Synthesis and permeation behavior of membranes from segmented multiblock copolymers containing poly(ethylene oxide) and poly(β-benzyl L-aspartate) blocks

Novel segmented multiblock copolymers ( 7 ) were synthesized by linking poly(ethylene oxide) (PEO) blocks with poly(β-benzyl L -aspartate)(PBLA) blocks via urethane and urea bonds, which were formed by the reaction of 4,4′-methylenediphenyl isocyanate ( 5 ) with the terminal hydroxyl groups of α-hydro-ω-hydroxypoly(oxyethylene) ( 4 ) and the terminal amino groups of poly(β-benzyl L -aspartate)-block-iminohexamethyleneimino-block-poly(β-benzyl L -aspartate) ( 3 ) [prepared from 1,6-hexanediamine ( 1 ) and β-benzyl L -aspartate N-carboxy anhydride ( 2 )], respectively. Membranes with various water contents were obtained from these copolymers by changing the lengths of the PEO and PBLA segments. The study of the permeation of 1-phenyl-1,2-ethanediol, vitamin B₁₂ and myoglobin through the membranes showed a high dependency of the permeability on the molecular weight of the solutes.     

Structure of polystyrene-block-poly(ethylene oxide) diblock copolymer micelles in water

Micellization in water of two homologous series of AB-type diblock copolymers, composed of polystyrene (PS) as the A block and poly(ethylene oxide) (PEO) as the B block, were investigated by small-angle X-ray scattering (SAXS) and dynamic light scattering (DLS). The copolymers have molecular weights M _n in the range 2 000—34 800, and have in a given series, the same number of repeating units of the PS block, (N_PS = 10 and 38), and a variable number of repeating units of the PEO block (N_PEO values in the range 23–704). In order to avoid secondary association of micelles, a dialysis technique was used to prepare the micellar systems, in the case of copolymers having high M _n values of the PS block. The experimental micelle properties such as the core radius R_c and the aggregation number N of non-equilibrium structures, so called “frozen micelles”, obtained by dialysis, were found to be independent of the copolymer characteristics. However, for equilibrium structures, obtained by direct solubilization of the copolymers (N_PS = 10) in water, R_c and N were found to decrease with increasing N_PEO for the homologous series.     

Synthesis and characterization of multiblock copolymers poly[poly(L-lactide)-block-polydimethylsiloxane]

The preparation of multiblock copolymers poly[poly(L -lactide)-block-polydimethylsiloxane] by polycondensation of bifunctional oligomers via hydrosilylation is described. The procedure consists first to synthesize the two bifunctional oligomers α,ω-disilyl-polydimethylsiloxane and α,ω-diallyl-poly(L -lactide). The former is prepared in one step by cationic polymerization of octamethylcyclotetrasiloxane in the presence of 1,1,3,3-tetramethyldisiloxane as end-blocker. Two steps are necessary to prepare α,ω-diallyl-poly(L -lactide). The first one is the polymerization of L-lactide initiated by the system ethylene glycol/tin 2-ethylhexanoate. In a second step, the hydroxyl end-groups of the resulting α,ω-dihydroxy-poly(L -lactide) are transformed, by reaction with allyl isocyanate, into terminal allylic functions. Different multiblock copolymers were prepared by hydrosilylation (catalyzed by hexachloroplatinic acid) using the same α,ω-diallyl-poly(L -lactide) (M?_n = 2000 g · mol ^?1) and various α,ω-disilyl-polydimethylsiloxanes (M?_n from 1 750 to 9 000 g · mol ^?1). The influence of parameters such as temperature, stoichiometry of reactive end-groups and catalyst concentration on the molecular weight of the copolymers was studied. High molecular weight copolymers were obtained (DP_n > 12 by SEC). In addition to the biodegradability of the lactic acid units, the immiscibility of the polydimethylsiloxane and poly(L -lactide) blocks imparts thermoplastic elastomer properties to these copolymers. The crystallinity of the poly(L -lactide) phase is dependent on the molecular weight of the polydimethylsiloxane blocks.     

