Ethylene Oxide Triblock Copolymer Research Articles

Interactions between Poloxamers in Aqueous Solutions: Micellization and Gelation Studied by Differential Scanning Calorimetry, Small Angle X-ray Scattering, and Rheology

Poloxamers F88 (EO97PO39EO97) and P85 (EO27PO39EO27) are triblock copolymers of ethylene oxide (EO) and propylene oxide (PO), which have the same hydrophobic PO block. We studied aqueous solutions of these two copolymers by the conjoint use of differential scanning calorimetry (DSC), rheology, and small-angle X-ray scattering (SAXS). The results showed that the temperature-induced micellization of aqueous solutions of F88 and P85 was a progressive process followed by gelation for sufficiently concentrated samples. Gelation was due to the ordered packing of micelles under a hexagonal compact (HC) structure for P85 and a body-centered cubic (BCC) phase for F88. Importantly, the phase diagram of F88/P85 mixtures in water was elucidated and showed the destabilization of the HC phase upon addition of small amounts of F88.

Temperature‐induced cell detachment on immobilized pluronic surface

The Pluronic F68 and F127, a triblock copolymer of ethylene oxide and propylene oxide, was activated using carbonyldiimidazole (CDI), and CDI-activated Pluronic F68 and F127 was subsequently immobilized on the surface of a poly-L-lysine-coated polystyrene tissue culture flask. Cell culture was performed on the Pluronic-immobilized flask. The morphology of fibroblasts (L929 cells) on the Pluronic F127-immobilized flask was mainly spherical, and showed less spreading behavior than that on the Pluronic F68-immobilized flask and conventional tissue culture flask. This observation indicates that L929 cells on Pluronic F127-immobilized flasks were cultured in a bio-inert environment. L929 cells were successively detached from both Pluronic F127-immobilized flask and Pluronic F68-immobilized flask by cooling the flask to 4-15 degrees C. This detachment is due to the hydration and dehydration properties of Pluronic, depending on the temperature. Umbilical cord blood was cultured in the Pluronic F127-immobilized and conventional polystyrene tissue culture flasks at 37 degrees C. The expression ratio of surface markers on hematopoietic stem cells (CD34 and CD133) cultured in the Pluronic F127-immobilized flask was significantly higher than that of the cells in polystyrene tissue culture flask.

Aqueous Gels of Triblock Copolymers of Ethylene Oxide and 1,2‐Butylene Oxide (Type BEB) Studied by Rheometry

AbstractSummary: A triblock copolymer of ethylene oxide and 1,2‐butylene oxide with hydrophilic central block and hydrophobic end blocks, denoted B10E227B10, was prepared and characterised. The frequency dependence of dynamic modulus was determined for micellar solutions in the concentration range of 8–20 wt.‐% and the temperature range of 5–70 °C, and the fluid/gel diagram was established. The results were combined with those reported previously for copolymers B12E227B12 and B12E114B12 to obtain insight into the effect of B‐block and E‐block length on the rheological properties of systems of this type. The results are discussed in terms of micelles forming bridged networks and, at higher concentrations, packing in structured gels.Temperature dependence of the logarithm of storage modulus for aqueous solutions of copolymer B10E227B10 at the concentrations (wt.‐%) indicated. Conditions: f = 1 Hz, A ≈ 0.5%.magnified imageTemperature dependence of the logarithm of storage modulus for aqueous solutions of copolymer B10E227B10 at the concentrations (wt.‐%) indicated. Conditions: f = 1 Hz, A ≈ 0.5%.

Interactions of Hydrophobically Modified Polyvinylamine with Pluronic Triblock Copolymer Micelles

The heats associated with the addition of triblock copolymers of ethylene oxide and propylene oxide (PEO-PPO-PEO pluronics) to solutions of linear polyvinylamine, with N-substituted pendant octyl groups (HMPVAm), were measured as functions of pH and pluronic structure. The interactions were exothermic with the overall enthalpy decreasing with increasing pH from 5 to 10. Surprisingly, the heat effect increased with increasing pluronic hydrophilicity; however, no enthalpy change was observed in the absence of micelles. The results were quantitatively modeled by assuming two competing processes-micellar dissolution and HMPVAm coating of micelles, preventing dissolution.

