NMR spectroscopy, fluorescence spectroscopy and energy filtered-transmission electron microscopy. The block copolymers formed micellar aggregates above the lower critical solution temperature (LCST) of pNIPAAM. The LCST is strongly influenced by the relative length of the two blocks and is significantly higher than that of pure pNIPAAM. The size of core and shell of the micelles is discussed in terms of block copolymer composition.

Solid-Supported Block Copolymer Membranes through Interfacial Adsorption of Charged Block Copolymer Vesicles

The properties of amphiphilic block copolymer membranes can be tailored within a wide range of physical parameters. This makes them promising candidates for the development of new (bio)sensors based on solid-supported biomimetic membranes. Here we investigated the interfacial adsorption of polyelectrolyte vesicles on three different model substrates to find the optimum conditions for formation of planar membranes. The polymer vesicles were made from amphiphilic ABA triblock copolymers with short, positively charged poly(2,2-dimethylaminoethyl methacrylate) (PDMAEMA) end blocks and a hydrophobic poly( n-butyl methacrylate) (PBMA) middle block. We observed reorganization of the amphiphilic copolymer chains from vesicular structures into a 1.5+/-0.04 nm thick layer on the hydrophobic HOPG surface. However, this film starts disrupting and dewetting upon drying. In contrast, adsorption of the vesicles on the negatively charged SiO2 and mica substrates induced vesicle fusion and formation of planar, supported block copolymer films. This process seems to be controlled by the surface charge density of the substrate and concentration of the block copolymers in solution. The thickness of the copolymer membrane on mica was comparable to the thickness of phospholipid bilayers.

Field‐theoretic simulations of polyelectrolyte complexation

Field‐theoretic simulations of polyelectrolyte complexation

Chemical analysis and aqueous solution properties of charged amphiphilic block copolymers PBA- b-PAA synthesized by MADIX ®

We have linked the structural and dynamic properties in aqueous solution of amphiphilic charged diblock copolymers poly(butyl acrylate)- b-poly(acrylic acid), PBA- b-PAA, synthesized by controlled radical polymerization, with the physico-chemical characteristics of the samples. Despite product imperfections, the samples self-assemble in melt and aqueous solutions as predicted by monodisperse microphase separation theory. However, the PBA core are abnormally large; the swelling of PBA cores is not due to AA (the Flory parameter χ PBA / PAA , determined at 0.25, means strong segregation), but to h-PBA homopolymers (content determined by liquid chromatography at the point of exclusion and adsorption transition, LC-PEAT). Beside the dominant population of micelles detected by scattering experiments, capillary electrophoresis CE analysis permitted detection of two other populations, one of h-PAA, and the other of free PBA- b-PAA chains, that have very short PBA blocks and never self-assemble. Despite the presence of these free unimers, the self-assembly in solution was found out of equilibrium: the aggregation state is history dependant and no unimer exchange between micelles occurs over months (time-evolution SANS). The high PBA/water interfacial tension, measured at 20 mN/m, prohibits unimer exchange between micelles. PBA- b-PAA solution systems are neither at thermal equilibrium nor completely frozen systems: internal fractionation of individual aggregates can occur.

Supramolecular Assembly of Photofunctional Dendrimers for Biomedical Nano-Devices

Recently, dendrimers are attracting much attention for their development as biomedical nano-devices. In the present paper, we introduce dendrimer photosensitizers, composed of a focal photosensitizing unit surrounded by poly(benzyl ether) dendritic wedges, for photodynamic therapy (PDT). Ionic dendritic porphyrins (DPs) formed supramolecular polyion complex (PIC) micelles through the electrostatic interaction with oppositely charged block copolymers, and showed no self-quenching effect of the focal photosensitizing unit due to the large dendritic wedges. The DP-loaded PIC micelles showed selective accumulation to the ophthalmic neovascular lesion and effective photodynamic effect. For the effective light delivery, dendrimer phthalocyanine (DPc) has also been developed and examined for its photodynamic effect.

Controlled Stacking of Charged Block Copolymer Micelles

Using poly(acrylic acid)-b-poly(methyl acrylate)-b-polystyrene (PAA-b-PMA-b-PS) triblock copolymers or a mixture of different molecular weight PAA-b-PS diblock copolymers, stacks of polymeric micellar assemblies, such as disks and Y-shaped cylinders, were formed through intermicellar interactions. Whereas micelles hierarchically stacked together, micellar interactions within the stack defined a uniform micelle geometry and size for up to micrometers in length. The kinetic pathway dependence and stability of the stacked assemblies were studied, and possible intermicellar interactions between micelles within the stacks are proposed.

