Core Shell Corona Micelles Research Articles

Polymerization-Induced Hierarchical Self-Assembly: From Monomer to Complex Colloidal Molecules and Beyond.

The nanoscale hierarchical design that draws inspiration from nature's biomaterials allows the enhancement of material performance and enables multifarious applications. Self-assembly of block copolymers represents one of these artificial techniques that provide an elegant bottom-up strategy for the synthesis of soft colloidal hierarchies. Fast-growing polymerization-induced self-assembly (PISA) renders a one-step process for the polymer synthesis and in situ self-assembly at high concentrations. Nevertheless, it is exceedingly challenging for the fabrication of hierarchical colloids via aqueous PISA, simply because most monomers produce kinetically trapped spheres except for a few PISA-suitable monomers. We demonstrate here a sequential one-pot synthesis of hierarchically self-assembled polymer colloids with diverse morphologies via aqueous PISA that overcomes the limitation. Complex formation of water-immiscible monomers with cyclodextrin via "host-guest" inclusion, followed by sequential aqueous polymerization, provides a linear triblock terpolymer that can in situ self-assemble into hierarchical nanostructures. To access polymer colloids with different morphologies, three types of linear triblock terpolymers were synthesized through this methodology, which allows the preparation of AXn-type colloidal molecules (CMs), core-shell-corona micelles, and raspberry-like nanoparticles. Furthermore, the phase separations between polymer blocks in nanostructures were revealed by transmission electron microscopy and atomic force microscopy-infrared spectroscopy. The proposed mechanism explained how the interfacial tensions and glass transition temperatures of the core-forming blocks affect the morphologies. Overall, this study provides a scalable method of the production of CMs and other hierarchical structures. It can be applied to different block copolymer formulations to enrich the complexity of morphology and enable diverse functions of nano-objects.

Europium based coordination polyelectrolytes enable core-shell-corona micelles as luminescent probes.

Core-shell-corona (CSC) micelles have multiple layers, which can serve as separate compartments. This property allows them to combine multiple functionalities in a single nanoparticle, with obvious application potential. Here, we propose a new type of CSC micelles with an apolar core and a polyelectrolyte complex shell incorporating coordination polymers. We obtain these particles by using a poly(styrene)-b-poly(vinyl pyridine)-b-poly(ethylene oxide) (PS-b-PVP-b-PEO) triblock copolymer with quaternized PVP blocks. This polymer leads to well-defined CSC micelles with a cationic shell, which allows us to entrap anionic coordination polymers without disturbing the micellar structure. Useful properties can be imported in this way, e.g., europium (Eu)-based coordination polymers endow the CSC micelles with strong luminescence. Moreover, copper ions (Cu2+) can quench the luminescence because they disturb the Eu-ligand coordination. Upon adding sulfide ions (S2-), copper ions precipitate as CuS and the Eu-ligand bond as well as the corresponding luminescence are restored. This effect is highly specific for Cu2+ and S2-: other cations or anions hardly interfere with this "on-off-on" luminescence response towards Cu2+ and S2-, demonstrating the selectivity of these CSC micelles as detectors of copper and sulfide ions.

Computer simulation study on the self-assembly of tethered nanoparticles with tunable shapes.

We built a tethered nanoparticle (TNP) model that is composed of a nanoparticle with a hydrophobic tethered polymer chain. The shape of the nanoparticle can be tuned from a pure rigid cube to a soft sphere, mimicking the increase of grafting density on the nanocube surfaces. With this model, we study the self-assembly of TNPs in dilute solution using a dissipative particle dynamics simulation technique, and especially focus on the influence of particle shape, tethered chain length, and grafting density on the self-assembly structures. Some intriguing aggregates such as spherical micelles, pearl-necklace-like structures, cubic columnar structures, handshake structures, core–shell–corona micelles, and four-patch micelles have been observed when varying the interactions between cubes and solvents and the lengths of tethered chain. Modifying the nanocube surface with some hydrophilic grafted chains helps the TNPs form small micelles. Increased steric repulsion due to chain overlapping at larger grafting densities results in shape transformation of the nanoparticle from a rigid cube to a soft sphere. In these cases, the self-assembled structures are characterized by the packing of nanoparticles on the micelle surface, and the typical packing mode turns from rectangular (typical for cubes) to hexagonal (typical for spheres).

Core-Shell-Corona Micelles from a Polyether-Based Triblock Terpolymer: Investigation of the pH-Dependent Micellar Structure.

