Reverse thermo-responsive poly(ethylene oxide) and poly(propylene oxide) multiblock copolymers

Aiming at developing new reverse thermo-responsive polymers, poly(ethylene oxide)-poly(propylene oxide) multiblock copolymers were synthesized by covalently binding the two components using carbonyl chloride and diacyl chlorides as the coupling molecules. The appropriate selection of the various components allowed the generation of systems displaying much enhanced rheological properties. For example, 15 wt% aqueous solutions of an alternating poly(ether-carbonate) comprising PEO6000 and PPO3000 segments, achieved a viscosity of 140,000 Pas, while the commercially available Pluronic F127 displayed 5,000 Pas only. Furthermore, the structure of the chain extender played a key role in determining the sol-gel transition. While poly(ether-ester)s containing therephtaloyl (para) and isophtaloyl (metha) coupling units failed to gel at any concentration, a 15 wt% aqueous solution of the polymer chain-extended with phtaloyl chloride (ortho) gelled at 43 degrees C. The water solutions were also studied by dynamic light scattering and a clear influence of the PEO/PPO ratio on the aggregate size was observed. By incorporating short aliphatic oligoesters into the backbone, prior to the chain extension stage, reverse thermal gelation-displaying biodegradable poly(ether-ester-carbonate)s, were generated.     

Melting behavior of hydrolyzable poly(oxyethylene)/poly(L-lactide) copolymers

The melting behavior of poly(oxyethylene) (PEG)/poly(L-lactide) (PLLA) triblock copolymers with PEG contents ≦18,3 wt.-% was studied by differential scanning calorimetry and polarizing optical microscopy. The influence of the PEG segment contents and the hydrolysis of the PEG/PLLA copolymers on the melting process was investigated. The melting temperatures of the PLLA homopolymers decrease with increasing hydrolysis time up to 600 h, and the degree of crystallinity increases from 46 to 56%. This causes the arrangement of the chains more ordered. Therefore, the entropies of fusion (ΔS_m) of the PLLA homopolymers increase during the hydrolysis time up to 600 h. The melting temperatures of the PEG/PLLA copolymers decrease, while the recrystallization temperatures increase with increasing hydrolysis time up to 600 h. In addition, both the increases of PEG content and hydrolysis time of the PEG/PLLA copolymers cause a decrease of ΔS_m. The PEG segments and the hydrolysis are responsible for the disordered arrangement of the chains.     

Graft copolymers of poly(methyl methacrylate) and polythiophene

2-(2-Thienyl)ethyl methacrylate (2TEMA, 1 ), 2-(3-thienyl)ethyl methacrylate (3TEMA,2) and 2-(N-pyrrolyl)ethyl methacrylate (PEMA, 3 ) were synthesized and copolymerized with methyl methacrylate (MMA) by radical initiation with AIBN. The reactivity ratios for the system MMA/2TEMA were determined to be r_MMA = 0,57 ± 0,09 and r_2TEMA = 0,90 ± 0,03. Thiophen was grafted into the copolymers from 1 – 3 via oxidative polymerization in nitromethane. The graft copolymers were soluble as aggregates, and films cast from these solutions reached conductivities in the range of 0,2 to 0,4 S/cm.     

Biodegradable poly(ethylene oxide)/poly(epsilon-caprolactone) multiblock copolymers.

A series of poly(ethylene oxide) (PEO)/poly(epsilon-caprolactone) (PCL) containing biodegradable poly(ether ester urethane)s, covering a wide range of compositions, were synthesized and characterized. The synthesis consisted of a two-step process. During the first step, the ring-opening reaction of epsilon-caprolactone was carried out, initiated by the hydroxyl terminal groups of the PEO chain. The second step involved the chain extension of these PCL-PEO-PCL trimers with hexamethylene diisocyanate. By varying either the ethylene oxide/epsilon-caprolactone ratio or the length of both segments, we obtained a series of polymers having different morphologies and displaying a broad range of properties.     

Synthesis and characterization of poly(ethylene oxide) and poly(perfluorohexylethyl methacrylate) containing triblock copolymers

A new series of poly(perfluorohexylethyl methacrylate)‐block‐poly(ethylene oxide)‐block‐poly(perfluorohexylethyl methacrylate), PFMA‐b‐PEO‐b‐PFMA triblock copolymers has been synthesized by atom transfer radical polymerization using bifunctional PEO macroinitiators. The molecular structure of the block copolymers was confirmed by ¹H NMR spectroscopy and SEC. X‐ray scattering studies have been carried out to investigate their bulk properties. SAXS has shown cubic arrangement of spheres (bcc), hexagonally packed cylinders (hpc) and lamellar microdomain formation in the melt of triblock copolymers investigated, depending on composition. Crystallization was, however, found to destroy the ordered melt morphology and imposes a lamellar crystalline structure. WAXS, DSC and polarized light microscopy measurements confirmed the crystallization of PEO segments in block copolymers. Long PFMA blocks were found to have significant effect on PEO crystallization.

Synthesis of triblock copolymers of EO and FMA by ATRP.     