Layer‐by‐Layer Formation of Smart Particle Coatings Using Oppositely Charged Block Copolymer Micelles

Multilayer coatings of colloidal particle substrates (see figure) formed entirely from block copolymer micelles are demonstrated. Such multilayer coatings provide a highly functional organized coating that may have application across a wide range of technology areas, and provide a coating mechanism for controlled loading and release of active materials.

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.

Semipermeable Polymer Vesicle (PICsome) Self-Assembled in Aqueous Medium from a Pair of Oppositely Charged Block Copolymers: Physiologically Stable Micro-/Nanocontainers of Water-Soluble Macromolecules

A new entity of polymer vesicle with a polyion complex (PIC) membrane, a PICsome, was prepared by simple mixing of a pair of oppositely charged block copolymers, composed of biocompatible PEG and poly(amino acid)s, in an aqueous medium. Flow particle image analysis revealed the formation of spherical particles with a size range up to 10 mum. Observation by dark-field and confocal laser scanning microscopes clearly confirmed that the PICsome has a hollow structure with an inner-water phase, in which FITC-dextran emitting green fluorescence was successfully encapsulated simply by the simultaneous mixing with the block copolymers. Confocal laser scanning microscopic observation and spectral analysis revealed the smooth penetration of a low molecular weight fluorescent dye (TRITC; MW = 443.5) emitting red fluorescence into the FITC-dextran encapsulated PICsome to give the PICsome image with a merged color of yellows, indicating the semipermeable nature of the PICsome membrane. The PICsomes showed appreciable physiological stability even in the presence of serum proteins, suggesting their feasibility in biomedical fields such as carriers of therapeutic compounds and compartments for diagnostic enzymes.

Hydrophobic-Charged Block Copolymer Micelles Induced by Oppositely Charged Surfaces: Salt and pH Dependence

We analyze the possibility of inducing surface micellization of hydrophobic and charged block copolymers by an oppositely charged surface using a two-state model with lateral correlations among adsorbed chains. The electrostatic attraction between the charged block and the charged surface induces diblock copolymer micellization on the surface at copolymer concentrations well below the critical micelle concentration in the bulk. We study systems with strong charge groups which have fixed charge densities and systems with weak charge groups which have solution-dependent degrees of ionizations. We analyze the effects of salt concentration, solution pH, surface charge density, polyelectrolyte block line charge density, surface tension of the hydrophobic block, and polymerization degrees of the blocks on the induced micellization. It is found that at low salt concentrations the number of chains per micelle does not significantly depend on the degree of polymerization of the charged block. The addition of salt increases the critical surface micelle concentration when the electrostatic attraction between the charged blocks and the surface dominates the electrostatic repulsion among adsorbed chains. At low salt concentration, the excluded volume has a minor effect on surface induced micelles for systems with strong charge groups. However, in systems with weak charge groups, where both the surface and block degrees of ionizations are determined self-consistently as a function of pH, the excluded volume decreases the pH effect on the polyelectrolyte degree of ionization at surfaces.

Actomyosin-Driven Motility on Patterned Polyelectrolyte Mono- and Multilayers

Positive polyelectrolytes were investigated as new surface coatings for promoting in vitro actomyosin motility. Two surface arrangements were studied: a monolayer of the polyelectrolyte PAH, poly(allylamine hydrochloride), and multilayers consisting of 11−41 layers of alternating polypositive PAH/polynegative PSS (polystyrene sulfonate) electrolytes. For in vitro motility assays, rabbit skeletal muscle heavy meromyosin (HMM) was applied to the PAH surface of the polyelectrolyte mono/multilayer. Myosin-driven motion of actin filaments labeled with rhodamine−phalloidin was recorded at 30 °C using epifluorescence microscopy. Actin filaments were found to have a mean speed of 2.9 ± 0.08 μm/sec on the multilayer surface compared to 2.5 ± 0.06 μm/sec on the monolayer surface. Average filament length and speed increased when nonionic surfactant was added to HMM and ionic strength of the motility buffer increased, respectively. Microcontact printing with a water-insoluble charged block copolymer on PAH produced ...