PEO Block Copolymer Research Articles

Dendron-like poly(ε-benzyloxycarbonyl-L -lysine)/linear PEO block copolymers: Synthesis, physical characterization, self-assembly, and drug-release behavior

Dendron-like poly(e-benzyloxycarbonyl-L-lysine)/linear poly(ethylene oxide) block copolymers (i.e., Dm-PZLys-b-PEO, m = 0 and 3; Dm are the propargyl focal point poly(amido amine) dendrons having 2m primary amine groups) were for the first time synthesized by combining ring-opening polymerization (ROP) of e-benzyloxycarbonyl-L-lysine N-carboxyanhydride (Z-Lys-NCA) and click chemistry, where Dm-PZLys homopolypeptides were click conjugated with azide-terminated PEO. Their molecular structures and physical properties were characterized in detail by FTIR, 1H NMR, gel permeation chromatography, differential scanning calorimetry, polarized optical microscopy, and wide angle X-ray diffraction. Both homopolypeptides and copolymers presented a liquid crystalline phase transition for PZLys block, and the transition was irreversible. Moreover, the degree of crystallinity of PEO block within linear copolymers decreased from 96.2% to 20.4% with increasing PZLys composition, whereas that within dendritic copolymers decreased to zero. The secondary conformation of PZLys progressively changed from β-sheet to α-helix with increasing the chain length. These copolymers self-assembled into spherical nanoparticles in aqueous solution, and the anticancer drug doxorubicin-loaded nanoparticles gave a similar morphology compared with their blank counterparts. The drug-loaded nanoparticles showed a triphasic drug-release profile at aqueous pH 7.4 or 5.5 and 37 °C and sustained a longer drug-release period for about 2 months. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012

Interactions of PEO–PPO–PEO block copolymers with lipid membranes: a computational and experimental study linking membrane lysis with polymer structure

Poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block co-polymers (PEO–PPO–PEO, sold as Pluronics, Poloxamers, Tetronics) are a widely used class of amphiphilic materials for different biological applications. In fact for certain members of the Pluronics series, the interactions of block segments with living cells alter the lipid membrane properties and facilitate the permeation of drugs. A fuller understanding of the molecular mechanisms underpinning these interactions is essential for ensuring their safety and efficacy in biomedical applications and to inform the design of new amphiphilic copolymers for potential use in a clinical setting. In this paper, by means of atomistic molecular dynamics simulations and membrane lysis assays, we investigate the relationship between the molecular conformations of a subset of the Pluronic copolymers (L31, L61, L62 and L64) and their haemolytic activity. Our computational studies suggest that the hydrophilic blocks in these copolymers interact with the polar head groups of lipid molecules, resulting in a predicted modification of the structure of the membranes. Parallel membrane lysis assays in human erythrocytes indicate differences in the rates of haemolysis, as a result of incubation with these polymers, that correlate well with the predicted interactions from the atomistic simulations. The computational data thus provide a putative mechanism to rationalize the available experimental data on membrane lysis by these copolymers and quantitatively agree with haemoglobin release endpoints measured when copolymers with the same molecular weight and structure as of those modelled are incubated with erythrocytes. The data further suggest some new structure–function relationships at the nanoscale that are likely to be of importance in determining the biological activity of these otherwise inert copolymers.

Structures of PEP–PEO Block Copolymer Micelles: Effects of Changing Solvent and PEO Length and Comparison to a Thermodynamic Model

Structures of poly(ethylene propylene)–poly(ethylene oxide) (PEP–PEO) block copolymer micelles were determined from small-angle X-ray scattering and static light scattering and compared to predictions from a thermodynamic model. Both the corona block length and the solvent water–ethanol ratio were changed, leading to a thorough test of this model. With increasing ethanol fraction, the PEP core–solvent interfacial tension decreases, and the solvent quality for PEO changes. The weight-average block masses were 5.0 kDa for PEP and 2.8–49 kDa for PEO. For the lowest PEO molar mass and samples in pure water (except for the highest PEO molar mass), the micelles were cylindrical; for other conditions they were spherical. The structural parameters can be reasonably well described by the thermodynamic model by Zhulina et al. [Macromolecules2005, 38 (12), 5330–5351]; however, they have a stronger dependence on solvent composition and PEO molar mass than predicted.