Core-shell-corona micelles featuring a pH-responsive shell have been characterized in dilute aqueous solution at different pH values (4-8) by using dynamic light scattering (DLS), field-flow fractionation coupled with multiangle light scattering detector (FFF-MALS), steady-state fluorescence, small-angle X-ray scattering (SAXS), and cryogenic transmission electron microscopy (cryo-TEM). The micelles are formed by self-assembly of a polyether-based triblock terpolymer consisting of a hydrophobic poly( tert-butyl glycidyl ether) block (P tBGE), a pH-responsive modified poly(allyl glycidyl ether) segment (PAGECOOH), and a neutral hydrophilic poly(ethylene oxide) block (PEO). Because of the side-chain carboxylic acids in the middle block, the micellar structure and size depends on the solution pH. Hereby, we show that an increase in pH induces a decrease in the aggregation number ( Nagg). In addition, the combination of the above measurements revealed an unexpected morphological change from spherical to ellipsoidal micelles by increasing pH.

Micellization of pH‐sensitive poly(butadiene)‐block‐poly(2 vinylpyridine)‐block‐poly(ethylene oxide) triblock copolymers: Complex formation with anionic surfactants

ABSTRACTThe micellization of three tailor‐made triblock copolymers, such as PB100–P2VP100–PEO104, PB185–P2VP108–PEO154, and PB37–P2VP115–PEO241, having similar total molecular weights and constant poly(2‐vinylpyridine) (P2VP) sequence lengths, was investigated as a function of pH and sodium dodecyl sulfate (SDS) concentration. At pH 7 the formation of intermicellar aggregates was observed, especially for copolymers of low poly(ethylene oxide) (PEO) content. A pH decrease from 7 to 3 leads to a particle size increase due to the electrostatic repulsion of the protonated P2VP chains. The influence of the PEO sequence length was also observed for zeta potential values. At pH 3, in the absence of SDS, core–shell–corona micelles are formed whereas in the presence of small amount of SDS (degree of neutralization DN = 0%–50%), a complex is formed between SDS and the protonated P2VP which leads to the shrinkage of the shell and thus to a decrease of the micellar sizes. For higher DN values, the micellar sizes increase due to the formation of large agglomerates and a transition occurs from a monomodal to a bimodal size distribution. Furthermore, it turned out that secondary aggregation, such as intermicellar aggregation, can completely be avoided if the degree of polymerization (DPn) of the water‐soluble block is significantly higher than the DPn of the water‐insoluble sequence. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45313.

Synthesis of sharply thermo and PH responsive PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA by RAFT radical polymerization and its schizophrenic micellization in aqueous solutions

Sharply thermo- and pH-responsive pentablock terpolymer with a core-shell-corona structure was prepared by RAFT polymerization of N-isopropylacrylamide and methacrylic acid monomers using PEG-based benzoate-type of RAFT agent. The PEG-based RAFT agent could be easily synthesized by dihydroxyl-capped PEG with 4-cyano-4-(thiobenzoyl) sulfanylpentanoic acids, using esterification reaction. This pentablock terpolymer was characterized by 1H NMR, FT-IR, and GPC. The PDI was obtained by GPC, indicating that the molecular weight distribution was narrow and the polymerization was well controlled. The thermo- and pH-responsive micellization of the pentablock terpolymer in aqueous solution was investigated using fluorescence spectroscopy technique, UV–vis transmittance, and TEM. The LCST of pentablock terpolymer increased (over 50 °C) compared to the NIPAM homopolymer (~32 °C), due to the incorporation of the hydrophilic PEG and PMA blocks in pentablock terpolymer (PNIPAM block as the core, PEG the block and the hydrophilic PMA block as the shell and the corona). Also, pH-dependent phase transition behavior shows at a pH value of about ~5.8, according to pKa of MAA. Thus, in acidic solution at room temperature, the pentablock terpolymer self-assembled to form core–shell–corona micelles, with the hydrophobic PMA block as the core, the PNIPAM block and the hydrophilic PEG block as the shell and the corona, respectively.

Reduction-responsive core-shell-corona micelles based on triblock copolymers: novel synthetic strategy, characterization, and application as a tumor microenvironment-responsive drug delivery system.

