pH/temperature-sensitive 4-arm poly(ethylene glycol)-poly(amino urethane) copolymer hydrogels

A series of novel pH/temperature-sensitive 4-arm poly(ethylene glycol)-poly(amino urethane) copolymers was synthesized via addition polymerization. The resulting copolymers were characterized by ¹H, ¹³C NMR, Fourier transform infrared spectroscopy and gel permeation chromatography. Poly(amino urethane) (PAU) segment acts as a pH/temperature-sensitive block. The copolymer aqueous solutions showed a sol-to-gel-to-aggregation phase transition as a function of pH and temperature when the pH of the copolymer solution is higher than 6.8. The sol-gel phase transition could be controlled by varying the PAU block length and copolymer concentration. The gel window covers the physiological conditions and a white gel was formed rapidly after subcutaneously injecting the copolymer solution (30 wt%) into SD rats. The in vitro release of chlorambucil, an anticancer drug, was sustained over 14 days under physiological conditions.     

pH- and temperature-sensitive multiblock copolymer hydrogels composed of poly(ethylene glycol) and poly(amino urethane)

A series of novel pH- and temperature-responsive multiblock copolymers (poly(PEG/HEP urethane)) consisting of poly(ethylene glycol) (PEG) and poly(amino urethane) (PAU) were synthesized, and their physicochemical properties were studied. The amphiphilic block copolymers were synthesized from PEG, 1,4-bis(hydroxyethyl) piperazine (HEP) and 1,6-diisocyanato hexamethylene (HDI) in the presence of dibutyltin dilaurate as a catalyst. The resulting polymers were examined by FT-IR, ¹H and ¹³C NMR spectroscopies and gel permeation chromatography (GPC). The solution properties of the copolymers were studied by turbidity measurement and fluorescence spectroscopy. The copolymers showed a pH-dependent soluble-insoluble transition in diluted aqueous solutions. The concentrated polymer solutions exhibited a thermo-induced sol-gel-sol phase transition at pH 6.8-7.4. The gel window covers the physiological conditions. After a subcutaneous injection of the multiblock copolymer solution into mice, a transparent and soft gel was formed immediately. The in vitro release of a model anticancer drug, chlorambucil, persisted over 2 weeks under physiological conditions.     

Synthesis and characterization of poly(amino urea urethane)-based block copolymer and its potential application as injectable pH/temperature-sensitive hydrogel for protein carrier

A series of novel block copolymer comprising of poly(ethylene glycol) (PEG) and poly(amino urea urethane) (PAUU) was simply synthesized and characterized. The block copolymers were synthesized by a polyaddition reaction between isocyanate groups of 1,6-diisocyanato hexamethylene with secondary amine and hydroxyl groups of 2-hydroxyethyl piperazine and hydroxyl groups at the ends of PEG in chloroform in the presence of dibutyltin dilaurate as a catalyst and characterized by ¹H and ¹³C NMR, FTIR and gel permeation chromatography. Copolymer aqueous solutions exhibited pH/temperature-dependent sol–gel phase transitions with a sol-to-gel and a gel-to-sol phase transition corresponding to the increasing of pH and temperature, respectively, with low concentrations. The gel regions covered the physiological condition and could be modulated by changing PAUU fraction, molecular weight of PEG and copolymer concentration. The copolymer hydrogel did not show cytotoxicity. After injecting the copolymer solution subcutaneously into SD rats, an in situ gel formed rapidly. The copolymer hydrogel was confirmed as a protein depot carrier; it showed a sustained release of FITC-BSA over 6 weeks. This novel pH/temperature-sensitive hydrogel system is a potential applicable candidate for protein carrier.     