Bioinert Surface of Pluronic-Immobilized Flask for Preservation of Hematopoietic Stem Cells

The bioinert materials on which cells do not proliferate, differentiate, nor de-differentiate should be useful for the culture and preservation of stem cells. The Pluronic F127, a triblock copolymer of ethylene oxide, and propylene oxide was activated using carbonyldiimidazole (CDI), and CDI-activated Pluronic was subsequently immobilized on the surface of a lysine-coated polystyrene tissue culture flask. The morphology of fibroblasts (L929 cells) on the Pluronic-immobilized flask was spherical, and did not show spreading behavior. This observation indicates that L929 cells on the Pluronic-immobilized flask were cultured in a bioinert environment. The expression ratio of surface markers on hematopoietic stem cells (CD34 and CD133) cultured in the Pluronic-immobilized flask was significantly higher than that in polystyrene tissue culture flask and commercially available bioinert flask (i.e., low cell binding cultureware). This is caused by the existence of hydrophilic segments of Pluronic F127 on the Pluronic-immobilized flask.

Rheological Behavior of Aqueous Micellar Solutions of a Triblock Copolymer of Ethylene Oxide and 1,2-Butylene Oxide: B10E410B10

A triblock copolymer of ethylene oxide and 1,2-butylene oxide, denoted B10E410B10, was prepared by sequential oxyanionic polymerization and characterized by 13C NMR spectroscopy and gel permeation chromatography. Micellization and the formation of micelle clusters in dilute aqueous solution, the latter a consequence of micelle bridging, was confirmed by dynamic light scattering, and average association numbers of the micelles were determined by static light scattering for T = 20-40 degrees C. The frequency dependence of the dynamic storage and loss moduli was investigated for solutions in the range of 5-20 wt %. Comparison with results for poly(oxyethylene) dialkyl ethers (10 wt %, T = 25 degrees C) indicated that the viscoelasticity of a copolymer with terminal B10 hydrophobic blocks was roughly equivalent to one with terminal C14 alkyl chains. The temperature dependence of the modulus was investigated for 15 wt % solutions at T = 5-40 degrees C. Superposition of the data led, via an Arrhenius plot, to an activation energy for the relaxation process of -40 kJ mol(-1). The negative value contrasts with the positive values found for poly(oxyethylene) dialkyl ethers and related HEUR copolymers with urethane-linked terminal alkyl chains. This difference is attributed to the block-length distribution in copolymer B10E410B10, whereby the activation energy of the relaxation process has a positive contribution from the disengagement of B blocks from micelles but a negative contribution from micellization. The negative value of the activation energy for solutions of B10E410B10 was confirmed by determining the temperature dependence of the zero-shear viscosity of its 15 wt % solution.

Preparation and characterization of non-ionic block co-polymer templated mesoporous silica membranes

We report on the preparation and characterization of mesoporous silica membranes via micellar templating using the non-ionic ethylene oxide–propylene oxide–ethylene oxide tri-block copolymer surfactant, Pluronic P123, as a template under various template/silica volume percentages ( V TS%). The silica membranes were prepared by dip coating silica sols onto porous α-alumina supports followed by calcination to remove the template. The membranes were characterized by single gas permeation and permporometry measurements. Using a V TS% of 33 we found that silica membranes comprised of three dip/fire cycles resulted in highly reproducible continuous membranes with minimal defects. Helium and nitrogen permeance values were of the order of 10 −6 mol m −2 s −1 Pa −1. The pore size distribution, determined from permporometry measurements, indicated a dominant peak at 5 nm diameter and approximately 10% microporosity. In addition, there was 8–10% permeance through pores with diameters between 15 and 40 nm. At higher V TS% (47.5 and 65) the silica membranes had considerable bypass flow. The pore size distribution (PSD) of the membrane via permporometry indicated a shift to smaller values for the membrane when compared to the PSD of the powder from the calcined dipping sol, determined by nitrogen adsorption/desorption.