A facile and effective approach was established for fabricating core-shell-corona micelles by self-assembly of poly(ethylene glycol)-b-poly(acrylic acid-co-tert-butyl acrylate)-poly(ε-caprolactone) (PEG43-b-P(AA30-co-tBA18)-b-PCL53) triblock copolymer, synthesized via a combination of ring-opening polymerization (ROP), atom transfer radical polymerization (ATRP), click chemistry, and hydrolyzation. The prenanovehicles with three different hydrolysis degrees from PEG43-b-PtBA48-b-PCL53 were developed to evaluate the drug loading capacity (DLC) and drug encapsulation efficiency (DEE). After cross-linking with a disulfide bond to regulate the drug release kinetics, the spherical core-shell-corona micelles with average diameter of 52 ± 4 nm were obtained in aqueous solution. The reduction-responsive cross-linked micelles showed a slow sustained release in normal physiological conditions and a rapid release upon exposure to simulated tumor intracellular conditions. In addition, the cytotoxic analysis and HepG2 cell growth inhibition assays demonstrated their remarkable biocompatibility and similar excellent anticancer activity as the free doxorubicin (DOX), which has also been revealed by the confocal laser scanning microscope (CLSM) analysis. So the reduction-sensitive core-shell-corona micelles are expected to be promising tumor microenvironment-responsive nanovehicles for hydrophobic drugs by glutathione (GSH) triggering.

Self-assembly behavior of pH- and thermo-responsive hydrophilic ABCBA-type pentablock copolymers synthesized by consecutive RAFT polymerization

A multi-responsive hydrophilic ABCBA-type pentablock copolymer, consisting of poly(ethylene glycol), poly(N-isopropylacrylamide), and poly(2-(diethylamino)ethyl methacrylate), PDEA-b-PNIPAM-b-PEG-b-PNIPAM-b-PDEA, was synthesized by consecutive reversible addition–fragmentation chain transfer (RAFT) polymerization. The polymerization showed all of the expected features of living radical polymerization and allowed the synthesis of copolymers with controlled lengths of the PNIPAM and PDEA blocks. Due to the multi-component and multi-functional nature of the pentablock copolymer, the solution properties can be manipulated by the changing of parameters such as temperature, pH etc. For example, the copolymer could be dissolved in acidic aqueous solution at room temperature, since the pH was below the pKa of the PDEA block, and the temperature was below the lower critical solution temperature (LCST) of the PNIPAM block. While in alkaline solution at room temperature, the copolymer self-assembled into core–shell–corona micelles, with the hydrophobic PDEA block as the core, the thermoresponsive PNIPAM block as the shell and the hydrophilic PEG block as the corona. At elevated temperatures in acidic media, the copolymer self-assembled into PNIPAM-core micelles with mixed hydrophilic PEG and pH-responsive PDEA coronas. Moreover, the self-assembly behavior of the pentablock copolymers in aqueous solution was investigated by varying the length of PDEA blocks.

Novel shell-cross-linked micelles with detachable PEG corona for glutathione-mediated intracellular drug delivery

A series of novel disulfide-containing triblock copolymers, poly(ethylene glycol)-b-poly(L-lysine)-b-poly(rac-leucine) (PEG-SS-PLys-PLeu), were prepared. In an aqueous solution, the copolymers could self-assemble to form core–shell-corona micelles with a disulfide-linked detachable PEG corona, since the PLys middle shell with primary amine groups was linked by a disulfide-containing cross-linker. The morphology and stability of self-assembled micelles were characterized by TEM, DLS and SEM. In the intracellular environment, the micelles underwent destruction of the cross-linked shell with detachment of the PEG corona due to the cleavage of disulfide bonds, followed by the collapse of micelles. The in vitro drug release in response to GSH was further studied. Interestingly, it was found that the micelles not only exhibited reduced drug loss in extracellular environments, but also drastically accelerated drug release at the cytoplasmic GSH level, leading to enhanced growth inhibition of HeLa cells. The glutathione-responsive micelles might have great potential in intracellular drug delivery.

Cascade Molecule–Particle–Molecule Self-Assemblies for Fabricating Narrowly Size-Distributed Polymeric Superparticles with a Bicontinuous Nanostructure

Broader developments of nanoscience and nanotechnology require complexly but regularly structured nanoparticles whose fabrications in turn pose a great challenge to nanoscience and nanotechnology. In this communication, we report a new and robust method with a clear mechanism for fabricating narrowly size-distributed superparticles with a bicontinuous inner structure. The processes for the fabrication include: molecular self-assembly of a triblock copolymer in its selective solvent into the core-shell-corona micelles, the self-limited aggregation of the micelles (particles) into narrowly size-distributed superparticles constructed by the integrated micelles, and the final molecular self-assembly confined within the superparticles into cylinders that are crowded and interconnected to form the bicontinuous nanostructure; the molecular self-assembly into the micelles, the self-limited aggregation of the particles (i.e., the micelles), and the further molecular self-assembly within the superparticles occurred in a cascade manner.

