Double Hydrophilic Block Copolymers Research Articles

Designed and tailor-made double hydrophilic block copolymer-graphene nanoplatelet hybrids for reinforcing epoxy thermosets

Because of their propensity to build micellar nanostructures, amphiphilic block copolymers (ABCs) are an appropriate and unique toughening agent for epoxy systems individually on their own and in grafted form. The presence of epoxiphilic and phobic ends in ABCs is responsible for the self-assembly and the micellar structure. Nanofiller-grafted ABCs can effectively enhance the toughness of epoxy via the synergistic interaction of nanofillers and the ABCs. Even though there is sound literature supporting the effect of ABCs in epoxy, the action of double hydrophilic block copolymers (DHBC) in the epoxy matrix is less handled. Hence, the grafting of nanofillers in DHBCs and their subsequent role in tuning the properties of epoxy is a new concept. Hence this paper tries to bridge the gap via studying the effect of grafted fillers based on DHBCs in epoxy matrix. As a result, the current study focuses on the synthesis of double hydrophilic graphene nanoplatelets (rGO-g-DHBC) via nitrogen oxide-mediated polymerization for epoxy toughening application. The prepared rGO-g-DHBC was effectively utilized for epoxy toughening applications, resulting in a 457% improvement in toughness without compromising its inherent tensile strength. The mechanism behind the improved toughness was elucidated with the help of a scanning electron microscope, and the thermal, and rheological characteristics were studied.

Gem-bisphosphonic acid-based double hydrophilic block copolymers: RAFT synthesis and comparative assembly with gadolinium ions for the formation of MRI contrast agents

The synthesis of double hydrophilic block copolymers (DHBCs) with one block containing bisphosphonic acid groups was performed by aqueous RAFT polymerization with two approaches, either starting from a PEO-based macro-chain transfer agent (macro-CTA) or by chain extension of a RAFT-capped bisphosphonic acrylate homopolymer with oligo(ethylene glycol) methyl ether acrylate (OEGA). By complexation with gadolinium and europium ions, these polymers are prone to form hybrid polyionic complexes (HPICs) as evidenced by mono- and multi-angle DLS, TEM and luminescence measurements. The obtained HPICs showed better chemical stability at low pH values compared to previously reported counterparts based on carboxylic and monophosphonic acid groups (i.e., PEO-b-PAA and PEO-b-PVPA respectively). Due to their high relaxivity values, the proposed HPICs show potential as contrast agents for magnetic resonance imaging (MRI).

Ionic strength and anion‐specificity effects on the interfacial behavior of double hydrophilic block copolymer PNIPAM‐b‐POEGA

AbstractIn our prior paper, surface micelles with the core‐shell‐petal structure of the double hydrophilic block copolymer poly(N‐isopropylacrylamide)‐block‐poly[oligo(ethylene glycol) acrylate] (PNIPAM‐b‐POEGA) were successfully evaluated. In this work, ionic strength (under acidic conditions) and anion‐specificity effects (under neutral conditions) on the aggregation behavior of PNIPAM‐b‐POEGA at the air/water interface and the morphologies of its Langmuir–Blodgett (LB) films were systematically studied. Under acidic conditions, the salting‐out effect prevails over the electrostatic shielding effect, and the amide group shells with a slight protonation degree are covered up by the large POEGA petals. Under neutral conditions, the stretching degrees of POEGA blocks at low/moderate salt concentrations are close. At high salt concentrations, the isotherms gradually shift to large molecular areas in the order of the NaCl, Na2SO4, NaNO3, and NaSCN cases. The hysteresis degrees of the monolayers increase with the increase of salt concentrations due to the gradually increased interfacial stretching degree and compression‐induced underwater solubility of POEGA blocks. All the initial LB films of PNIPAM‐b‐POEGA exhibit isolated circular micelles with small cores. Upon compression, the LB films exhibit slightly large micelles because of the possible coalescence of some neighboring cores.