Synthesis and characterization of multiblock semi-crystalline hydrophobic poly(ether ether ketone)–hydrophilic disulfonated poly(arylene ether sulfone) copolymers for proton exchange membranes

Multiblock copolymers based on alternating segments of telechelic phenoxide terminated hydrophilic fully disulfonated poly(arylene ether sulfone) (BPS100) and decafluorobiphenyl (DFBP) terminated hydrophobic poly(arylene ether ketimine) (PEEKt), were synthesized from the hydrophilic and ketimine-protected amorphous hydrophobic telechelic oligomers by nucleophilic coupling reactions. After film formation from DMSO, the copolymer was acidified, which converted the ketimine to semi-crystalline ketone segments and the sulfonate salts to disulfonic acids. A semi-crystalline phase with a T_m of 325 °C was confirmed. The semi-crystalline multiblock copolymer membranes were tough, ductile and solvent resistant. Fundamental properties as proton exchange membranes (PEMs) showed enhanced conductivities under fully hydrated and reduced humidity conditions. These multiblock copolymers exhibited low in-plane anisotropic swelling behavior, in contrast to the random copolymers.     

pH-sensitive and bioadhesive poly(β-amino ester)-poly(ethylene glycol)-poly(β-amino ester) triblock copolymer hydrogels with potential for drug delivery in oral mucosal surfaces

A series of novel pH-sensitive triblock copolymers composed of poly(β-amino ester)-poly(ethylene glycol)-poly(β-amino ester) (PAE-PEG-PAE) were synthesized by conjugating poly(β-amino ester) to poly(ethylene glycol). The resulting polymers were characterized by ¹H and ¹³C NMR in CDCl₃ and gel permeation chromatography in tetrahydrofuran. The concentrated polymer solutions (30 wt%) exhibited a gel-to-sol transition in the pH range 6.4-7.8. The gel window spanned physiological conditions (37 °C, pH 7.4). After injection into a rat, the copolymer solution (30 wt%) changed to a gel in a short time. This copolymer hydrogel showed bioadhesive properties and in vitro release of lidocaine was controllable.     

Synthesis of novel ABA triblock and (ABA)n multiblock copolymers comprised of polyisobutylene and poly(γ-benzyl-l-glutamate) segments

The synthesis of ABA triblock copolymers comprised of polyisobutylene (PIB) and poly(γ-benzyl-l-glutamate) (PBLG) segments has been demonstrated for the first time by the polymerization of γ-benzyl-l-glutamate N-carboxyanhydride (BLG-NCA) initiated with well-defined α,ω-primary amino-functional PIBs. The ammonium-mediated polymerization of BLG-NCA provided better control of molecular weights and lower polydispersity indices (PDIs) compared to the conventional polymerization. The compositional homogeneity of the block copolymers has been confirmed by GPC-MALLS and ¹H NMR spectroscopy. Since the resulting ABA triblock copolymer possessed primary amino groups at α,ω-ends, further extension reaction with 4,4′-methylene-bis(phenyldiisocyanate) was possible to afford a novel (ABA)_n multiblock copolymer.     

Electrochemical copolymerization of aniline with m-aminophenol and novel electrical properties of the copolymer in the wide pH range

A copolymer, poly(aniline-co-m-aminophenol), has been synthesized using repeated potential cycling. The monomer concentration ratio, acid concentration and applied potential strongly affect the copolymerization rate and the properties of the copolymer. The optimum conditions for the copolymerization are that the scan potential range is controlled between −0.10 and 0.95 V (vs.SCE), and a solution consists of 0.34 M aniline, 0.012 M m-aminophenol and 2 M H₂SO₄. The IR spectra of the copolymers demonstrate that the m-aminophenol units are included in the copolymer chains. The cyclic voltammograms of the copolymers in 0.3 M Na₂SO₄ solution with various pH values were performed at the potential ranges from −0.20 to 0.80 V and at a scan rate of 60 mV s⁻¹. The results indicate that the copolymer still hold 41.7% of the electrochemical activity when the copolymer electrode was transferred from a solution of pH 5.0 to a solution of pH 11.0 in the potential range of −0.20 to 0.80 V. An impedance plot of the copolymer in a solution with pH 12.0 and at 0.40 V is constructed of a semicircle and a Warburg line with a slope of 1. This means that the electrode reaction of the copolymer at pH 12.0 is also under mass transfer control. The conductivity of the copolymer prepared under the optimum conditions is 1.42 S cm⁻¹, and slightly depends on the pH value. Thus, the pH dependence of the electrical properties of the copolymer is improved compared with poly(aniline-co-o-aminophenol), and is much better than that of the parent polyaniline.     