A Study of Structure Parameters of Block Copolymers Polystyrene-Polyethylene Oxides

Block copolymer consists of two and more than two of different polymer links. Epoxy terminated polydtyrene (Ps-ep) active polymer was used to polymerize polystyrene (Pst)-polyethylene oxide (Peo) block copolymer P (st-b-eo). There were the mixtures of (Ps-ep), (Pst), (Peo) and P (st-b-eo) in the polymerization. It is necessary to separate (Ps-ep), (Pst), (Peo) and P (st-b-eo) in the mixtures in order to determine structure parameters of P (st-b-eo) block copolymers. We can know for certain their types of ABA, BAB and AB of polystyrene (A)-Polyethylene oxides (B) block copolymers with analysis of gel permeation chromatography (GPC).

Effect of Hydrophobicity of PEO–PPO–PEO Block Copolymers on Micellization and Solubilization of a Model Drug Nimesulide

AbstractThe present work explored the molecular implications governing the solubilization of a model drug nimesulide (NIM) in micelles of ethylene oxide‐propylene oxide (EO–PO) triblock copolymers. The aggregation behavior and solubilization studies on four copolymers each with the same mol mass of central PPO block equal to 2,250 and varying % PEO was examined by means of UV–VIS. Moreover, high‐sensitivity differential scanning calorimetry, and Fourier transform infrared spectrometry measurements were used to evaluate the critical micellization temperature. The solubilization at different temperatures (30, 37, 45 °C), pH (2 to 10) and in the presence of added sodium chloride (0–2 M) was monitored and the partition coefficient (P) and the free energy of solubilization (ΔGso) were calculated. The site of solubilization of NIM in micelles was also probed. The NIM solubility decreased with increases in the PEO molecular weight; the drug resides in the micelle core.

Structure of PEP–PEO block copolymer micelles: exploiting the complementarity of small-angle X-ray scattering and static light scattering

The structure of large block copolymer micelles is traditionally determined by small-angle neutron scattering (SANS), covering a large range of scattering vectors and employing contrast variation to determine the overall micelle morphology as well as the internal structure on shorter length scales. The present work shows that the same information can be obtained by combining static light scattering (SLS) and small-angle X-ray scattering (SAXS), which provide information on, respectively, large and short length scales. Micelles of a series of block copolymers of poly(ethylene propylene)-b-poly(ethylene oxide) (PEP–PEO) in a 70% ethanol solution are investigated. The polymers have identical PEP blocks of 5.0 kDa and varying PEO blocks of 2.8–49 kDa. The SLS contrasts of PEP and PEO are similar, providing a homogeneous contrast, making SLS ideal for determining the overall micelle morphology. The SAXS contrasts of the two components are very different, allowing for resolution of the internal micelle structure. A core–shell model with a PEP core and PEO corona is fitted simultaneously to the SAXS and SLS data using the different contrasts of the two blocks for each technique. With increasing PEO molecular weight, a transition from cylindrical to spherical micelles is observed. This transition cannot be identified from the SAXS data alone, but only from the SLS data.

Micelles from PEO–PPO–PEO block copolymers as nanocontainers for solubilization of a poorly water soluble drug hydrochlorothiazide

The effect of molecular characteristics of EO–PO triblock copolymers viz. Pluronic® P103 (EO17PO60PEO17), P123 (EO19PO69EO19), and F127 (EO100PO65EO100) on micellar behavior and solubilization of a diuretic drug, hydrochlorothiazide (HCT) was investigated. The critical micellization temperatures (CMTs) and size for empty as well as drug loaded micelles are reported. The CMTs and micelle size depended on the hydrophobicity and molecular weight of the copolymer; a decrease in CMT and increase in size was observed on solubilization. The solubilization of the drug hydrochlorothiazide (HCT) in the block copolymer nanoaggregates at different temperatures (28, 37, 45°C), pH (3.7, 5.0, 6.7) and in the presence of added salt (NaCl) was monitored by using UV–vis spectroscopy and solubility data were used to calculate the solubilization characteristics; micelle–water partition coefficient (P) and thermodynamic parameters of solubilization viz. Gibbs free energy (ΔGs°), enthalpy (ΔHs°) and entropy (ΔSs°). The solubility of the drug in copolymer increases with the trend: P103>P123>F127. The solubilized drug decreased the cloud point (CP) of copolymers. Results show that the drug solubility increases in the presence of salt but significantly enhances with the increase in the temperature and at a lower pH in which drug remains in the non-ionized form.

