Hydrophilic Block Copolymers Research Articles

Fabrication and characterization of high flux poly(vinylidene fluoride) electrospun nanofibrous membrane using amphiphilic polyethylene‐block‐poly(ethylene glycol) copolymer

AbstractElectrospun nanofiber membranes (ENM) made of polymers such as polysulfone and poly(vinylidene fluoride) (PVDF) have a much higher contact angle (CA) and also more hydrophobic when compared to the virgin polymers. For water treatment applications, membranes with hydrophilic nature are highly desirable in order to achieve high flux and less fouling potentials. Hence, in the present study, highly hydrophilic electrospun nanofiber membranes (ENMs) were prepared by blending PVDF polymer with amphiphilic polyethylene‐block‐poly (ethylene glycol) (PE‐b‐PEG) copolymer. Resulting amphiphilic ENMs were highly porous (77%–92%) and the breaking elongation of 140% with a young's modulus of 2.55 MPa was observed. When compared with the control PVDF membrane, PE‐b‐PEG blended ENMs revealed higher water permeation flux owing to the enrichment of the hydrophilic PEG segments at the membrane surface, which was confirmed by using X‐ray photoelectric spectroscopy and Energy‐dispersive spectroscopy measurements. When compared to the phase inversion process (CA of 97.3°) blended ENM had CA of 0°, which indicates that besides hydrophilic block copolymer segments, the nature of membrane formation also contributes its role in influencing the hydrophilicity of the membrane. This improved hydrophilicity in combination with larger pore sizes of the PVDF/ PE‐b‐PEG membranes have contributed to enhancement of pure water flux, protein solution permeability and water flux recovery, which can be applied potentially for water treatment applications.

Iron chelation cancer therapy using hydrophilic block copolymers conjugated with deferoxamine.

Cancer cells have high iron requirements due to their rapid growth and proliferation. Iron depletion using iron chelators has a potential in cancer treatment. Previous studies have demonstrated that deferoxamine (DFO) specifically chelates Fe(III) and exhibited antitumor activity in clinical studies. However, its poor pharmacokinetics has limited the therapeutic potential and practical application. Although polymeric iron chelators have been developed to increase the blood retention, none of previous studies has demonstrated their potential in iron chelation cancer therapy. Here, we developed polymeric DFO by the covalent conjugation of DFO to poly(ethylene glycol)‐poly(aspartic acid) (PEG‐PAsp) block copolymers. The polymeric DFO exhibited iron‐chelating ability comparable with free DFO, thereby arresting cell cycle and inducing apoptosis and antiproliferative activity. After intravenous administration, the polymeric DFO showed marked increase in blood retention and tumor accumulation in subcutaneous tumor models. Consequently, polymeric DFO showed significant suppression of the tumor growth compared with free DFO. This study reveals the first success of the design of polymeric DFO for enhancing iron chelation cancer therapy.

Anthracene based photo-tunable polymers with excimer emission

The aggregation properties of a diblock and a triblock copolymer in the aqueous phase has been investigated by photophysical and microscopy methods. Both copolymers possess photoresponsive hydrophobic poly(9-anthrylmethyl methacrylate) (PAN) block and hydrophilic polyethylene oxide (PEO) block whereas the triblock copolymer have an additional polystyrene (PSt) block at the middle. The amphiphilic copolymers, PAN-b-PEO and PAN-b-PSt-b-PEO, were synthesized by atom transfer radical polymerization (ATRP) method. Self-assembly of these individual copolymers in water leads to the formation of uniform spherical supramolecular assemblies. The morphology of the resultant spheres was disturbed by the illumination of the turbid aqueous solutions with 360 nm UV light accomplished by the photosolvolysis of the anthracenylmethyl ester. This irreversible photodissociation virtually transforms the amphiphilic diblock copolymer to a double hydrophilic block copolymer whereas the triblock copolymer because of its central PSt block was transformed into a bolaamphiphile. Complete micellar dissociation obtained in the case of diblock was not observed in the case of vesicular aggregates of the triblock copolymer. We also found that compared to the completely dissolved state, aggregation resulted in the pronounced excimer emission of the anthracene copolymers.