Facile synthesis of multiblock copolymers composed of poly(tetramethylene oxide) and polystyrene using living free-radical polymerization macroinitiator

A facile synthetic strategy for well-defined multiblock copolymers utilizing ‘living’ free-radical polymerization macroinitiator has been presented. Polyurethane composed of alkoxyamine initiating units and poly(tetramethylene oxide) (PTMO) segments was prepared by polyaddition of tolylene 2,4-diisocyanate terminated PTMO with an alkoxyamine-based diol. Polymerization of styrene with the polyurethane macroinitiator was carried out under nitroxide-mediated free-radical polymerization (NMRP) condition. GPC, NMR, and IR data revealed that the polymerization was accurately controlled and well-defined polystyrene chains were inserted in the main chain of macroinitiator to give the poly(tetramethylene oxide)-b-polystyrene multiblock copolymers. The synthesized multiblock copolymers were characterized by tensile test, differential scanning calorimetry, and dynamic mechanical analysis. Mechanical properties of the multiblock copolymers can be tuned by the sufficient molecular weight control of PS chains. Soft segment of PTMO and hard segment of PS were apparently compatible due to the multiblock structure of low molecular weight segments and polar urethane groups.     

Electrochemical copolymerization of m-toluidine and o-phenylenediamine

Electroactive copolymers of m-toluidine (MT) and o-phenylenediamine (OPD) were prepared electrochemically in aqueous sulfuric acid by potential cycling and characterized with cyclic voltametry, in situ conductivity measurements and FT-IR spectroscopy. The voltammograms of the copolymers exhibit different behavior for different concentrations of OPD in the comonomer feed. At optimum conditions the resulting poly(OPD-co-MT) shows an extended useful potential range of the redox activity as compared to the corresponding homopolymers. The effect of scan rate and pH on the electrochemical activity was studied. The copolymer was electrochemically active even at pH 8.0. The stability of the copolymer film was also tested. The copolymer has a potential region of maximum conductivity different from that of PMT and POPD. The conductivity of the copolymer is between the conductivity of the homopolymers. The vibrational bands at 3122/3450 and 2922/875 cm⁻¹ in the FT-IR spectra of the copolymer indicate the presence of both OPD and MT units, respectively, in the copolymer backbone.     

Biodegradable and photocurable multiblock copolymers with shape‐memory properties from poly(ε‐caprolactone) diol,poly(ethylene glycol), and 5‐cinnamoyloxyisophthalic acid

Biodegradable and photocurable multiblock copolymers of various compositions were synthesized by the high‐temperature solution polycondensation of poly(ε‐caprolactone) (PCL) diols of molecular weight (M_n) = 3000 and poly(ethylene glycol)s (PEG) of M_n = 3000 with a dichloride of 5‐cinnamoyloxyisophthalic acid (ICA) as a chain extender, followed by irradiation by a 400 W high‐pressure mercury lamp (λ > 280 nm) to form a network structure. The gel contents increased with photocuring time, reaching a level of over 90% after 10 min for all copolymers without a photoinitiator. The thermal and mechanical properties of the photocured copolymers were examined by DSC and tensile tests. In cyclic thermomechanical tensile tests, the photocured ICA/PCL/PEG copolymer films showed good shape‐memory properties at 37–60°C, with both shape fixity ratio and shape recovery ratio over 90% at a maximum tensile strain of 100–300%. The water absorption of these copolymers and their rate of degradation in a phosphate buffer solution (pH 7.0) at 37°C increased significantly with increasing PEG content. The novel photocured ICA/PCL/PEG multiblock copolymers are potentially useful in biomedical applications. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Novel amphiphilic poly(ester‐urethane)s based on poly[(R)‐3‐hydroxyalkanoate]: synthesis,biocompatibility and aggregation in aqueous solution