Surface properties of epoxy systems, 1. Influence of the chemical structure on surface energy of monomers,comonomers and additives

The plate method was used to measure the surface tension of different epoxy prepolymers and different hardeners. The values are correlated to the chemical structure. The effect of molecular weight is very weak for diglycidyl ether of bisphenol A (DGEBA) prepolymers. For α,ω-diamino-terminated poly(propylene oxide) (PPO) oligomers, the surface tension remains constant when M?_n changes. However, the surface tension increases for PPO oligomers when the number of amino end-groups increases, and for α,ω-epoxy-terminated oligomers when M?_n increases. These results are discussed in terms of a competition between the surface tension of the chain ends and the surface tension of the constitutional repeating units. The surface tension of carboxy-(CTBN) and epoxy (ETBN)-terminated butadiene-acrylonitrile random copolymers is lower than the value of DGEBA prepolymers. In homogeneous blends these oligomers have a surfactant effect.     

The Aggregation Behavior of Poly(ethylene oxide)‐Poly(methyl methacrylate) Diblock Copolymers in Organic Solvents

Poly(ethylene oxide)‐poly(methyl methacrylate) and poly(ethylene oxide)‐poly(deuteromethyl methacrylate) block copolymers have been prepared by group transfer polymerization of methyl methacrylate (MMA) and deuteromethyl methacrylate (MMA‐d₈), respectively, using macroinitiators containing poly(ethylene oxide) (PEO). Static and dynamic light scattering and surface tension measurements were used to study the aggregation behavior of PEO‐PMMA diblock copolymers in the solvents tetrahydrofuran (THF), acetone, chloroform, N,N‐dimethylformamide (DMF), 1,4‐dioxane and 2,2,2‐trifluoroethanol. The polymer chains are monomolecularly dissolved in 1,4‐dioxane, but in the other solvents, they form large aggregates. Solutions of partially deuterated and undeuterated PEO‐PMMA block copolymers in THF have been studied by small‐angle neutron scattering (SANS). Generally, large structures were found, which cannot be considered as micelles, but rather fluctuating structures. However, ¹H NMR measurements have shown that the block copolymers form polymolecular micelles in THF solution, but only when large amounts of water are present. The micelles consist of a PMMA core and a PEO shell.     

Cyclic Hydrazide‐Functionalized Poly(ethylene oxide) Frameworks for the Synthesis of pH‐Cleavable Drug‐Carriers and Their Applications for the Stabilization of Gold Nanoparticles

In this paper, two different types of poly(ethylene oxide) (PEO) frameworks with different functional groups such as the thiol group and cyclic hydrazide in the α,ω‐positions bearing “smartness” are introduced. These heterobifunctional PEOs are synthesized via different functionalization approaches using t‐butoxy PEO. Heterobifunctional PEOs, both α‐luminol‐ω‐thiol PEO and α‐thiol‐ω‐cyclic hydrazide PEO, are prepared by chain‐end functionalization of the reactive t‐butoxy PEOs. The chain‐end luminol as a cyclic hydrazide is found to be effective to yield pH‐responsive prodrugs from the reaction with doxorubicin (Dox) yielding corresponding Dox‐tethered PEO. The active t‐butoxy PEO‐initiated block copolymerization of N‐phenylmaleimide (N‐PMI) in acetone yields a block copolymer controlled in the 3‐ to 5‐units range of the N‐PMI group. The deprotection of the t‐butoxy group, followed by tosylation, thioacetylaton, and the Gabriel process, provides corresponding α‐thiol‐ω‐cyclic hydrazide PEO. The functionality yields are almost quantitative (over 98 mol%). Polymeric prodrugs such as Dox‐tethered PEO and folate‐conjugated PEO are successfully employed for the stabilization of gold (Au) nanoparticles. The resulting products are characterized by a combination of proton nuclear magnetic resonance (¹H NMR) spectroscopic, ultraviolet (UV)–visible spectroscopic, Fourier transform infrared (FT‐IR), transmission electron microscopic (TEM), and size‐exclusion chromatographic (SEC) analysis.     