Lipid composition determines interaction of liposome membranes with Pluronic L61

Triblock copolymers of ethylene oxide (EO) and propylene oxide (PO) of EO n/2PO mEO n/2 type (Pluronics) demonstrate a variety of biological effects that are mainly due to their interaction with cell membranes. Previously, we have shown that Pluronics can bind to artificial lipid membranes and enhance accumulation of the anti-tumor drug doxorubicin (DOX) inside the pH-gradient liposomes and transmembrane migration (flip-flop) of NBD-labeled phosphatidylethanolamine in the liposomes composed from one component—lecithin. Here, we describe the effects caused by insertion of other natural lipids in lecithin liposomes and the significance of the lipid composition for interaction of Pluronic L61 with the membrane. We used binary liposomes consisting of lecithin and one of the following lipids: cholesterol, phosphatidylethanolamine, ganglioside GM1, sphingomyelin, cardiolipin or phosphatidic acid. The influence of the additives on (1) membrane microviscosity; (2) binding of Pluronic L61; (3) the copolymer effect on lipid flip-flop and membrane permeability towards DOX was studied. The results showed that insertion of sphingomyelin and cardiolipin did not influence membrane microviscosity and effects of Pluronic on the membrane permeability. Addition of phosphatidic acid led to a decrease in microviscosity of the bilayer and provoked its destabilization by the copolymer. On the contrary, cholesterol increased microviscosity of the membrane and decreased binding of Pluronic and its capacity to enhance flip-flop and DOX accumulation. Analogous tendencies were revealed upon incorporation of egg phosphatidylethanolamine or bovine brain ganglioside GM1. Thus, a reverse dependence between the microviscosity of membranes and their sensitivity to Pluronic effects was demonstrated. The described data may be relevant to mechanisms of Pluronic L61 interaction with normal and tumor cells.

Promoter- and strain-selective enhancement of gene expression in a mouse skeletal muscle by a polymer excipient Pluronic P85

Amphiphilic triblock copolymers of ethylene oxide and propylene oxide (Pluronic) significantly enhanced expression of plasmid DNA in the skeletal muscle. In the presence of Pluronic P85 (P85) high levels of expression of a reporter gene (luciferase) were sustained for at least 40 days and the area under the gene expression curve increased by at least 10 times compared to the DNA alone. The effect of Pluronic depended on the strain of the mouse and the type of the promoter used. Thus, P85 enhanced luciferase expression by 17 to 19-fold in immunocompetent C57Bl/6 and Balb/c mice, while no enhancement was observed with athymic Balb/c nu/nu mice. Furthermore, P85 activated the expression of luciferase gene driven by CMV promoter, NFκB and p53 response elements. There was much less or no effect on the gene driven by SV40 promoter or AP1 and CRE response elements. Overall, the promoter selectivity suggested that Pluronic induced transcriptional activation of gene expression by activating the p53 and NFκB signaling pathways. In addition Pluronic increased the number of DNA copies and thus affected initial stages of gene transfer in a promoter selective manner.

Block Copolymers of Ethylene Oxide and Phenyl Glycidyl Ether: Micellization, Gelation, and Drug Solubilization

Three triblock copolymers of ethylene oxide and phenyl glycidyl ether, type E(m)G(n)E(m), where G = OCH2CH(CH2OC6H5) and E = OCH2CH2, were synthesized and characterized by gel-permeation chromatography, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, and NMR spectroscopy. Their association properties in aqueous solution were investigated by surface tensiometry and light scattering, yielding values of the critical micelle concentration (cmc), the hydrodynamic radius, and the association number. Gel boundaries in concentrated micellar solution were investigated by tube inversion, and for one copolymer, the temperature and frequency dependence of the dynamic moduli served to confirm and extend the phase diagram and to highlight gel properties. Small-angle X-ray scattering was used to investigate gel structure. The overall aim of the work was to define a block copolymer micellar system with better solubilization capacity for poorly soluble aromatic drugs than had been achieved so far by use of block copoly(oxyalkylene)s. Judged by the solubilization of griseofulvin in aqueous solutions of the E(m)G(n)E(m) copolymers, this aim was achieved.