Synthesis of Amphiphilic and Double Hydrophilic Star-like Block Copolymers and the Dual pH-Responsiveness of Unimolecular Micelle

A series of amphiphilic star-like triblock copolymers with well-defined molecular architectures, molecular weight, and narrow polydispersity were successfully synthesized by sequential atom transfe...

Photocatalytically active block copolymer hybrid micelles from double hydrophilic block copolymers

Herein, we demonstrate that double hydrophilic block copolymers can be used for the preparation of photocatalytically active organic/inorganic hybrid micelles. This is realized by immobilization of CdS nanoparticles for photocatalytic water splitting within well-defined poly(2-iso-propyl-2-oxazoline)-block-poly(2-acrylamido glycolic acid) (PiPrOx-b-PAGA) block copolymers. The prepared PiPrOx-b-PAGA/CdS hybrid nanostructures were characterized regarding morphology, structure, and optical properties by UV/Vis and photoluminescence (PL) spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS). Our results confirm spherical inorganic-organic micelles containing ultra-small CdS nanoparticles with photoluminescent character within the core. Afterwards, these hybrid nanostructures were used for photocatalytic H2 production in the presence of triethanol amine (TEOA) as sacrificial reagent in water under visible-light illumination (λ ≥ 470 nm), revealing 18-fold increased activity compared to bare CdS nanoparticles. The enhanced photocatalytic activity can be attributed to several factors, such as 3D confinement within micellar nanostructures, the presence of ultra-small CdS nanoparticles, or an improved stability of CdS nanoparticles within the micellar core. Overall, we demonstrate that double hydrophilic BCP can be an interesting platform for the formation of photocatalytically active micellar nanostructures, leading to materials with potential relevance for photocatalysis.

Ratiometric Fluorescent Mapping of pH and Glutathione Dictates Intracellular Transport Pathways of Micellar Nanoparticles.

Visualization of intracellular transport pathways is crucial to investigate the internalization mechanism and understand the intracellular behavior of nanomaterials. Herein, we rationalized the design of micellar nanoparticles (NPs) for ratiometric fluorescent mapping of intracellular pH and glutathione (GSH), two essential parameters for maintaining normal cellular functions. Specifically, pH-sensitive naphthalimide-based probe (NPI) and pH-inert rhodamine B (RhB) were covalently labeled to double hydrophilic block copolymers (DHBCs) using the thiolactone chemistry, enabling the covalent attachment of NPI and RhB to one molecule with a redox-responsive disulfide linkage. The dually labeled DHBCs exhibited blue/orange dual emissions in acidic pH, which was further converted into green/orange dual emissions in neutral pH because of the deprotonation of NPI moieties and the sole green emission in the presence of GSH at neutral pH because of the decreased Förster resonance energy transfer efficiency between an NPI donor and an RhB acceptor as a result of GSH-mediated cleavage of disulfide bonds. These remarkable ratiometric fluorescence changes allowed for not only the simultaneous mapping of the intracellular pH and GSH but also the intracellular transport pathways of internalized NPs.

Degradable double hydrophilic block copolymers and tripartite polyionic complex micelles thereof for small interfering ribonucleic acids (siRNA) delivery