BACKGROUND: The aim of this work was to develop polyhydroxyalkanoates (PHAs) for blood contact applications, and to study their self‐assembly behavior in aqueous solution when the PHAs are incorporated with hydrophilic segments. To do this, poly(ester‐urethane) (PU) multiblock copolymers were prepared from hydroxyl‐terminated poly(ethylene glycol) (PEG) and hydroxylated poly[(R)‐3‐hydroxyalkanoate] (PHA‐diol) using 1,6‐hexamethylene diisocyanate as a coupling reagent. The PEG segment functions as a soft, hydrophilic and crystalline portion and the poly[(R)‐3‐hydroxybutyrate] segment behaves as a hard, hydrophobic and crystalline portion. In another series of PU multiblock copolymers, crystalline PEG and completely amorphous poly[((R)‐3‐hydroxybutyrate)‐co‐(4‐hydroxybutyrate)] behaved as hydrophobic and hydrophilic segments, respectively. RESULTS: The formation of a PU series of block copolymers was confirmed by NMR, gel permeation chromatography and infrared analyses. The thermal properties showed enhanced thermal stability with semi‐crystalline morphology via incorporation of PEG. Interestingly, the changes of the hydrophilic/hydrophobic ratio led to different formations in oil‐in‐water emulsion and surface patterning behavior when cast into films. Blood compatibility was also increased with increasing PEG content compared with PHA‐only polymers. CONCLUSION: For the first time, PHA‐based PU block copolymers have been investigated in terms of their blood compatibility and aggregation behavior in aqueous solution. Novel amphiphilic materials with good biocompatibility for possible blood contact applications with hydrogel properties were obtained. Copyright © 2008 Society of Chemical Industry     

Multiblock terephthalate copolymer as impact modifier for poly(propylene)/poly(butylene terephthalate) blends

The melt polycondensation method was investigated for the synthesis of a multiblock copolymer. The copolymer consisted of hard segments of poly(butylene terephthalate) (PBT) and soft segments of dimerised fatty acid. This multiblock copolymer was characterised by ¹H and ¹³C NMR and FTIR spectroscopies and differential scanning calorimetry. The ¹H NMR method was used for estimating quantitatively the amount of the hard/soft segments. The polymer morphology was characterised using light microscopy and transmission electron microscopy. The investigated polymer was used in a small amount as an additive to poly(propylene)/PBT blends in order to evaluate its influence on the morphology and impact properties of these blends.     

Degradable micelles based on hydrolytically degradable amphiphilic graft copolymers for doxorubicin delivery

Micelles based on a low-toxic and hydrolytically degradable poly(β-amino ester)-g-octadecyl acrylate (PAE-g-ODA) amphiphilic copolymer were developed for doxorubicin (DOX) delivery. A two-step reaction pathway was used to synthesize PAE-g-ODA copolymers with poly(ethylene glycol) segments in the backbone via Michael-type addition reaction. Copolymers with various grafting degrees were obtained by tuning the feeding molar ratios of acrylate/formed secondary amine and the grafting reaction time. Among this series of copolymers, PAE-g-ODA-2 (PAE-g-ODA with 45% ODA side chains) were found to form spherical micelles with an average size of 72.5 nm, as determined by dynamic light scattering (DLS) and transmission electron microscope (TEM), whereas the other PAE-g-ODA copolymers fail to form stable micelles with a narrow size distribution in an aqueous solution. The titration curve illustrated that PAE-g-ODA-2 has a high buffer capacity in the pH range of 7.5-5. The hydrolytic degradation of PAE-g-ODA-2 copolymer in PBS buffer (pH 7.4, 37 °C) was monitored by ¹H NMR. It was found that up to 70% ester groups in the backbones were hydrolyzed in 48 h. The DOX-loaded micelles release about 70% trapped DOX within 48 h in physiological condition. Cytotoxicity assay showed a low cytotoxicity of PAE-g-ODA-2 micelles as well as a higher inhibition against HepG2 tumor cells of DOX-loaded micelles than free DOX.     