Enhanced stability of gold nanoparticles capped with double hydrophilic block copolymers synthesized by eATRP

AbstractIn this study, the gold nanoparticles (Au NPs) are capped with a novel, well‐defined double hydrophilic block copolymer, poly (ethylene glycols)‐block‐poly(mono‐2‐(methacryloyloxy) ethyl succinate) (PEG‐b‐PSEMA). The PEG‐b‐PSEMA, with long side chains and relatively narrow dispersity index, is successfully prepared by aqueous electrochemically mediated atom transfer radical polymerization using a PEG‐Br macroinitiator (Mn≈2000 g mol−1). By simply mixing PEG‐b‐PSEMA and Au precursor before adding reductants, coulombic interactions occur between the Au precursor and the carboxylate group of the PSEMA, as a result dense Au NPs are formed. This enables the Au NPs to remain dispersed even in the presence of temperature variations, pH adjustments, and incubation in organic solvents. Au NPs were endowed by PEG‐b‐PSEMA with more remarkable catalytic activity in organic solvents of 4‐nitrophenol into 4‐aminophenol than by sodium citrate (Au@citrate) and MeO‐PEG‐OH (Au@PEG). In addition, PEG‐b‐PSEMA‐stabilized Au NPs (Au@PEG‐b‐PSEMA) were also tested for the dye degradation property against Rhodamine‐B in only pH 10 basic solution, and over 99% of dye degradation can be achieved in 9 min. PEG‐b‐PSEMA induces coulombic interactions with Au NPs, providing outstanding stability for catalytic applications in organic or specific acidic‐base environments.

Simple hybrid polymeric nanostructures encapsulating macro-cyclic Gd/Eu based complexes: luminescence properties and application as MRI contrast agent.

Lanthanide-based macrocycles are successfully incorporated into hybrid polyionic complexes, formed by adding a mixture of zirconium ions to a solution of a double-hydrophilic block copolymer. The resulting nanoobjects with an average radius of approximately 10-15 nm present good colloidal and chemical stability in physiological media even in the presence of competing ions such as phosphate or calcium ions. The final optical and magnetic properties of these objects benefit from both their colloidal nature and the specific properties of the complexes. Hence these new nanocarriers exhibit enhanced T1 MRI contrast, when administered intravenously to mice.

Hybrid polyionic complexes as nanoreactors for the synthesis of iron oxide nanoparticles: From size control to modulation of magnetic and catalytic properties

Hybrid polyion complexes (HPICs) obtained from the complexation in aqueous solution of a double hydrophilic block copolymers and metal ions can act as efficient precursors for the controlled synthesis of hybrid nanoparticles. Hence, HPICs based on a mixture of ferrous and ferric ions with poly(ethylene oxide)-block-poly(acrylic acid) were used to initiate, after the addition at 70 °C of a solution of NH4OH, the formation of iron oxide nanoparticles. The careful choice of the molar ratio between polymer and metal ions within HPICs enables to tune the morphology and size of the obtained iron oxide nanoparticles while maintaining the same surface composition. This control of size and composition was further used to highlight the relationship between the size of these particles and their catalytic and magnetic properties.

Hybrid mesoporous silica materials templated with surfactant polyion complex (SPIC) micelles for pH-triggered drug release

New Surfactant PolyIon Complex (SPIC) micelles were assembled by electrostatic complexation of an antibacterial cationic surfactant, cetylpyridinium chloride (CPC), and a double hydrophilic block copolymer (DHBC) containing a neutral comb block of poly(oligo(ethylene glycol)) methyl ether acrylate (PEOGA) and a weak polyacid block of poly(acrylic acid) (PAA). The corresponding SPIC micelles, with a CPC/PAA core and a PEOGA corona, were successfully used as structure directing and functionalizing agents in a soft and sustainable sol-gel strategy, yielding hybrid mesoporous silica (MS) materials with a monomodal pore size distribution centred at 2.8 nm. The influence of synthesis parameters, including the pH, concentrations and ratios of components, was systematically investigated. The obtained hybrid MS materials were intrinsically functional, with PEOGA blocks anchored in silica walls via H-bonding, while weak polyacid blocks, complexed with CPC, were confined within the mesopores. The response of the materials to pH changes (pH 7.4, 4.2 and 3) indicated remarkable stability of the anchored DHBC, while CPC was selectively released under the acidic conditions typical of orodental biofilm microenvironments. This result is noteworthy, since the release of encapsulated amphiphilic drugs into water is less favorable than that of hydrophilic drugs. Owing to the control of their pore and functionality properties, ordered hybrid silica materials templated and functionalized with SPIC systems will be materials of choice for developing pH-responsive biomedical devices using wet processing techniques.