Aminolysis of low-molecular-weight and polymeric 4-nitrophenyl esters

4-Nitrophenyl methacrylate (1a), 4-nitrophenyl esters of some N-methacryloyl-ω-amino acids (1b ?d) and 4-nitrophenyl esters of N-acetyl- and N-methacryloyltryptophane (2a and 2b) were prepared and characterized. Copolymers of 1 a ?d and 2 b with N-2-hydroxypropylmethacrylamide (HPMA), N-isopropylmethacrylamide (iPMA) and N-ethylmethacrylamide (EMA) were also prepared. The 4-nitrophenyl ester content of the copolymers was determined spectrophotometrically from their UV absorption and from the UV absorption of the 4-nitrophenolate ion which is released upon hydrolysis of the active esters with 0,1 M sodium hydroxide. The difference between these values depends on both the type of polymerizable active ester used and the comonomer. The proportion of non-hydrolyzable structure is especially high in the case of copolymers containing 4-nitrophenyl esters of the methacryloylated α-amino acids 1b and 2b . The formation of non-hydrolyzable structures is likely due to side reactions which occur during polymerization. The polymers prepared by copolymerization of the polymerizable 4-nitrophenyl esters were not found to be suitable for the preparation of polymeric fluorescent probes by a chemical modification route. It was found that the rate of aminolysis of low-molecular-weight and polymeric activated esters increases with increasing the number of methylene groups in the N-(ω-aminoalkyl)-5-dimethylamino-1- naphthalenesulfonamides (dansylamines) 3a–f .     

New macromolecular micelles based on degradable amphiphilic block copolymers of malic acid and malic acid ester

To study the behaviour of polymeric materials under in‐vivo conditions, degradable macromolecular micelles based on amphiphilic block copolymers of poly(β‐malic acid) as hydrophilic units and poly(β‐malic acid alkyl esters) as hydrophobic blocks are studied. First three β‐substituted β‐lactones, benzyl malolactonate, butyl malolactonate, and butyl 3‐methylmalolactonate were prepared, starting from aspartic acid. A prepolymer based on benzyl malate units was synthesized by anionic ring‐opening polymerization of benzyl malolactonate. Then the carboxylic end groups of this prepolymer were used as initiator for the polymerization of the second lactone, e. g. butyl malolactonate or butyl 3‐methylmalolactonate. The prepolymer and block copolymers have been characterized by ¹H NMR and size exclusion chromatography (SEC). Degradable macromolecular micelles were prepared from the block copolymers by two different methods and characterized by dynamic light scattering and fluorescence measurements using pyrene as a fluorescence probe. It was shown that these amphiphilic degradable copolymers form stable micelles under physiological conditions (10^–2 M phosphate buffered solution, PBS, pH 7.4 with 0.15 M NaCl). Moreover, it was displayed that the characteristics of these macromolecular micelles, especially the critical micellar concentration (cmc), are depending on the chain length of both blocks and on the chemical structure of the hydrophobic block. A very important conclusion of this study is, that micelle formation is dependent on the pH of the medium. Therefore, besides the fact that such micelles are potentially degradable into non‐toxic low molecular weight molecules, their properties and stability were proven to be pH‐dependent. This property can lead development of an “intelligent” drug carrier able to release the entrapped biologically active molecule depending on the pH values.     

Spherical Compound Micelles with Lamellar Stripes Self‐Assembled from Star Liquid Crystalline Diblock Copolymers in Solution

Detailed investigations on the self‐assembly of amphiphilic star block copolymers composed of three‐arm poly(ethylene oxide) (PEO) and poly(methacrylate) (PMAAz) with an azobenzene side chain (denoted as 3PEO‐b‐PMAAz) into stable spherical aggregates with clear lamellar stripes in solution are demonstrated. Four block copolymers, 3PEO₁₂‐b‐PMA(Az)₃₃, 3PEO₂₂‐b‐PMA(Az)₃₁, 3PEO₂₂‐b‐PMA(Az)₆₂, and linear PEO₆₈‐b‐PMA(Az)₃₁, are synthesized. The liquid crystalline properties of the block copolymers are studied by differential scanning calorimetry, polarized optical microscopy techniques, and wide‐angle X‐ray diffraction. The morphologies of the compound micelles self‐assembled in tetrahydrofuran (THF)/water mixtures are observed by means of transmission electron microscopy and scanning electron microscopy. The size of the spherical micelles is influenced by the self‐assembly conditions and the lengths of two blocks. The well‐defined three‐arm architecture of the hydrophilic blocks is a key structural element to the formation of stable spherical compound micelles. The micelle surface integrity is affected by the lengths of PEO blocks. The lamellar stripes are clearly observed on these micelles. This work provides a promising strategy to prepare functional stable spherical compound micelles self‐assembled by amphiphilic block copolymers in solution.     