Polymer vectors for gene therapy have been largely investigated as an alternative to viral vectors. In particular, double hydrophilic block copolymers (DHBCs) have shown potential in this domain, but to date studies mainly focus on non-degradable copolymers, which may be a restriction for further development. To overcome this limitation, we synthesized a DHBC (PEG43-b-PCL12(COOH)6.5) composed of a poly(ethylene glycol) (PEG) non-ionic and bioeliminable block and a degradable carboxylic acid-functionalized poly(ε-caprolactone) (PCL) block. The potential of this DHBC as an original vector for small interfering ribonucleic acids (siRNA) to formulate tripartite polyionic complex (PIC) micelles with poly(lysine) (PLL) was evaluated. We first studied the impact of the charge ratio (R) on the size and the zeta potential of the resulting micelles. With a charge ratio R = 1, one formulation with optimized physico-chemical properties showed the ability to complex 75% of siRNA. We showed a stability of the micelles at pH 7.4 and a disruption at pH 5, which allowed a pH-triggered siRNA release and proved the pH-stimuli responsive character of the tripartite micelles. In addition, the tripartite PIC micelles were shown to be non-cytotoxic below 40 µg/mL. The potential of these siRNA vectors was further evaluated in vitro: it was found that the tripartite PIC micelles allowed siRNA internalization to be 3 times higher than PLL polyplexes in murine mesenchymal stem cells, and were able to transfect human breast cancer cells. Overall, this set of data pre-validates the use of degradable DHBC as non-viral vectors for the encapsulation and the controlled release of siRNA, which may therefore constitute a sound alternative to non-degradable and/or cytotoxic polycationic vectors.

Surface Micelle Structures and Monolayer Compression Moduli of Double Hydrophilic Block Copolymer

At the air/water interface, amphiphilic block copolymers are well-known to form typical surface micelles composed of hydrophobic block cores and hydrophilic block coronas. However, the micelle/aggr...

Aggregation and Crosslinking of Poly(N,N‐dimethylacrylamide)‐b‐pullulan Double Hydrophilic Block Copolymers

Aggregation and Crosslinking of Poly(<i>N,N</i>‐dimethylacrylamide)‐<i>b</i>‐pullulan Double Hydrophilic Block Copolymers

Crystallization vs Metal Chelation: Solution Self-Assembly of Dual Responsive Block Copolymers

We herein report the synthesis and characterization of dual stimuli-responsive poly(2-iso-propyl-2-oxazoline)-block-poly(2-acrylamido glycolic acid) (PiPrOx-b-PAGA) double hydrophilic block copolymers (BCPs) by an effective combination of ring-opening and reversible addition–fragmentation chain transfer (RAFT) polymerization. The resulting materials are responsive toward several external triggers: (1) the PiPrOx segment undergoes a coil-to-globule transition upon heating above the cloud point temperature (TCP), (2) the PAGA block chelates M2+ metal ions and provides straightforward access to nanostructured hybrid materials, and (3) prolonged heating above the TCP for PiPrOx enables crystallization-driven solution self-assembly (CDSA) toward anisotropic micelles and superstructures. We are further able to show that the cloud point temperature (TCP) of PiPrOx-b-PAGA micelles can be tuned from ∼30 to 68 °C by varying either the BCP composition (PiPrOx to PAGA ratio) or by the amount of metal ions being present. The different aggregates were characterized by transmission electron microscopy (TEM), wide-angle X-ray scattering (WAXS), and dynamic light scattering (DLS). Our results indicate that micellar size, shape, and TCP are closely connected to BCP composition and the nature of chelated metal ions. In our opinion, such inorganic–organic hybrid materials are of interest with regard to (photo)catalysis, as sensors, or as potential drug delivery systems.

Aggregation and Crosslinking of Poly(N,N‐dimethylacrylamide)‐b‐pullulan Double Hydrophilic Block Copolymers

AbstractThe self‐assembly of polymers is a major topic in current polymer chemistry. In here, the self‐assembly of a pullulan based double hydrophilic block copolymer, namely pullulan‐b‐poly(N,N‐dimethylacrylamide)‐co‐poly(diacetone acrylamide) (Pull‐b‐(PDMA‐co‐PDAAM)) is described. The hydrophilic block copolymer induces phase separation at high concentration in aqueous solution. Additionally, the block copolymer displays aggregates at lower concentration, which show a size dependence on concentration. In order to stabilize the aggregates, crosslinking via oxime formation is described, which enables preservation of aggregates at high dilution, in dialysis and in organic solvents. With adequate stability by crosslinking, double hydrophilic block copolymer (DHBC) aggregates open pathways for potential biomedical applications in the future.