Nanoscale Self-Assemblies from Amphiphilic Block Copolymers as Proficient Templates in Drug Delivery

This review article emphasizes the current enlargements in the formation and properties of the various nanostructured aggregates resulting from the self-assembly of a variety of block copolymers (BCPs) in an aqueous solution. The development of the different polymerization techniques which produce polymers with a desired predetermined molecular weight and low polydispersity is investigated with regard to their technological and biomedical applications; in particular, their applications as vehicles for drug delivery systems are considered. The solution behavior of amphiphilic BCPs and double-hydrophilic block copolymers (DHBCs), with one or both blocks being responsive to any stimulus, is discussed. Polyion complex micelles (PICMs)/polymersomes obtained from the electrostatic interaction of a polyelectrolyte-neutral BCP with oppositely charged species are also detailed. Lastly, polymerization-induced self-assembly (PISA), which forms nanoscale micellar aggregates with controlled size/shape/surface functionality, and the crystallization-driven self-assembly of semicrystalline BCPs facilitated when one block of the BCP is crystallizable, are also revealed. The scalability of the copolymeric micelles in the drug delivery systems and pharmaceutical formations that are currently being used in clinical trials, research, or preclinical testing is emphasized as these micelles could be used in the future to create novel nanomedicines. The updated literature and the future perspectives of BCP self-assembly are considered.

Solvent-Free Synthesis of Multifunctional Block Copolymer and Formation of DNA and Drug Nanocarriers.

The synthesis of well-defined multifunctional polymers is of great importance for the development of complex materials for biomedical applications. In the current work, novel and multi-amino-functional diblock copolymer for potential gene and drug delivery applications was successfully synthesized. A highly efficient one-step and quantitative modification of an alkyne-functional polycarbonate-based precursor was performed, yielding double hydrophilic block copolymer with densely grafted primary amine side groups. The obtained positively charged block copolymer co-associated with DNA, forming stable and biocompatible nanosized polyplexes. Furthermore, polyion complex (PIC) micelles with tunable surface charge and decorated with cell targeting moieties were obtained as a result of direct mixing in aqueous media of the multi-amino-functional block copolymer and a previously synthesized oppositely charged block copolymer bearing disaccharide end-group. The obtained well-defined nanosized PIC-micelles were loaded with the hydrophobic drug curcumin. Both types of nanoaggregates (polyplexes and PIC-micelles) were physico-chemically characterized. Moreover, initial in vitro evaluations were performed to assess the nanocarriers' potential for biomedical applications.

Macromolecular design of pH sensitive, folic acid functionalized double hydrophilic block copolymer nanogels as methotrexate carriers to breast cancer cells

Macromolecular design of pH sensitive, folic acid functionalized double hydrophilic block copolymer nanogels as methotrexate carriers to breast cancer cells

Multiple Carbon Morphologies Derived from Polyion Complex-Based Double Hydrophilic Block Copolymers as Templates and Phenol as a Carbon Precursor.