Telechelic poly(ε-caprolactone) terminated at both ends with OH groups and its derivatization

The synthesis of highly uniform (1,08 ≤ M _w/M _n ≤ 1,13) telechelic poly(ε-caprolactone) terminated at both ends with OH groups and its derivatization leading to poly(ε-caprolactone) with pyrene end-groups are described. The synthesis, carried out in THF at room temperature, involves initiation with (CH₃CH₂)₂AlO(CH₂CH₂O)₃Al(CH₂CH₃)₂, leading to poly(ε-caprolactone) macromolecules growing at both ends. The active centers were deactivated with acetic acid, giving macromolecules with OH end-groups. Reaction of α,ω-dihydroxypoly(ε-caprolactone), HO-poly(εCL)-OH, with 4-(1-pyrenyl)butyryl chloride yields α,ω-di-1-pyrenylpoly(ε-caprolactone), Py-poly(εCL)-Py. Polymers are characterized by GPC, ¹H NMR, and UV spectroscopies. The UV spectra of polymers with pyrene end-groups are compared with the UV spectra of the model compound.     

Polymers by “criss-cross”-cycloaddition, 7. Segmented block copolymers

“Criss-cross”-cycloaddition of 4,4′-diisocyanatodiphenyl ether and 4-methoxybenzaldazine was used to synthesize α,ω-diisocyanato telechelics of molecular weights between 1 600 and 3 900. These precursors were reacted with different α,ω-dihydroxy functionalized aliphatic polyethers to produce segmented block copolymers in which the precursors obtained by cycloaddition reaction provide hard segment domains embedded in a polyether soft segment matrix. The resulting materials were soluble in common organic solvents such as tetrahydrofuran and chloroform and were characterized by spectroscopic techniques (¹H-, ¹³C NMR, IR spectroscopy) as well as gel permeation chromatography (GPC) for molar mass determination. The block copolymers were molded in a hot stage press, and the resulting samples were characterized by differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and stress-strain measurement. The materials with a hard segment fraction below 0.36 and a molecular weight above M?_n = 90 000 were elastomers with ultimate elongations above 700%.     

Synthesis and properties of star shaped block copolymers of styrene and ethylene oxide

Star shaped block copolymers with two arms of polystyrene (PS) blocks and two arms of poly(oxyethylene) (PEO) blocks were synthesized by coupling living PS anions first and then living PEO anions, using SiCl₄ as the coupling agent, while the star shaped block copolymers with two arms of PS blocks and one arm of PEO block were prepared by using CH₃SiCl₃ as the coupling agent. The products were purified by extractions, and the purified copolymers were characterized by GPC, IR, ¹H NMR and torsional braid analysis. The crystalline, emulsifying and complexing properties and also the phase transfer catalytic effect of the star shaped block copolymers were studied.     

Free radical synthesis of α,ω-primary amino functionalized polyisoprene through the functional thermal inferter [bis(N-(2-phthalimidoethyl)piperazine)]thiuram disulfide

The primary amino functional iniferter [bis(N(2-phthalimidoethyl)piperazine)]thiuram disulfide (PEPTD) was synthesied and characterized. Thermal polymerization of isoprene in the presence of the initiator afforded α,ω-functionalized polyisoprene with primary amino end-groups after cleavage of the phthalimido group with butylamine. The kinetics of polymerization of isoprene using this iniferter was studied at 80, 85, 90 and 100°C. Interestingly, isoprene showed a complex kinetic behavior. The different parameters, related to initiation, chain transfer and primary radical termination reactions, as well as the constants for thermal decomposition of the initiator, were determined. From the Arrhenius plot, the activation energy of the overall decomposition constant of PEPTD (2 f k_d) was calculated to be 110 kJ/mol. The functionality of the telechelics was examined by GPC.     