Nanofibers by Green Electrospinning of Aqueous Suspensions of Biodegradable Block Copolyesters for Applications in Medicine, Pharmacy and Agriculture

Poly(hexamethylene adipate)-PEO block copolymers (PHA-b-PEO) with different PEO contents were synthesized and processed to aqueous suspensions with high solid contents by a solvent displacement method followed by dialysis. The best suspension displayed a solid content of 16 wt.-% and an average particle size of 108 nm. This suspension was mixed with a small amount of high molecular weight PEO and Brij78 and electrospun into corresponding nanofibers. After extraction with water, nanofibers of PHA-b-PEO were obtained. Electrospinning of aqueous suspensions of biodegradable polyesters alleviates concerns regarding safety, toxicology and environmental problems, which are associated with spinning of such polyesters from harmful organic solvents and thereby offers novel perspectives for applications in medicine, pharmacy and agriculture. Electrospinning of polymers from aqueous suspensions avoiding harmful organic solvents is suggested to be "green electrospinning".

Thermally Stable Photocuring Chemistry for Selective Morphological Trapping in Block Copolymer Melt Systems

In this work, we report the novel application of thermally stable photocuring chemistry toward high fidelity translation of block copolymer based melt-state morphologies into their equivalent solid analogues. The thermal stability of the cationic photcuring chemistry allows for both extended thermal processing prior to cure, as well as precise trapping of selected morphologies afforded by the temperature independent initiation mechanism. We demonstrate this powerful approach using a model polyisoprene-b-poly(ethylene oxide) (PI−PEO, fPEO = 0.39, Mn = 10 120 g mol−1) block copolymer, prepared by two step anionic polymerization and subsequent partial epoxidation (7.3−16.8 mol % relative to diene repeat units) with 3-chloroperoxybenzoic acid. Small angle X-ray scattering (SAXS) and dynamic rheology were used to determine morphological behavior of the block copolymers synthesized. The targeted PI−PEO parent block copolymer exhibited multiple melt-state morphologies including crystalline lamellae (Lc), hexagonally packed cylinders (C), bicontinuous gyroid (G), and a final isotropic disordered state (Dis). The partial epoxidation and the addition of the UV activated cationic photoinitiator (4-iodophenyl)diphenylsulfonium triflate (1.0−1.25 mol %) acted only to shift transition temperatures between phases, without disturbing the overall morphological sequence present in the neat, unmodified PI−PEO block copolymer. Exposure of the photacid/block copolymer blends to UV radiation at selected temperatures permitted successful permanent trapping of both the cylinder and gyroid morphologies from a single block copolymer sample, as verified by pre- and postcure SAXS measurements. Importantly, this approach should be applicable to any block copolymer in which cationically polymerizable functional groups can be incorporated.

Evaluation of Isoprene Chain Extension from PEO Macromolecular Chain Transfer Agents for the Preparation of Dual, Invertible Block Copolymer Nanoassemblies

Two RAFT-capable PEO macro-CTAs, 2 and 5 kDa, were prepared and used for the polymerization of isoprene which yielded well-defined block copolymers of varied lengths and compositions. GPC analysis of the PEO macro-CTAs and block copolymers showed remaining unreacted PEO macro-CTA. Mathematical deconvolution of the GPC chromatograms allowed for the estimation of the blocking efficiency, about 50% for the 5 kDa PEO macro-CTA and 64% for the 2 kDa CTA. Self assembly of the block copolymers in both water and decane was investigated and the resulting regular and inverse assemblies, respectively, were analyzed with DLS, AFM, and TEM to ascertain their dimensions and properties. Assembly of PEO-b-PIp block copolymers in aqueous solution resulted in well-defined micelles of varying sizes while the assembly in hydrophobic, organic solvent resulted in the formation of different morphologies including large aggregates and well-defined cylindrical and spherical structures.

PS‐b‐PEO block copolymer thin films as structured reservoirs for nanoscale precipitation reactions

AbstractThin films of PS‐b‐PEO block copolymers were utilized as structured reservoirs for localized nanoscale precipitation reactions. By consecutively immersing the film into solutions of thioacetamide and cadmium chloride, we were able to obtain a monolayer of cadmium sulfide nanostructures on top of the block copolymer film. AFM and grazing incidence small angle X‐ray scattering revealed spherical nanostructures (d = 15 nm) corresponding to the dimensions given by the block copolymer film. © 2010 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 48: 1569–1573, 2010

Micellar solutions of PEO–PPO–PEO block copolymers for in situ phenol removal from fermentation broth

The applicability of aqueous solutions of Pluronics for the removal of the model product phenol was evaluated. Phenol is a chemical that can be produced by a recombinant strain of the solvent tolerant bacterium Pseudomonas putida S12. However, the growth of the micro-organisms and the phenol production is inhibited at low phenol concentrations. The solubility of phenol in aqueous solutions containing micelles of Pluronics F108, F68, P105, L64, P104, P85, P103 and L122 was determined. Additionally, the regeneration behavior of the Pluronics was studied by determining the solubility of phenol in Pluronic unimers after lowering the temperature of the solution to below critical micelle temperature. The phase behavior of Pluronics in the presence of fermentation broth and the growth of P. putida S12 in the presence of Pluronics were studied. Finally, the results obtained in this study were used to estimate the amount of cooling energy needed to obtain 1 g of phenol using Pluronics P85 and P103.