This study demonstrates the multiple carbon morphology forming abilities of two dissimilar polyion complex (PIC)-based double hydrophilic block copolymers (DHBC) along with three different phenol concentrations when subjecting the blend in aqueous media via a hydrothermal-assisted carbonization strategy. The morphological transition from worm-like to spherical along with granular is found for the blend of oppositely charged poly(ethylene glycol) (PEG)-conjugated poly(amino acid) block copolymers, PEG-poly(l-lysine) (PEG-PLys) and PEG-poly(glutamic acid) (PEG-PGlu), along with three different concentrations of phenol. In contrast, after mixing the combination of PEG-PLys and PEG-poly(aspartic acid) (PEG-PAsp) separately with three different phenol contents, elliptical to irregular to spherical structural transition occurred. Fourier transform infrared and circular dichroism spectroscopic studies indicated that the formation of worm-like hybrid micellar structures is attributed to the presence of the β-sheet structure, whereas spherical-shaped hybrid micellar structures are formed due to the existence of α-helix and random coil structures. We discuss the mechanism for the secondary structure-induced morphology formation based on the theory related to the packing parameter, which is commonly used for analyzing the shape of the micellar structures. Secondary structures of the PIC-based DHBC system are responsible for forming multiple carbon morphologies, whereas these structures are absent in the case of the amphiphilic block copolymer (ABC) system. Furthermore, ABC-based template methods require organic solvent, ultrasonication, and a prolonged solvent evaporation process to obtain multiple carbon morphologies. Scanning electron microscopy observations suggested there is no significant morphological change even after subjecting the hybrid micelles to carbonization at elevated temperatures. Raman scattering studies revealed that the degree of graphitization and the graphitic crystallite domain size of the carbonized sample depend on the phenol content. Carbon materials exhibited the highest specific surface area of 579 m2 g-1 along with a pore volume of 0.398 cc g-1, and this observation suggests that the prepared carbons are porous. Our findings illustrate the facile and effective strategy to fabricate the multiple carbon morphologies that can be used as potential candidates for energy storage applications.

Iron-based hybrid polyionic complexes as chemical reservoirs for the pH-triggered synthesis of Prussian blue nanoparticles

HypothesisHybrid polyion complexes (HPICs) obtained from the complexation in aqueous solution of a double hydrophilic block copolymer and metal ions can act as efficient precursors for the controlled synthesis of nanoparticles. In particular, the possibility to control the availability of metal ions by playing on the pH conditions is of special interest to obtain nanoparticles with controlled size and composition. ExperimentsHPICs based on Fe3+ ions were used to initiate the formation of Prussian blue (PB) nanoparticles in presence of potassium ferrocyanide in reaction media with varying pH values. FindingsComplexed Fe3+ ions within HPICs can be easily released by adjusting the pH value either through the addition of a base/acid or by using a merocyanine photoacid. This allows to modulate the reactivity of Fe3+ ions with potassium ferrocyanide present in solution. As a result, PB nanoparticles with different structures (core, core–shell), composition and controlled size are obtained.

Investigating the electrostatic complexation of BCNO nanoparticles with a stimuli-responsive double hydrophilic graft copolymer

The co-assembly of nanoparticles within double hydrophilic block copolymers (DHBC) via electrostatic complexation is a novel approach for the development of stimuli-responsive nanodrugs with improved bioavailability, biocompatibility, intracellular uptake, and therapeutic efficacy. This study investigated the co-assembly of boron carbon oxynitride (BCNO) nanoparticles within an acid-labile polyethylene glycol-graft-polyethyleneimine (PEG-g-PEI) DHGC as a promising boron nanodrug for boron neutron capture therapy (BNCT). First, BCNO nanoassemblies are prepared by mixing the charged-neutral graft copolymer of PEG-g-PEI into a dispersion of negatively charged BCNO nanoparticles. The BCNO nanoparticles and DHGC complex were characterized using various techniques, including dynamic light scattering, zeta potential, and transmission electron microscopy (TEM). Additionally, this study investigated the change in the hydrodynamic size and zeta potential of the DHGC/BCNO nanoparticle complexation over a wide range of mixing ratios (VBCNO/VDHGC). The results revealed that the BCNO nanoassemblies formed a stable aqueous dispersion at all mixing ratios investigated in this work. In addition, the size and surface charge of the BCNO nanoassemblies can be systematically modulated by adjusting the mixing ratio, molecular weight of the charged segment, ionic strength, and pH of the solution. TEM analysis revealed that the BCNO nanoassemblies formed at a high mixing ratio exhibited polydispersed size and irregular morphologies. With decreasing mixing ratio, the size of the BCNO nanoassemblies decreased, and the cluster exhibited a spherical morphology. In addition, an increase in the molecular weight of the charged PEI segment (10,000, 60,000, and 270,000 g/mole) of the DHGC resulted in the formation of larger BCNO aggregates. Lastly, the stability and pH-responsive behavior of the BCNO nanoassemblies were investigated at pH of 6.9, 6.0, and 5.0. Under mildly acidic conditions, the Schiff base bond cleaved, which resulted in the disassembly of the BCNO aggregates into smaller clusters with a spherical morphology. The DHGC@BCNO nanoassemblies exhibited an exceptional intracellular boron uptake of 627 ng-B/104 cells in MDA-MB-231 triple-negative breast cancer cells. In comparison, cells treated with bare BCNO nanoparticles and [10B]BPA small molecular boron drug demonstrated intracellular boron uptake of only 125 ng-B/104 cells and 17 ng-B/104 cells, respectively. The study highlights the potential of electrostatic colloidal co-assembly as a synthetic tool for developing hybrid nanomaterials with remarkable intracellular boron loading. This represents a significant step towards the development of an efficacious boron drug for boron neutron capture therapy (BNCT).