Association and surface properties of diblock copolymers of ethylene oxide and DL-lactide in aqueous solution

Diblock copolymers of ethylene oxide and DL -lactide (E_mL_n copolymers) were prepared by sequential anionic polymerisation and characterised by gel permeation chromatography (GPC) and ¹³C NMR. Their association and surface properties in aqueous solution were studied by surface tension and dynamic and static light scattering. Comparison of the critical micelle concentrations (cmc) and micelle association numbers (N_w) of the E_mL_n copolymers with published values for oxyethylene/oxybutylene (E_mB_n) copolymers indicated a slightly lower hydrophobicity for a lactide unit: i.e. L ? 0.75B. The temperature dependence of the cmc of copolymer E₄₂L₁₂ was analysed to obtain a standard enthalpy of micellisation Δ_micH⁰ ≈ 40 kJ · mol^?1.     

Association Behavior between End‐Functionalized Block Copolymers PEO‐PPO‐PEO and Poly(acrylic acid)

Summary: The end groups of ABA‐triblock copolymers HO–PEO–PPO–PEO–OH, (PEO – poly(ethylene oxide), PPO – poly(propylene oxide)), have been modified with ammonia, ethylene diamine and linear polyethylenimine (LPEI) by substitution of the α,ω‐ditosyl ester of the triblock copolymer (TsO–PEO–PPO–PEO–OTs) with amines, or by the hydrolysis of the corresponding poly(2‐methyl‐2‐oxazoline) (PMeOx) containing ABCBA block copolymers. The latter block copolymer structures have been obtained by the polymerization of MeOx using TsO–PEO–PPO–PEO–OTs as a macro‐initiator. Adding poly(acrylic acid) (PAA) to these (poly)amine terminated block copolymers leads to the formation of networks through a combination of PAA–PEO hydrogen bonding and PAA–(poly)amine acid‐base reaction. Depending on the number of amino groups at both chain ends of the block copolymer, the corresponding complexes behave as liquids, gels or precipitates. Introduction of as little as 1–5 wt.‐% block copolymers H₂N–PEO–PPO–PEO–NH₂ or H₂NCH₂CH₂NH–PEO–PPO–PEO–NHCH₂CH₂NH₂ to the system of HO–PEO–PPO–PEO–OH/PAA leads to viscous liquids with strong shear‐thickening behavior.

Reversible gel formation via the ternary PAA/HO–PEO–PPO–PEO–OH/H₂N–PEO–PPO–PEO–NH₂ system under shear conditions.     

Synthesis and Aggregation Behaviors of Well‐Defined Thermoresponsive Pentablock Terpolymers With Tunable LCST

A series of thermoresponsive pentablock terpolymers, poly(N‐isopropylacrylamide)‐b‐poly(ethylene oxide)‐b‐poly(propylene oxide)‐b‐poly(ethylene oxide)‐b‐poly(N‐isopropylacrylamide), is prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization. The effect of NIPAM and PPO block lengths on lower critical solution temperature (LCST), critical micelle concentration (cmc), and aggregation number (N_agg) is investigated via UV–Vis spectroscopy and steady‐state fluorescence spectroscopy. The results show that upon increasing the block lengths, LCST and cmc decrease, while N_agg increases. TEM observation shows that associated spherical‐like particles are evidenced below the LCST of the terpolymers, and regular or irregular spherical micelles or even intermicellar aggregates are observed above the LCST.     