Synthesis,characterization, and properties of two‐component amphiphilic polyoxyethylene–containing multiblock copolymers

Amphiphilic (oxyethylene–oxypropylene) and (oxyethylene–styrene) multiblock copolymers, both with high molecular weights, were synthesized by coupling poly(ethylene glycol) (PEG) with poly(propylene glycol) (PPG) or with telechelic dihydroxy polystyrene using 2,4‐toluene diisocyanate as a coupling agent, respectively. The polymerization conditions were investigated. The products were purified and characterized by IR, ¹H‐NMR spectroscopy, and membrane osmometry and identified as multiblock copolymers. Crystallinity of the two kinds of multiblock copolymers was determined by DSC. They showed good emulsifying properties. Their complexes with LiClO₄ showed high room‐temperature conductivities from 3 × 10⁻⁵ to 4 × 10⁻⁴ S/cm at 30°C. High molecular weight (oxyethylene–oxypropylene) multiblock copolymers, at a weight ratio of PEG/PPG = 6/4, behave like thermoplastic elastomers. The (oxyethylene–styrene) copolymer functions as a good compatibilizer for the blend of chlorohydrin rubber and polystyrene. An amount of only 3 wt %, based on the blend, is needed to increase the tensile strength of the blend almost sixfold. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 95: 1295–1301, 2005     

A novel biodegradable poly(p-dioxanone)-grafted poly(vinyl alcohol) copolymer with a controllable in vitro degradation

A novel biodegradable copolymer was synthesized from poly(vinyl alcohol) and poly(p-dioxanone) by ring-opening polymerization. The molecular structure of the copolymer was characterized by one- and two-dimensional NMR spectroscopy. The results of differential scanning calorimetry (DSC) show that the amphiphilic and comb grafted structure of the copolymer make its crystalline behavior different from that of the poly(p-dioxanone) homopolymer (PPDO). The in vitro degradation rate of the copolymers can be controlled via adjusting the number and length of PPDO segments of PVA-g-PPDO copolymers. The copolymer has a potential application in biomedical materials or in the controlled release of drug.     

Effect of multiblock copolymers in polymer blends

The use of multiblock copolymers for the compatibilization of immiscible polymer blends is controversially discussed in the literature. Investigations have been carried out to estimate the effect of multiblock copolymers containing segments of a liquid crystalline polyester (LCP) and polysulfone (PSU) segments in blends of the based homopolymers. One goal was to determine whether multiblock copolymers provide an opportunity for compatibilizing PSU/LCP blends. By using PSU/LCP multiblock copolymers with different molecular weights of the blocks in the appropriate binary, solution-casted blends, it was shown that the interpenetration of the polysulfone phase of the block copolymer and the PSU matrix leads to an improved miscibility of the blend. This effect is retained in ternary blends of PSU, LCP, and the multiblock copolymer, assuming a certain critical molecular weight of the multiblock copolymer segments. In addition, some mechanical characteristics of PSU/LCP melt blends such as the E-modulus and fracture strength are improved by adding long-segmented multiblock copolymers. © 1997 John Wiley & Sons, Inc. J Appl Polym Sci 66: 2293–2309, 1997     

Synthesis and properties of ABA-type triblock copolymers of poly(glycolide-co-caprolactone) (A) and poly(ethylene glycol) (B)

Poly(glycolide-co-caprolactone) (A)-poly(ethylene glycol) (B) ABA-type triblock copolymers (PGCE) were synthesized by bulk ring opening polymerization, using the hydroxyl endgroups of poly(ethylene glycol) (PEG) as initiator and stannous octoate as catalyst. The resulting copolymers were characterized by various analytical techniques. Gel permeation chromatographic analysis indicated that the polymerization product was free of residual monomers, PEG and oligomers. ¹H NMR and differential scanning calorimeter results demonstrated that the copolymers had a structure of poly(glycolide-co-caprolactone) (PGC) chains chemically attached to PEG segments. All the PGCE copolymers showed improved hydrophilicity in comparison with the corresponding PGC copolymers with the same molar ratio of glycolidyl and caproyl units. The microspheres of PGCE copolymer exhibited rough surfaces quite different from the smooth surface of PGC microspheres. This phenomenon was attentively ascribed to the highly swollen ability of PGCE copolymers and the freeze-drying process in the microspheres fabrication.     