Self-assembly in newly synthesized dual-responsive double hydrophilic block copolymers (DHBCs) in aqueous solution

Self-assembly in newly synthesized dual-responsive double hydrophilic block copolymers (DHBCs) in aqueous solution

Assemblies of poly(N-vinyl-2-pyrrolidone)-based double hydrophilic block copolymers triggered by lanthanide ions: characterization and evaluation of their properties as MRI contrast agents.

Because of the formation of specific antibodies to poly(ethylene glycol) (PEG) leading to life-threatening side effects, there is an increasing need to develop alternatives to treatments and diagnostic methods based on PEGylated copolymers. Block copolymers comprising a poly(N-vinyl-2-pyrrolidone) (PVP) segment can be used for the design of such vectors without any PEG block. As an example, a poly(acrylic acid)-block-poly(N-vinyl-2-pyrrolidone) (PAA-b-PVP) copolymer with controlled composition and molar mass is synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Mixing this copolymer with lanthanide cations (Gd3+, Eu3+, Y3+) leads to the formation of hybrid polyion complexes with increased stability, preventing the lanthanide cytotoxicity and in vitro cell penetration. These new nanocarriers exhibit enhanced T1 MRI contrast, when intravenously administered into mice. No leaching of gadolinium ions is detected from such hybrid complexes.

Phase Behavior of Double Zwitterionic Block Copolymers in Water: Morphology Transition through Concentration Dependent Selectivity of Water Partitioning

AbstractPhase behavior of double zwitterionic diblock copolymers composed of a poly(carboxybetaine methacrylate) (PCB2) and a poly(sulfobetaine methacrylate) (PSB4) (PCB2n‐b‐PSB4m) has been mapped out in aqueous solutions. Phase diagrams are constructed with polymer concentration, ϕ, ranging from 0.08 to 0.80 and PSB4 volume fraction in the PCB2n‐b‐PSB4ms, fPSB4, ranging from 0.23 to 0.93 at 25 °C. PCB2n‐b‐PSB4m aqueous solutions show symmetric phase diagram above ϕ = 0.55, indicating that water is nearly neutral with respect to PCB2 and PSB4. The morphology transforms from columnar with PCB2 cylinders to lamellar to columnar with PSB4 cylinders with decreasing ϕ, and the phase boundaries exhibit a negative slope below ϕ = 0.45. The morphology transition is rationalized in terms of interfacial curvature modulation through the volume expansion of the PCB2 phase due to the selective water partitioning. The lyotropic mesophase of double hydrophilic block copolymers is a unique molecular compartment for hydrophilic molecules with low interfacial tension.

Development of Double Hydrophilic Block Copolymer/Porphyrin Polyion Complex Micelles towards Photofunctional Nanoparticles

The electrostatic complexation between double hydrophilic block copolymers (DHBCs) and a model porphyrin was explored as a means for the development of polyion complex micelles (PICs) that can be utilized as photosensitive porphyrin-loaded nanoparticles. Specifically, we employed a poly(2-(dimethylamino) ethyl methacrylate)-b-poly[(oligo ethylene glycol) methyl ether methacrylate] (PDMAEMA-b-POEGMA) diblock copolymer, along with its quaternized polyelectrolyte copolymer counterpart (QPDMAEMA-b-POEGMA) and 5,10,15,20-tetraphenyl-21H,23H-porphine-p,p',p″,p'''-tetrasulfonic acid tetrasodium hydrate (TPPS) porphyrin. The (Q)PDMAEMA blocks enable electrostatic binding with TPPS, thus forming the micellar core, while the POEGMA blocks act as the corona of the micelles and impart solubility, biocompatibility, and stealth properties to the formed nanoparticles. Different mixing charge ratios were examined aiming to produce stable nanocarriers. The mass, size, size distribution and effective charge of the resulting nanoparticles, as well as their response to changes in their environment (i.e., pH and temperature) were investigated by dynamic and electrophoretic light scattering (DLS and ELS). Moreover, the photophysical properties of the complexed porphyrin along with further structural insight were obtained through UV-vis (200-800 nm) and fluorescence spectroscopy measurements.