Synthesis, self-assembly, and pH-responsive behavior of (photo-crosslinked) star amphiphilic triblock copolymer

Conventional polymeric micelles employed as drug carriers suffer from the drawback of disaggregation when diluted into body fluids, giving rise to premature release of drugs. In this work, cinnamate was chosen as a crosslinker to overcome this issue and regulate pH response. A series of photo-crosslinkable star amphiphilic triblock copolymers, star poly(ε-caprolactone)-b-poly(2-cinnamoyloxyethyl methacrylate)-b-poly(2-(dimethylamino)ethyl methacrylate) (SPCL-b-PCEMA-b-PDMAEMA), were prepared by combination of stepwise reversible addition-fragment chain transfer (RAFT) polymerization and carbodiimide-mediated coupling reaction. These star amphiphilic copolymers could self-assemble into core–shell-corona micelles. Facile photo crosslinking of the micelles was carried out via UV irradiation. The crosslinked micelles showed an improved stability determined by critical micelle concentration (CMC). The degree of photo crosslinking was easily regulated by tuning UV irradiation time, and the hydrodynamic diameters (Dh) decreased with increasing degree of photo crosslinking. The pH responses of micelles were investigated by dynamic light scattering (DLS), indicating pH-induced swelling-shrinking behavior. For photo-crosslinked micelle, its capability of swelling-shrinking weakened with increasing crosslinking degree, suggesting that pH response was controlled by crosslinking density. This novel photo-crosslinked micelle system with adjustable pH response was expected to have potential as drug carriers for controlled release.

Fabrication of polymeric micelles with core–shell–corona structure for applications in controlled drug release

Thermo-responsive polymeric micelles of poly (ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-lactide)-b-poly(N-isopropylacrylamide) (PEG-P(HEMA-PLA)-PNIPAM) with core–shell–corona structure were fabricated for applications in controlled drug release. The graft copolymer of PEG-P(HEMA-PLA)-PNIPAM was self-assembled into core–shell micelles with a densely PLA core and mixed PEG/PNIPAM shells at 25 °C in aqueous media. By increasing the temperature above the lower critical solution temperature of PNIPAM, these core–shell micelles could be converted into core–shell–corona micelles because of the collapse of PNIPAM block on the PLA core as the inner shell and the soluble PEG block stretching outside as the outer corona. Anticancer drug doxorubicin (DOX) was loaded in the polymeric micelles as a model drug. Compared with polymeric micelles formed by liner PEG-b-PLA-b-PNIPAM triblock copolymer, these polymeric micelles exhibited higher loading capacity, and release of DOX from the polymeric micelles with core–shell–corona structure was well-controlled.

Redox-sensitive shell cross-linked PEG–polypeptide hybrid micelles for controlled drug release

Novel PEG–polypeptide hybrid drug carriers, poly(ethylene glycol)-b-poly(L-cysteine)-b-poly(L-phenylalanine) (PEG-PCys-PPhe) triblock copolymers, were prepared via the ring-opening polymerization of amino acid N-carboxyanhydrides. The copolymers can self-assemble to form core–shell–corona micelles in aqueous solutions. The shell of the micelles has the ability to self-cross-link (SCL) by the oxidation of thiol groups in the PCys segments. The morphology and stability of SCL micelles were characterized by TEM, DLS and SEM. The results showed the SCL micelles could hold the physical structure of micelles in severe environments. The in vitro drug release in response to GSH was also studied. It was found that the cross-linked shell could be helpful to reduce the drug loss in the extracellular environment. Under a reductive environment, the micelles would undergo the destruction of the cross-linked shell due to the cleavage of disulfide bonds, followed by accelerated drug release from the micelles. The glutathione-responsive SCL micelles could be easily uptaken by HeLa cells, suggesting these micelles might have great potential in intracellular drug delivery.