Synthesis and characterization of novel functionalized polylactides with pendent hydroxyl arms

A class of polyesters have been synthesized by the ring-opening copolymerization of dl-lactide (DLLA) and RS-benzyloxyethyl-β-malolactonate (MABE) using different monomer feeding doses. The compositions and structures of poly(dl-lactide-co-RS-benzyloxyethyl-β-malolactonate) (poly(DLLA-co-MABE)) were determined by ¹H and ¹³C NMR measurements. GPC measurement showed that the molecular weight of the copolymers decreased as the MABE content increases. After catalytic hydrogenation of the benzyl ether functions, the desired copolymers with pendent hydroxyl arms, poly(dl-lactide-co-RS-hydroxyethyl-β-malolactonate) (poly(DLLA-co-MAHE)), were recovered. Thermal properties of poly(DLLA-co-MABE) and poly(DLLA-co-MAHE) copolymers were examined by differential scanning calorimetry (DSC) measurement. Single glass transition temperature appeared in the DSC spectra, which confirmed that the copolymers were true copolymers and not blends. The hydrophilicity of poly(DLLA-co-MAHE) copolymer was tunable, which increased with the increase in MAHE content. Furthermore, the hydrolytic degradation of poly(DLLA-co-MAHE) material was investigated and the results showed that faster degradation was observed in the copolymer film containing more MAHE content.     

Enzyme-catalyzed polymerization and degradation of copolymers prepared from ?-caprolactone and poly(ethylene glycol)

Copolymerizations of ?-caprolactone (CL) with monohydroxyl or dihydroxyl poly(ethylene glycol) (PEG) were successfully performed using Novozyme-435 (immobilized lipase B from Candida antartica) as catalyst. Diblock and triblock copolymers with different compositions were characterized by ¹H NMR, GPC, DSC and X-ray diffraction. The enzymatic copolymerization carried out in toluene presented higher reaction rate and yield than that in bulk. Increasing the [CL]/[EO] feed ratio resulted in increases of molecular weight (M_n) of copolymers. Moreover, the compositions of triblock copolymers were closer to the monomer feed ratios than those of diblock copolymers. The resulting copolymers were all semicrystalline, the crystalline structure being of the PCL type. Solution cast films were allowed to degrade in a pH 7.0 phosphate buffer solution containing Pseudomonas lipase. Weight loss data showed that the introduction of PEG segments to the PCL main chain did not alter the enzymatic degradation of PCL significantly.     

Aggregation of biodegradable amphiphilic poly(succinimide-co-N-propyl aspartamide) and poly(N-dodecyl aspartamide-co-N-propyl aspartamide) in aqueous medium and its preliminary drug-released properties

Two series of biodegradable amphiphilic copolymers, poly(succinimide-co-N-propyl aspartamide) (PSI-PA) and poly(N-dodecyl aspartamide-co-N-propyl aspartamide) (PDDA-PA) were synthesized by partial and total aminolysis of polysuccinimide (PSI), respectively. PSI-PA copolymers could self-aggregate in water directly under ultrasonication at room temperature. Differing from PSI-PA copolymers, the aggregates of PDDA-PA need to add PDDA-PA DMF solution into an excessive amount of water. The aggregative properties of PSI-PA and PDDA-PA copolymers have been investigated by dynamic light scattering (DLS) and surface tension measurements. Hydrophilicity of these two copolymers was attributed to the N-propyl aspartamide segments. Due to the stiff structure, succinimide segments preferred to form irregular hydrophobic microdomains, and some aggregates of PSI-PA are bimodal size distribution in water medium, while the more flexible PDDA-PA copolymer chains preferred to form monodispersed spherical aggregates. Elevated temperature could reduce the aggregate size of both PSI-PA and PDDA-PA copolymers due to the breaking of the hydrogen bonding and the releasing of the bonded water molecules. PSI-PA copolymers were surface active, while the surface tension of PDDA-PA copolymers was independent on concentration. The drug-loaded aggregates of PSI-PA also have been prepared and the preliminary release properties have been studied in vitro.