Analysis of Poly(oxyethylene) and Poly(oxypropylene) Triblock Copolymers by MALDI-TOF Mass Spectrometry

Triblock copolymers of ethylene oxide (EO) and propylene oxide (PO) are widely used in the chemical industry as nonionic surfactants. Triblock copolymers can be arranged in a EO-PO-EO or PO-EO-PO sequence. This arrangement results in an amphiphilic copolymer, in which the block sequence and block length determine the properties of the copolymer. MALDI-TOF MS was used to analyze various triblock copolyethers: EO-PO-EO (Mn =2000 g.mol(-1)), PO-EO-PO (Mn = 2000 g.mol(-1)), and a random copolymer EO/PO (Mn = 2500 g.mol(-1)). Data treatment was assisted by using a homemade software allowing a picture of monomer composition of oligomers from the mass spectra. MALDI-TOF mass spectra of EO/PO copolymers were shown to depend strongly on the number of laser shots, relative proportions of polymer/salt, and the nature of the matrix. An unsaturated byproduct was detected. Its presence was demonstrated by prefractionation of copolymers by SEC before MALDI-TOF analysis, and its content was estimated by 1H NMR. The formation of layers inside the MALDI deposit was evidenced by varying the number of laser shots. Lighter oligomers of the copolymer, unsaturated byproduct, or both would be in the core of the deposit, coated with heavier oligomer. The layer formation depends on the nature of the matrix and the quantity of added salt. DHB matrix with a relative high sodium salt content induces layer formation inside the deposit, whereas dithranol matrix or low salt content does not. Consequently, an optimization of experimental parameters in order to estimate the lighter oligomers or unsaturated byproduct content or to obtain the actual representation of the monomer contribution in the copolymers from the MS data only seems obviously critical. MALDI-TOF mass spectrometry is obviously a powerful technique to analyze copolymers, but a careful survey of the experimental parameters is required. The combination of MALDI-TOF MS with separations techniques and NMR brings precious complementary information.

Unusual Micelle and Surface Adsorption Behavior in Mixtures of Surfactants with an Ethylene Oxide−Propylene Oxide Triblock Copolymer

Micellization and adsorption at the air-solution interface of binary mixtures of the triblock copolymer of ethylene oxide and propylene oxide, EO23PO52EO23 (EPE), and the surfactants sodium dodecyl sulfate (SDS), dodecyl trimethylammonium chloride (DTAC), and tetraethylene glycol monooctyl ether (C8EO4) have been studied by neutron reflectivity and surface tension. The synergistic attractive interaction between the polymer and the ionic surfactants has been analyzed in the framework of the pseudo phase approximation and gives rise to a stronger interaction for EPE/SDS than EPE/DTAC. In contrast, the interaction of the nonionic surfactant C8EO4 with the copolymer EPE shows an unexpected and rather different behavior, resulting in a strongly repulsive interaction, characterized by a positive interaction parameter. The neutron reflectivity measurements of the surface excess, where the predicted and measured surface excesses are directly compared, provide evidence that challenges the applicability of the pseudo phase approximation for describing the surface mixing behavior. Structural information on the mixed adsorbed layer provides evidence which in part explains the observed discrepancies between the measured surface excesses and the behavior predicted from the pseudo phase approximation. Furthermore the structural evidence can be use to rationalize the differences in behavior observed between the ionic and nonionic surfactants.