Assembly of Poly(vinylphosphonic acid)-Based Double Hydrophilic Block Copolymers by Gadolinium Ions for the Formation of Highly Stable MRI Contrast Agents.

Mixing double-hydrophilic block copolymers containing a poly(vinylphosphonic acid) block with gadolinium ions in water leads to the spontaneous formation of polymeric nanoparticles. With an average diameter near 20 nm, the nanoparticles are stable after dilution or change of pH and ionic strength. High magnetic relaxivities were measured in vitro, and in vivo magnetic resonance imaging on rats demonstrates the high potential of such polymeric assemblies.

Amphiphilic Block Copolymers: Their Structures, and Self-Assembly to Polymeric Micelles and Polymersomes as Drug Delivery Vehicles.

Self-assembly of amphiphilic block copolymers display a multiplicity of nanoscale periodic patterns proposed as a dominant tool for the 'bottom-up' fabrication of nanomaterials with different levels of ordering. The present review article focuses on the recent updates to the self-association of amphiphilic block copolymers in aqueous media into varied core-shell morphologies. We briefly describe the block copolymers, their types, microdomain formation in bulk and micellization in selective solvents. We also discuss the characteristic features of block copolymers nanoaggregates viz., polymer micelles (PMs) and polymersomes. Amphiphilic block copolymers (with a variety of hydrophobic blocks and hydrophilic blocks; often polyethylene oxide) self-assemble in water to micelles/niosomes similar to conventional nonionic surfactants with high drug loading capacity. Double hydrophilic block copolymers (DHBCs) made of neutral block-neutral block or neutral block-charged block can transform one block to become hydrophobic under the influence of a stimulus (physical/chemical/biological), and thus induced amphiphilicity and display self-assembly are discussed. Different kinds of polymer micelles (viz. shell and core-cross-linked, core-shell-corona, schizophrenic, crew cut, Janus) are presented in detail. Updates on polymerization-induced self-assembly (PISA) and crystallization-driven self-assembly (CDSA) are also provided. Polyion complexes (PICs) and polyion complex micelles (PICMs) are discussed. Applications of these block copolymeric micelles and polymersomes as nanocarriers in drug delivery systems are described.

Synthesis of Double Hydrophilic Block Copolymers Poly(2-isopropyl-2-oxazoline-b-ethylenimine) and their DNA Transfection Efficiency.

Gene delivery is now a part of the therapeutic arsenal for vaccination and treatments of inherited or acquired diseases. Polymers represent an opportunity to develop new synthetic vectors for gene transfer, with a prerequisite of improved delivery and reduced toxicity compared to existing polymers. Here, the synthesis in a two-step's procedure of linear poly(ethylenimine-b-2-isopropyl-2-oxazoline) block copolymers with the linear polyethylenimine (lPEI) block of various molar masses is reported; the molar mass of the poly(2-isopropyl-2-oxazoline) (PiPrOx) block has been set to 7kg mol-1 . Plasmid DNA condensation is successfully achieved, and in vitro transfection efficiency of the copolymers is at least comparable to that obtained with the lPEI of same molar mass. lPEI-b-PiPrOx block copolymers are however less cytotoxic than their linear counterparts. PiPrOx can be a good alternative to PEG which is often used in drug delivery systems. The grafting of histidine moieties on the lPEI block of lPEI-b-PiPrOx does not provide any real improvement of the transfection efficiency. A weak DNA condensation is observed, due to increased steric hindrance along the lPEI backbone. The low cytotoxicity of lPEI-b-PiPrOx makes this family a good candidate for future gene delivery developments.