Synthesis and Characterization of pH Sensitive Core–Shell–Corona Micelles of Poly(styrene-block-2-vinylpyridine-block-ethylene oxide) ABC Triblock Copolymer in Aqueous Solutions

Abstract The core–shell–corona forming ABC triblock copolymer poly(styrene-block-2-vinylpyridine-block-ethylene oxide), PS–P2VP–PEO, was synthesized using reversible addition fragmentation chain transfer (RAFT) radical polymerization and characterized by NMR and GPC as PS13–P2VP62–PEO47. The aggregation behavior in aqueous solution as a function of pH and temperature was studied. Turbidity measurements were used to monitor the effects associated with change in pH. The pH-sensitive P2VP block (insoluble above pH >5) and resultant protonation/deprotonation phenomenon plays decisive role in the aggregation. We found that spherical micelles of considerably low aggregation number form at pH <5. SANS and DLS characterization indicate the micelles’ size and spherical shape remained virtually constant in the pH range 1 to 5. The size and shape were further confirmed by cryo-TEM.

Incorporation and release behavior of amitriptylene in core–shell–corona type triblock copolymer micelles

A cationic antidepressant drug, amitriptylene (AMT), was successfully incorporated into core–shell–corona micelles of poly[styrene- b-sodium 2-(acrylamido)-2-methyl-1-propanesulfonate- b-ethylene oxide] (PS- b-PAMPS- b-PEO). Zeta-potential measurements revealed that both electrostatic and hydrophobic interactions contributed to the binding of the drug to the polymer. The AMT/PS- b-PAMPS- b-PEO nanocomplexes were characterized by dynamic light scattering, scanning electron microscopy, and transmission electron microscopy. The hydrodynamic diameter of the AMT loaded nanocomplexes decreased from 80 to 40 nm depending on the amount of the drug loaded on the polymer. This is attributed to the cancellation of the negative charge of the PAMPS group by the cationic drug. The AMT/PS- b-PAMPS- b-PEO nanocomplexes were stable in aqueous solution exhibiting no aggregation or no precipitation for several months. Release of the AMT from the nanocomplexes was investigated in vitro in salt-free and 0.1 M NaCl solutions. The drug was released faster in the 0.1 M NaCl solution than in the salt-free solution. This is due to the shielding effect of the salt on the electrostatic interaction. However, in both cases, the drug release mainly occurs by the Fickian diffusion mechanism.

Micelles of poly(styrene- b-2-vinylpyridine- b-ethylene oxide) with blended polystyrene core and their application to the synthesis of hollow silica nanospheres

Core–shell–corona (CSC) micelles of asymmetric triblock copolymer, poly(styrene- b-2-vinylpyridine- b-ethylene oxide) (PS–PVP–PEO), containing polystyrene homopolymer (homo-PS) in the core were successfully prepared in aqueous media. The influence of homo-PS contents over the formation of the micelles was investigated thoroughly by various techniques such as dynamic light scattering (DLS), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and fluorescence spectroscopy. It was found that the size of the PS core of the micelle was increased by the addition of homo-PS as observed by DLS and TEM techniques. The SEM and TEM measurements confirm the spherical morphology of the micelles and enlargement of PS core over the addition of homo-PS. The increase in the PS core volume of the PS–PVP–PEO micelles is attributed to the insertion of homo-PS in the PS core. The micelles have also been demonstrated as facile soft templates for synthesis of hollow silica nanospheres. The average diameter of the spherical hollow particles could be tuned between 30.6 and 38.8 nm with cavity sizes ranging from 20.7 to 28.5 nm using tetramethoxysilane as silica precursors under mild acidic conditions. The facile synthesis of hollow silica using the CSC micelles with different homo-PS contents indicates that the hollow void size can be controlled within a range of several nanometers.

Synthesis and self-assembly of a hydrophilic, thermo-responsive poly(ethylene oxide) monomethyl ether-block-poly(acrylic acid)-block-poly(N-isopropylacrylamide) copolymer to form micelles for drug delivery

A hydrophilic, thermo-responsive triblock copolymer poly(ethylene oxide) monomethyl ether-block-poly(acrylic acid)-block-poly(N-isopropylacrylamide) (MPEO-b-PAA-b-PNIPAM) was synthesized by sequential atom transfer radical polymerization and hydrolysis. These polymers were characterized in detail by 1H NMR, FT-IR and gel permeation chromatography. In aqueous solution, MPEO-b-PAA-b-PNIPAM can self-assemble into core–shell–corona micelles above a LCST of the PNIPAM block. Condensation reactions easily cross-link the PAA shells, which enhances micellar stability. Doxorubicin (DOX), a model drug, was loaded into the core of the polymeric micelles and followed a pattern of thermo-sensitive drug release in vitro in cumulative release studies.