RAFT polymerization of tertiary sulfonium zwitterionic monomer in aqueous media for synthesis of protein stabilizing double hydrophilic block copolymers

AbstractThe reversible addition‐fragmentation chain‐transfer (RAFT) polymerization of a tertiary sulfonium‐containing zwitterionic monomer (N‐acryloyl‐L‐methionine methyl sulfonium salt: A‐Met[S+]‐OH) was performed in aqueous media in the presence of a water‐soluble chain‐transfer agent (CTA). Several parameters, such as the radical initiator, nature of the salt used as an additive, polymerization temperature, and solvent (water, buffer solution, and mixed solvents), were studied. The polymerization of A‐Met(S+)‐OH in acetate buffer using a trithiocarbonate‐type CTA having two carboxylic acid moieties proceeded in a controlled fashion at 45°C, as confirmed by the low polydispersity of the products (M w/M n &lt; 1.1) and pre‐determined molecular weights. Poly(ethylene glycol)‐based macro‐CTA was also employed for the polymerization of A‐Met(S+)‐OH in mixed solvents (H2O/EtOH and H2O/DMF = 70/30 vol%) to afford novel nonionic‐zwitterionic double hydrophilic block copolymers. The chain extension of the hydrophilic poly(N,N‐dimethylacrylamide) macro‐CTA with A‐Met(S+)‐OH was well controlled in pure water under the appropriate conditions, resulting in the formation of block copolymers with “as‐designed” chain structures and relatively low dispersities (M w/M n &lt; 1.3). The resulting sulfonium‐containing double hydrophilic block copolymers having optimal nonionic/zwitterionic balance were efficient protein‐stabilizing agents.

Comprehensive study of the formation of stable colloids of Cu[sbnd]Al layered double hydroxide assisted by double hydrophilic block copolymers

The formation of stable aqueous colloidal suspensions of CuAl layered double hydroxide (LDH) assisted by double-hydrophilic block copolymers was investigated. It was of utmost importance since the direct preparation LDH colloids of controlled size is still a major challenge; moreover, regarding the CuAl system, the mechanism of formation of the LDH phase is not well understood yet. CuAl LDH nanoparticles were obtained by complexing Cu2+ and Al3+ cation mixture (Cu2+/Al3+ = 2) with an asymmetric poly(acrylamide)-b-poly(acrylic acid) block copolymer, followed by metal cation hydroxylation. The mechanism of formation of the CuAl LDH was studied and compared to that of MgAl LDH. ICP-MS analysis of the hybrid polyion complex (HPIC) micelles obtained at increasing complexation ratio, i. e. the ratio of the molar concentration of complexing acrylate group of DHBC to M2+ and Al3+ cations (R = AA/(M2+ + Al3+)), showed higher selectivity of DHBC toward Al3+ and, among M2+ cations, for Cu2+ than for Mg2+. Hydroxylation of the HPIC micelles led to macroscopic precipitates at R values below flocculation thresholds, i. e. R1 = 0.43 for DHBC/Cu-Al and 0.13 for DHBC/Mg-Al suspensions, while stable suspensions were formed above R1. The hydrodynamic diameter (Dh) of the colloids determined by DLS decreased from 160 to 50 nm and from 350 to 50 nm in the DHBC/Cu-Al and DHBC/Mg-Al colloids, respectively, when R increased from R1 to 1. XRD and TEM analyses of the dried colloidal suspensions (R > R1) revealed the presence of CuAl LDH and MgAl LDH phases and elemental analyses confirmed that M(II)/Al = 2. Particle sizes were lower in CuAl LDH than in MgAl LDH. Titration curves corresponding to progressive hydroxylation of DHBC/Cu(or Mg)-Al solutions at fixed complexation ratio R allowed establishing that formation of CuAl and MgAl LDH obeyed to a similar sequential mechanism in two steps but involving different aluminum hydroxide precursors according to the different pH values of precipitation. CuAl LDH was obtained by combination of aluminum poly(hydr)oxide species with dissolved copper-based species at pH ~ 5.5, while MgAl LDH resulted from combination of Al(OH)3 and dissolved Mg2+ at pH ~ 8.