Effect of Ethanol on the Rheological Properties of Water‐Rich Gels of Diblock Copolymer E43B11

AbstractSummary: The effect of added ethanol on the rheological behaviour of aqueous solutions of diblock copolymer E43B11 (E = oxyethylene unit, B = oxybutylene unit) has been investigated. Thermally reversible sol‐gel transitions were observed for concentrated solutions of the copolymer in solutions containing 0–30 wt.‐% ethanol. Storage (G′) and loss (G″) moduli and yield stress (σy) were used to define hard and soft gel phases. The introduction of 10 wt.‐% ethanol did not alter the phase behaviour greatly, whereas higher ethanol concentrations had a large effect, which differed in kind from that reported for triblock copolymers of ethylene oxide and propylene oxide, type EPE.Temperature dependence of the logarithm of (•) storage and (○) loss modulus for 20 wt.‐% copolymer in 10 wt.‐% ethanol.magnified imageTemperature dependence of the logarithm of (•) storage and (○) loss modulus for 20 wt.‐% copolymer in 10 wt.‐% ethanol.

Effect of additives on the cloud points of two tri-block copolymers in aqueous solution

The cloud points (CP) of aqueous solutions of two ethylene oxide–propylene oxide–ethylene oxide tri-block copolymers (EO) 10(PO) 16(EO) 10 and (EO) 1(PO) 17(EO) 1 were measured in the presence of additives, such as salts, alkalis, acids, polymer and ionic surfactant. The results obtained in this study indicated that salts decrease the CP of the two tri-block copolymers in the order of NaCl>CaCl 2>MgCl 2 and Na 3PO 4>Na 2SO 4>NaCl. Alkalis caused a sharp drop of CP of the two tri-block copolymers. Acids increased the CP. Water soluble polymer such as polyvinylpyrrolidone (PVP), hydrolysis polyacrylamide (HPAM) and cation-polyacryamide (cation-PAM) decreased the CP. Ionic surfactants such as sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB) increased the CP. The extent of lowering depends on the structure and concentration of additives and the number of ethylene oxide group of tri-block copolymers.

High molecular arborescent polyoxyethylene with hydroxyl containing shell

Arborescent polyoxyethylene of high molar mass (2×10 5 g/mol) and narrow molar mass distribution was synthesized in a three-stage process. In the first stage a triblock copolymer of ethylene oxide (central block, DP ca. 90) and 2,3-epoxypropanol-1 (short flanking blocks, DP ca. 5) was synthesized. The potassium alcoholate derived from this copolymer was used to initiate the polymerization of ethylene oxide and the subsequent addition of protected glycidol (1-etoxyethyl glycidyl ether). After deprotection the short polyglycidol blocks were used as branching units for the next generation. Repeated step by step process leads to the ‘pom-pom like’ branched polyoxyethylene macromolecules enriched with the reactive hydroxyl groups in the outer shell. The branched structure of the obtained polymers was evidenced by the size exclusion chromatography and NMR spectroscopy.

Synthesis and Aggregation Behavior of Amphiphilic Block Copolymers in Aqueous Solution: Di- and Triblock Copolymers of Poly(ethylene oxide) and Poly(ethyl acrylate)

Di- and triblock copolymers of ethylene oxide (EO) and ethyl acrylate (EA) were synthesized by the atom transfer radical polymerization technique. The chemical compositions of the di- and triblock copolymers as determined by NMR and gel permeation chromatography are represented by [EO114EA10] and [EA10EO445EA10], respectively. The aggregation behaviors of these polymers in aqueous solutions were studied using a combination of static light scattering (SLS), dynamic light scattering, steady fluorescence, time-resolved fluorescence quenching (TRFQ), and surface tension techniques. The hydrodynamic radii (Rh) of PEO-b-PEA and PEA-b-PEO-b-PEA, where PEO is poly(ethylene oxide) and PEA, poly(ethylene acrylate), in an aqueous solution possess values of 15.3 and 25.5 nm, respectively, and they are independent of the polymer concentrations, which suggest that these micelles are formed via the closed association model. The critical micelle concentration (cmc) for the di- and triblock copolymers as determined from t...