Effect of an amphiphilic diol (Surfynol ®) on the micellar characteristics of PEO–PPO–PEO block copolymers in aqueous solutions

The aggregation and clouding behaviors of a series of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) triblock copolymers, PEO–PPO–PEO (Pluronic ®) containing ethylene oxide (EO) content 30% (P103 and P123), 40% (P84), 50% (P85) and 70% (F87 and F127) in the presence of an amphiphilic diol (C 14diol or Surfynol ®104) were investigated using cloud point, viscometry, dynamic light scattering (DLS) and small angle neutron scattering (SANS). DLS and SANS data reveal micellar growth/transition in the presence of diol; such changes strongly dependant on the EO content and hence on the hydrophilic lipophilic balance (HLB) value of the copolymer. Copolymer with low HLB value showed noticeable growth in the micellar size as compared to one with high HLB. P123 and P103, the least hydrophilic (HLB ∼ 8/9) among the copolymers studied here, show a series of structural changes with the addition of Surfynol. Highly temperature sensitive microstructures and hence the rheological behavior were also observed in P103. These structural changes in micelles are explained in terms of the hydrophobic interaction between the copolymer and diol. The observed results correlate well with the reported HLB values of the block copolymer.

Mechanism of PEO–PPO–PEO micellization in aqueous solutions studied by two-dimensional correlation FTIR spectroscopy

The micellization mechanism of PEO–PPO–PEO block copolymer in aqueous solutions was studied by two-dimensional correlation FTIR spectroscopy. The 1400–1000 cm −1 region was investigated, involving the stretching vibrations of ether band, C–H wagging vibrations of EO methylene groups and C–H symmetric deformation vibrations of PO methyl groups. In the 2D correlated spectra, the hydrous and anhydrous state of the ether band, PO methyl groups, and the two conformations of EO methylene groups were observed. Molecules with different PO lengths and increasing molecular weight were investigated to determine the sequence of association of the separate groups. During temperature-induced micellization, the following changes were detected: firstly, EO methylene groups changed from a gauche state to a trans state; secondly, conformational transitions led to the dehydration of hydrated methyl groups; next, the hydrogen bonding between C–O band and water diminished; and finally, dehydrated groups approached to form hydrophobic cores, resulting in micelle formation. From this variation in the sequence of group associations, it is concluded that aggregates of unimers first formed, then hydrophobic cores formed through the hydrophobic interaction from dehydrated PPO blocks, and proper micelles eventually evolved. The temperature-induced conformational changes are suggested the reason for micellization.

Synthesis and Organization of Three‐Arm‐Star PIB–PEO Block Copolymers at the Air/Water Interface: Langmuir‐ and Langmuir–Blodgett Film Investigations

AbstractThe synthesis of three‐arm‐star (PIB–PEO) block copolymers (BCPs) via azide/alkyne “click” reaction and their behavior at the air/water interface are reported. Starting from a three‐arm‐star allyl‐telechelic PIB (1) prepared by living cationic polymerization, the three‐arm‐star PIB–(CH2N3)3 (2c) was generated via borane addition/oxidation PIB–(CH2OH)3, (2a) followed by reaction with CBr4/PPh3 furnishing PIB–(CH2Br)3 (2b) and then the PIB–(CH2N3)3 (2c) after reaction with trimethylsilyl‐azide/tetrabutylammonium fluoride. The final three‐arm‐star (PIB–PEO) BCPs (4a, 4b) were then generated by azide/alkyne “click” reaction of the PIB–(CH2N3)3 (2c) with alkyne‐telechelic PEOs (3a, 3b) in a biphasic water/toluene mixture, using copper(II) sulfate pentahydrate/sodium ascorbate as the Cu(I)‐regenerative system and microwave irradiation. NMR spectroscopy and MALDI investigations proved the final structure of the three‐arm‐star PIB–PEO BCPs. Subsequent Langmuir‐ and Langmuir–Blodgett films investigations of 4a and 4b reveal the absence of a pancake‐to‐brush transition. Compared to PIB54–(PEO3–OCH3)3 4a, the collapse of PIB54–(PEO16–OCH3)3 4b occurs at higher surface pressures and lower mean molecular area values indicative of stronger anchoring of the PIB block to the air/water interface. Addition of iron‐oxide nanoparticle (Rh = 83 Å) leads to a stabilization of the hydrophobic layer of 4a, thus shifting the collapse to higher surface pressures.magnified image

RAFT polymerization of luminescent boron quinolate monomers

Fluorescent homopolymers and amphiphilic block copolymers were prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of two new styryl-type organoboron monomers; the fluorescence characteristics of PEO block copolymers in aqueous solution were studied.