Synthesis of Double Hydrophilic Block Copolymers Poly(2-oxazoline-b-ethylenimine) in a Two-Step Procedure

The synthesis of double hydrophilic block copolymers (DHBCs) containing a polyethylenimine (PEI) and a poly(2-alkyl-2-oxazoline) in two steps was investigated in this study. First, well-defined cop...

Synthesis of a Triple-Responsive Double Hydrophilic Block Copolymer Prodrug Using a Reducible RAFT–ATRP Double-Head Agent

Reduction and acidic pH- dual sensitive micelles have been frequently highlighted to present a synergistic effect on promotion of intracellular drug release for enhanced therapeutic efficiency comp...

Effects of Halide Anions on the Solution Behavior of Double Hydrophilic Carboxy-Sulfobetaine Block Copolymers.

The solution behavior of the double polybetaine block copolymer poly(2-((2-(methacryloyloxy)ethyl)dimethylammonio)acetate)-block-poly(3-((2-(methacryloyloxy)ethyl)dimethylammonio)propane-1-sulfonate (PGLBT-b-PSPE) in sodium halide aqueous solutions was investigated. In the presence of salt ions, the unimer-to-micelle transition of PGLBT-b-PSPE that originated by Coulombic attraction between PSPE motifs was suppressed and shifted to much lower temperatures. The transition was hindered more by increases in the salt concentration because of additional counterion binding on the ionized site of PGLBT-b-PSPE chains, which screens the dipole-dipole attractions. The specific ion effect was investigated on four different halides, Cl-, Br-, I-, and F-. Cl- and two chaotropes (Br- and I-) apparently prevented micelle formation, and the hindering effectiveness on the PSPE pairing followed the general Hofmeister series of anions: I- > Br- > Cl-. More chaotropic anions strongly maintained the polymer chains in a fully hydrated state when the same amount of salts was incorporated. However, F-, which is classified as a kosmotrope, only made a small contribution to lowering the transition point and led to abrupt transition without showing a gradual phase change prior to the transition. The variations of hydrodynamic radius and zeta potentials of unimers and micelles gave hints of the solvation state of salt-incorporated PGLBT-b-PSPEs in each state. These results suggest that chaotropic halides tend to exist in the vicinity of the diblock polybetaine chain surface and thus prominently influenced the thermoresponsive solution behavior, whereas kosmotropic F- prefers water molecules and causes minor changes in the PGLBT-b-PSPE aqueous solution.

Dual-functional chemical sensor for sensitive detection and bioimaging of Zn2+ and Pb2+ based on a water-soluble polymer

Free lead and zinc ions are toxic to living cells and environment, we develop a multi-responsive fluorescence probe based on water-soluble double hydrophilic block copolymer. The polymer sensor with Schiff moiety can sensitively, selectively and simultaneously fluorescence probe Zn2+ (green) and Pb2+ (blue) through the different fluorescence color. The linear concentration ranges for Pd2+ and Zn2+ were 0.8–10.0 μM and 0–10.0 μM with the detection limits of 0.7 μM and 0.2 μM, respectively. The probe responding to Na+, Mn2+, Fe2+, Fe3+, Cu2+, Zn2+, Cd2+, Al3+, Cr3+, Co2+, Ni2+, Ag+, Ca2+, K+, Mg2+, Ba2+, Hg2+, and Pb2+ displays almost no significant interference with the assay process. The sensing mechanism of the PSAM probe to Pb2+ and Zn2+ was investigated by Job's plot experiment, 1H NMR analysis and density functional theory (DFT), the results show that the nitrogen atom of CHN and oxygen atom of OH may recognize with ions and the Job's plots for the PSAM complexes demonstrate 1:1 complexation, respectively. To achieve its application, the chemosensor is successfully applied to monitor Pd2+and Zn2+ in tap and lake water samples, its ability to monitor free Pd2+ and Zn2+ ions in living cells or in vivo is also validated by the intracellular imaging.