Surface immobilized block copolymer micelles with switchable accessibility of hydrophobic pockets

We report on a novel approach for the design of stimuli-responsive surfaces based on the immobilization of charged ABC triblock terpolymer micelles. The terpolymer consists of a hydrophobic polybutadiene (B) block, a weak anionic poly(methacrylic acid) (MAA) middle block, and a strong cationic end block of quaternized poly(2-(dimethylamino)ethyl methacrylate) (Dq) (BMAADq). In alkaline solutions, this polymer self-assembles into core–shell–corona micelles with a hydrophobic B core, a pH-sensitive MAA/Dq intramicellar interpolyelectrolyte complex (im-IPEC) shell, and a cationic corona of excess Dq. These micelles were directly adsorbed onto charged silica as a monolayer creating laterally structured surfaces. The adsorption kinetics was found to follow the theoretical model of random sequential adsorption (RSA). Exposure of the adsorbed micelles to external stimuli (at pH < pKa,apparent of PMAA) induces im-IPEC dissolution due to protonation of the MAA block resulting in a changed composition of the shell and both the length and charge density of the corona. Two types of conformational response to pH trigger and therefore, two types of dynamics coupled to short and long relaxation times are involved in the system. The response to pH cycling was shown to be reversible on the short-term scale while the long-term exposure to acidic media causes irreversible changes in the morphology of the micelles as a consequence of the micelles' core mobility and slow rearrangement. In particular, we find that exposure to low pH causes a shape transition to a “doughnut”-like morphology, exposing the core parts of the micelles. In contrast, adsorbed micelles with covalently crosslinked B cores show higher stability to irreversible morphology changes while maintaining the reversible response to pH cycling.

Preparation of an amphiphilic triblock copolymer with pH- and thermo-responsiveness and self-assembled micelles applied to drug release

A novel amphiphilic ABC triblock copolymer, poly( N-isopropylacrylamide)-b-poly(styrene-alternate-maleic anhydride)-b-polystyrene (PNIPAAm-b-PSMA-b-PSt), was designed and synthesized by reversible addition fragmentation chain transfer polymerization. The copolymer can disperse in aqueous media at room temperature to self-assemble into pH- and thermo-responsive core–shell–corona micelles, with the hydrophobic PSt block as core, the pH-sensitive PSMA block as shell, and the thermo-sensitive PNIPAAm block as corona. The aqueous copolymer solutions exhibited lower critical solution temperature (LCST) values around 33.5–35 °C under pH 2.1–9.2 conditions via optical transmittance measurements. The critical micelle concentration values of the self-assembled micelles were about 18.6 mg/L at pH 2.1 and 21.1 mg/L at pH 6.9, respectively, relying on fluorescent probe techniques. An interesting pH- and thermo-dependent size of the micelles was observed by dynamic light scattering techniques, which showed that the micelle diameters were about 100–120 nm at 40 °C and 120–160 nm at 25 °C, corresponding to pH 2.1–9.2, respectively. Transmission electron microscopy observations showed that the resulting micelles as uniform nanoparticles existed in regularly spherical shapes. The folic acid-loaded micelles showed a remarkable pH- and thermo-responsive drug release behavior. These results indicate that the copolymer micelles may serve as a promising “intelligent” drug delivery system.

Stimuli responsive associative polyampholytes based on ABCBA pentablock terpolymer architecture

A poly(methyl methacrylate)–poly(acrylic acid)–poly(2-vinyl pyridine)–poly(acrylic acid)–poly(methyl methacrylate) (PMMA–PAA–P2VP–PAA–PMMA), ABCBA pentablock terpolymer was synthesized by “living” anionic polymerization and was studied in aqueous media at different pH conditions in the presence of MeOH. By tuning the pH and/or the solvent selectivity and dielectric constant of the medium, reversible hydrogels of different nature were formed. At low pH the hydrogel is based on a three dimensional network comprising PMMA hydrophobic cores (physical crosslinks) interconnected by complex bridging (elastically active) chains constituted of positively charged P2VP and non-ionic PAA segments. At high pH the hydrogel is transformed reversibly to a negatively charged network the bridging chains of which comprise ionized PAA segments interrupted by hydrophobic P2VP blocks, swellable on MeOH addition. Furthermore, we found conditions for the formation of flower-like micelles of different topologies and nature like core–shell–corona micelles with positively charged corona (pH<2), multicompartment micelles comprising P2VP and PMMA hydrophobic domains (pH 8.3, low MeOH content), micelles constituted of a centrosymmetric compartmentalized core and PAA negatively charged corona (pH 8.3, 30%, 40% MeOH), and core–shell micelles of PMMA cores (pH 8.3, 50% MeOH).