Protein-loaded PLGA–PEO blend nanoparticles: encapsulation, release and degradation characteristics

The aim of this work was to study the variables that affect the encapsulation and release of proteins from nanoparticles based on poly(lactic-co-glycolic acid; PLGA)–poloxamer and PLGA–poloxamine blend matrices, using bovine serum albumin (BSA) and immuno-γ-globulin (IgG) as model proteins. The nanoparticles were prepared by a solvent diffusion technique, and the studied variables were (1) PLGA molecular weight, (2) type of PEO-block copolymers, (3) protein loading, (4) pH and, (5) volume of the protein solution. Our results showed that the proteins can be efficiently incorporated into and released from the blend matrices. The type of the PEO derivative and the pH of the internal aqueous phase were the most important factors influencing protein encapsulation and release kinetics. Moreover, comparative degradation study of PLGA, PLGA–poloxamer and PLGA–poloxamine nanoparticles confirmed that the degradation and release characteristics of polyester particles can be improved by the incorporation of polyoxyethylene derivatives with different hydrophilia–lipophilia balance.

Solubilization of poorly water-soluble drug carbamezapine in Pluronic ® micelles: Effect of molecular characteristics, temperature and added salt on the solubilizing capacity

The solubilization of a poorly water-soluble antiepileptic drug, carbamazepine (CBZ), in a series of micelle-forming PEO–PPO–PEO block copolymers with combinations of blocks having different molecular weight was studied. The drug solubility and micelle–water partition coefficient ( P) were determined using UV–vis spectroscopy. Dynamic light scattering on copolymer solutions was used to measure size and polydispersity of nanoaggregates. Solubilization of carbamezapine increased with the rise in temperature and concentration of block copolymers, but no significant increase was observed with added salt (NaCl). The solubilization is also discussed from a thermodynamics viewpoint, by considering the standard free energy of solubilization (Δ G°).

Strain rate effect on toughening of nano-sized PEP–PEO block copolymer modified epoxy

A bisphenol A-based epoxy was modified with an amphiphilic poly(ethylene- alt-propylene)– b-poly(ethylene oxide) (PEP–PEO) block copolymer as a toughening agent. PEP–PEO molecules self-assemble into spherical micelles in epoxy with an average diameter of 15 nm and give rise to 180% improvement in fracture resistance. The fracture and tensile behaviors of the PEP–PEO-modified epoxy were investigated at loading rates ranging from 0.51 to 508 mm min −1. The toughened epoxy exhibits mechanical properties that are significantly more rate dependent than the neat epoxy material. As expected, a higher test rate leads to a more brittle behavior of the material and a lower fracture toughness value. With careful systematic study of their micromechanical deformation processes, the observed strain rate dependence is explained. The implications of the current findings on nano-sized rubber toughening of epoxy are also discussed in detail.

Dynamic response of block copolymer wormlike micelles to shear flow

The linear and nonlinear dynamic response to an oscillatory shear flow of giant wormlikemicelles consisting of Pb–Peo block copolymers is studied by means of Fourier transformrheology. Experiments are performed in the vicinity of the isotropic–nematic phasetransition concentration, where the location of isotropic–nematic phase transition lines isdetermined independently. Strong shear-thinning behaviour is observed due to criticalslowing down of orientational diffusion as a result of the vicinity of the isotropic–nematicspinodal. This severe shear-thinning behaviour is shown to result in gradient shear banding.Time-resolved small-angle neutron scattering experiments are used to obtain an insightinto the microscopic phenomena that underlie the observed rheological response.An equation of motion for the order parameter tensor and an expression of thestress tensor in terms of the order parameter tensor are used to interpret theexperimental data, both in the linear and nonlinear regimes. Scaling of the dynamicbehaviour of the orientational order parameter and the stress is found when criticalslowing down due to the vicinity of the isotropic–nematic spinodal is accountedfor.