Dual Reduction/Acid-Responsive Disassembly and Thermoresponsive Tunability of Degradable Double Hydrophilic Block Copolymer.

We report a thermoresponsive double hydrophilic block copolymer degradable in response to dual reduction and acidic pH at dual locations. The copolymer consists of a poly(ethylene oxide) block covalently connected through an acid-labile acetal linkage with a thermoresponsive polymethacrylate block containing pendant oligo(ethylene oxide) and disulfide groups. The copolymer undergoes temperature-driven self-assembly in water to form nanoassemblies with acetal linkages at the core/corona interface and disulfide pendants in the core, exhibiting dual reduction/acid responses at dual locations. The physically assembled nanoaggregates are converted to disulfide-core-crosslinked nanogels through disulfide–thiol exchange reaction, retaining enhanced colloidal stability, yet degraded to water-soluble unimers upon reduction/acid-responsive degradation. Further, the copolymer exhibits improved tunability of thermoresponsive property upon the cleavage of junction acetal and pendant disulfide linkages individually and in combined manner. This work suggests that dual location dual reduction/acid-responsive degradation is a versatile strategy toward effective drug delivery exhibiting disulfide-core-crosslinking capability and disassembly as well as improved thermoresponsive tunability.

Synthesis and behaviour of PEG-b-PDEAm block copolymers in aqueous solution

Well-defined double hydrophilic block copolymers (DHBCs) of poly(ethylene glycol)-block-poly(N,N-diethylacrylamide) (PEG-b-PDEAm) were synthesized via a reversible addition-fragmentation chain-transfer (RAFT) polymerization of N,N-diethylacrylamide (DEAm) using dithioester terminated PEG of different chain lengths as macro-chain transfer agents. Controlled molecular weight and narrow molecular weight distribution were achieved as proven by size exclusion chromatography (SEC). Cloud points (CP) were determined via turbidity measurements with ultraviolet-visible spectroscopy (UV–vis) and LCST by differential scanning micro-calorimetry (micro-DSC). They range from 32 to 40 °C depending on the PDEAm length block and its concentration. Above the LCST, fluorescence spectroscopy and dynamic light scattering (DLS) demonstrated that the PEG-b-PDEAm copolymers self-organized into large aggregates. More interestingly, copolymers pre-aggregated at relatively high concentrations below the LCST.

Effects of pH on the Stimuli-Responsive Characteristics of Double Betaine Hydrophilic Block Copolymer PGLBT-b-PSPE.

We investigated the pH-responsive behavior of the carboxybetaine-sulfobetaine diblock copolymer poly(2-(2-(methacryloyloxy)ethyl)dimethylammonio)acetate-block-3-((2-(methacryloyloxy)ethyl)dimethylammonio)propane-1-sulfonate (PGLBT-b-PSPE) in aqueous solution under varying temperatures. Alongside the temperature-responsive PSPE block which induces self-assembly of polymer micelles under the upper critical solution temperature, the PGLBT motifs having protonation sites caused additional changes in the phase behaviors. In acidic conditions where the pH is lower than the pKa of PGLBT-b-PSPE, the transmittance of polymer solutions more abruptly dropped and became cloudy at higher temperatures compared to the case of salt-free solutions. There were two simultaneous diffusive modes in the turbid solutions equivalent to unimers or micelles and large aggregates over a few hundred nanometers. Unlike in neutral and basic conditions, those large aggregates did not disappear after the emergence of the polymer micelles. The trend of the temperature-responsive behavior hardly changed in the alkaline solutions; however, the critical temperature significantly decreased. The surface charge of the unimers and self-assembled objects determined by zeta potential measurement varied from neutral or negative to positive with proton addition and further positively increased below the micelle formation temperature. This indicates the cationization of PGLBT moieties and their arrangement in the outer layer of the polymer micelle surface. In spite of the positively charged outer surface, two fast and slow diffusive modes representing micelles and large clusters were repeatedly observed in acidic solutions, and to some extent, size-grown particles eventually precipitated.