Highly ordered orthorhombic mesoporous silica films

Mesoporous silica films are made by the spin-coating technique using an ethylene oxide––propylene oxide––ethylene oxide triblock copolymer (Pluronic PE6800) as template. After optimization of the polymer concentration in the silica sol, films are textured and organized over all the thickness. They exhibit an orthorhombic symmetry ( a=16.0 nm, b=10.2 nm, c=23.0 nm) with the b-axis perpendicular to the substrate. This results from a body-centered cubic (bcc) micellar structure which is deformed along the [0 1 1] bcc cubic axis, i.e. perpendicular to the film plane.

Effects of polyether-modified poly(acrylic acid) microgels on doxorubicin transport in human intestinal epithelial Caco-2 cell layers

Novel microgels composed of cross-linked copolymers of poly(acrylic acid) and Pluronics were evaluated as possible permeation enhancers for doxorubicin transport using Caco-2 cell monolayers as a gastrointestinal model. Pluronic, triblock copolymers of ethylene oxide (EO) and propylene oxide (PO), were chosen to represent the most hydrophobic (Pluronic L61 and L92 with average compositions of EO 3PO 30EO 3 and EO 8PO 52EO 8, respectively) and the relatively hydrophilic (Pluronic F127 with average formula EO 99PO 67EO 99) extremes of this class of block copolymers. The weight ratio of Pluronic to poly(acrylic acid) in the microgels was set at 45:55. By inhibiting the P-glycoprotein (P-gp)-mediated doxorubicin efflux from the cells and enhancing the passive influx, the microgels were shown to enhance the overall cell absorption of doxorubicin. The enhancement effect was more pronounced than with a known penetration enhancer, Pluronic L61, and was comparable to that of Pluronic L92. Microgels exhibited synergism of the doxorubicin transport enhancement with Verapamil, a known inhibitor of the P-gp. The effects of the microgels were studied using the hydrophilic marker ([ 14C]mannitol) test and the MTT assay. Transepithelial electrical resistance (TEER) studies demonstrated that the microgels decreased TEER to about 80% of initial values, but these minor effects were fully reversible, indicating viability of the cells after incubation with microgels. No significant enhancement of [ 14C]mannitol transport by microgels was observed, relative to Carbopol 934NF (control polymer). Cytotoxicity studies confirmed that the transport-enhancing properties of the microgels were not due to damage of the Caco-2 cell monolayers.

Micellization and Gelation of Triblock Copolymers of Ethylene Oxide and Styrene Oxide in Aqueous Solution

Nine triblock copolymers of ethylene oxide and styrene oxide (type EmSnEm, E = oxyethylene, S = oxyphenylethylene, n and m = number-average block lengths) were prepared by sequential oxyanionic polymerization. Surface tensiometry was used to determine critical micelle concentrations (cmc's) and standard enthalpies of micellization, and isothermal titration calorimetry was used to confirm the enthalpy of micellization. Light scattering was used to determine micellar association numbers and hydrodynamic radii. Phase diagrams defining regions of hard and soft gel were determined by tube inversion and Couette rheometry. Comparison is made with reported results for diblock copolymers of ethylene oxide and styrene oxide and, so far as possible, with results for triblock copolymers of ethylene oxide and styrene. Compilation of values of the cmc for three series of triblock copoly(oxyalkylene)s, EmSnEm, EmBnEm (B = oxybutylene), and EmPnEm (P = oxypropylene), reveals a discontinuity in the block length dependence of log(cmc) at S6 and B12.

Aqueous micellar solutions of a triblock copolymer of ethylene oxide and 1,2-butylene oxide, B12E114B12. Scaling the viscoelasticity of fluid and gel

Aqueous solutions of triblock copolymer B12E114B12 have been characterised rheometrically over the concentration range 10–40 wt.% and at several temperatures. Through micellar bridging the micellar interaction is weakly attractive. A wide variety of linear viscoelastic behaviours are observed, and it is shown that they can be superposed onto a master curve of the type developed by Trappe and Weitz (Phys. Rev. Lett., 2000, 85, 449) for conventional colloidal suspensions of weakly-attractive particles.