Synthesis and Characterization of Amphiphilic Poly(ethylene oxide)‐block‐poly(hexyl methacrylate) Copolymers

We describe the preparation of amphiphilic diblock copolymers made of poly(ethylene oxide) (PEO) and poly(hexyl methacrylate) (PHMA) synthesized by anionic polymerization of ethylene oxide and subsequent atom transfer radical polymerization (ATRP) of hexyl methacrylate (HMA). The first block, PEO, is prepared by anionic polymerization of ethylene oxide in tetrahydrofuran. End capping is achieved by treatment of living PEO chain ends with 2‐bromoisobutyryl bromide to yield a macroinitiator for ATRP. The second block is added by polymerization of HMA, using the PEO macroinitiator in the presence of dibromobis(triphenylphosphine) nickel(II), NiBr₂(PPh₃)₂, as the catalyst. Kinetics studies reveal absence of termination consistent with controlled polymerization of HMA. GPC data show low polydispersities of the corresponding diblock copolymers. The microdomain structure of selected PEO‐block‐PHMA block copolymers is investigated by small angle X‐ray scattering experiments, revealing behavior expected from known diblock copolymer phase diagrams.

SAXS diffractograms of PEO‐block‐PHMA diblock copolymers with 16, 44, 68 wt.‐% PEO showing spherical (A), cylindrical (B), and lamellae (C) morphologies, respectively.     

Janus Micelle Formation Induced by Protonation/Deprotonation of Poly(2‐vinylpyridine)‐block‐Poly(ethylene oxide) Diblock Copolymers

A novel approach to amphiphilic polymeric Janus micelles based on the protonation/deprotonation process of poly(2‐vinylpyridine)‐block‐poly(ethylene oxide) (P2VP‐b‐PEO) diblock copolymers in THF is presented. It is found that addition of HCl to the micelles solution of P2VP‐b‐PEO copolymers leads to the formation of vesicles. Subsequently mixing a small amount of hydrazine monohydrate with the vesicle solution can induce the dissociation and reorganization of the vesicles into Janus micelles. When HCl is replaced by HAuCl₄ precursors, composite Janus particles containing gold in P2VP blocks are obtained.

     

Synthesis and structural study of an ABA block copolymer consisting of poly(γ-benzyl L-glutamate) as the a block and poly(ethylene oxide) as the B block

ABA-type block copolymers composed of poly(γ-benzyl L -glutamate) (PBLG) as the A component and poly(ethylene oxide) (PEO) as the B component were synthesized by polymerization of γ-benzyl L -glutamate N-carboxyanhydride initiated by primary amines located at both ends of the PEO chain. The morphology examined by transmission electron microscopy using ruthenium tetroxide staining revealed a lamellar type of microphase separation of the copolymers. From circular dichroism measurements in ethylene dichloride solution, as well as from infrared spectra measurements in the solid state, it was found that the polypeptide block exists in the α-helical conformation, as in PBLG homopolymer. Wide-angle X-ray diffraction patterns for the block copolymers depend on the casting solvent and show basically similar reflections as the PBLG homopolymer.     

Thermosensitive AB4 four-armed star PNIPAM-b-HTPB multiblock copolymer micelles for camptothecin drug release

Thermo-sensitive poly(N-isoproplacrylamide)_m-block-hydroxyl-terminated polybutadiene-block-poly(N-isoproplacrylamide)_m (PNIPAM_m-b-HTPB-b-PNIPAM_m, m = 1 or 2) block copolymers, AB₄ four-armed star multiblock and linear triblock copolymers, were synthesized by ATRP with HTPB as central blocks, and characterization was performed by ¹H NMR, Fourier transform infrared, and size exclusion chromatography. The multiblock copolymers could spontaneously assemble into more regular spherical core–shell nanoscale micelles than the linear triblock copolymer. The physicochemical properties were detected by a surface tension, nanoparticle analyzer, transmission electron microscope (TEM), dynamic light scattering, and UV–vis measurements. The multiblock copolymer micelles had lower critical micelle concentration than the linear counterpart, TEM size from 100 to 120 nm, and the hydrodynamic diameters below 150 nm. The micelles exhibited thermo-dependent size change, with low critical solution temperature of about 33–35 °C. The characteristic parameters were affected by the composition ratios, length of PNIPAM blocks, and molecular architectures. The camptothecin release demonstrated that the drug release was thermo-responsive, accompanied by the temperature-induced structural changes of the micelles. MTT assays were performed to evaluate the biocompatibility or cytotoxicity of the prepared copolymer micelles.