Erosion of biodegradable block copolymers made of poly( -lactic acid) and poly(ethylene glycol)

Biodegradable block copolymers made of poly(ethylene glycol) monomethylether (Me.PEG) and poly( -lactic acid) (PLA) were investigated for their erosion properties. Wide angle X-ray diffraction (WAXD) and differential scanning calorimetry (DSC) investigations prior to erosion revealed that despite the low content of crystallizable Me.PEG of 10%, Me.PEG5-PLA45 is a partially crystalline polymer. The erosion of the polymer was investigated using cylindrical polymer matrix discs with a diameter of 8mm and a height of 1.5mm. WAXD and DSC spectra obtained from eroded polymer matrix discs suggest that both polymer blocks separate completely during erosion. The crystallinity of Me.PEG5-PLA45 was found to increase during erosion, which is probably due to the improved mobility of Me.PEG inside the polymer with a progressive degree of degradation. The erosion kinetics were found to be similar to that of PLA or poly(lactic-co-glycolic acid). During erosion the polymer matrix weight of dried samples remains constant for 11 weeks after which erosion sets in rapidly. From this observation one can conclude that the impact of the relatively small Me.PEG chains on Me.PEGS-PLA45 erosion is not pronounced. This is beneficial for all those applications that require the stability of the polymer matrix and in which the Me.PEG chain is intended to bring about other effects such as the modification of the surface properties of PLA polymers.     

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.     

ABA type block copolymers of poly(monobutyl itaconate) and poly(monocyclohexyl itaconate) with poly(dimethylsiloxane): Synthesis and characterization

Monoesters of itaconic acid (monobutyl itaconate and monocyclohexyl itaconate) were synthesized and used as monomers. Poly(monobutyl itaconate) (PMBI) and poly(monocyclohexyl itaconate) (PMCHI) were prepared by free radical polymerization of these monomers using tert‐butyl hydroperoxide as initiator. Subsequently, ABA type block copolymers where the A block is PMBI or PMCHI and the B block is poly(dimethyl siloxane) (PDMS) were synthesized by free radical polymerization using a macroinitiator (diperoxycarbamate) containing PDMS units. The structural formulae of the products were confirmed by spectral analysis. The molecular weights of the products are not high. Therefore the mechanical and physical properties are rather poor. However, porous structures of copolymers are observed by means of SEM.     

Thermostable block copolymers, 1. Thermotropic poly(ester-imide) block copolymers

New poly(ester-imide) block copolymers were prepared by polycondensation of aminoterminated poly(ester-imide) blocks with molecular weights from 700 to 6 000 with terephthaloyl dichloride, isophthaloyl dichloride, 2,6-naphthalenedicarbonyl dichloride, adipoly dichloride, dichlorodimethylsilane or dichlorotetramethylsiloxane as low-molecular-weight difunctional coupling reagents. The poly(ester-imide) blocks were synthesized from readily accessible monomers. Dependent on block composition, molecular weight of the block (block length) and kind of spacer liquid-crystalline polymers were obtained with high thermal stability and solubility in polar solvents, yielding tough films with good mechanical properties. The formation of thermotropic mesophases required the proper balance between the rigid blocks and the flexible, kinked or “crankshaft” spacers.     

Synthesis and properties of novel block copolymers containing poly(lactic-glycolic acid) and poly(ethyleneglycol) segments

A synthetic process for obtaining high-molecular-weight block copolymers containing poly(lacticglycolic acid) and poly(ethylene glycol) segments has been established. This process involves the reaction of poly(ethylene glycols) with phosgene, followed by polycondensation of the resulting ,ω-bis (chloroformates) with poly(lactic-glycolic acid) oligomers. The copolymers have been characterized for their molecular weight, solubility properties, water absorption and preliminarily thermal behaviour. All evidence points to the conclusion that the process described is a general one, enabling biodegradable polymers to be obtained tailor-made according to specific requirements.     

Photo-iniferter-based thermoresponsive block copolymers composed of poly(ethylene glycol) and poly(N-isopropylacrylamide) and chondrocyte immobilization

A series of thermoresponsive poly(N-isopropylacrylamide) (PNIPAM)-poly(ethylene glycol) (PEG) block copolymers with various PNIPAM contents and copolymer architectures, such as linear, four-armed and eight-armed configurations, were prepared by iniferter-based photopolymerization of dithiocarbamylated PEGs (DC-PEGs) under ultraviolet (UV)-light irradiation. The increase in monomer/DC-PEG feed ratio resulted in an increase in both the molecular weight and PNIPAM content of copolymers. The measurement of the optical transmittances of aqueous solutions of PNIPAM-PEG block copolymers determined the lower critical solution temperatures (LCSTs) of block copolymers, which ranged from 31.3 to 34.0 degrees C. LCST decreased with increasing block length of PNIPAM and with the formation of a branched architecture. Rabbit chondrocytes were immobilized and cultured in a three-dimensional (3D) gel composed of PNIPAM-PEG block copolymer at 37 degrees C. Gels prepared from copolymers with higher PNIPAM contents at higher concentrations appeared to exhibit a minimal decrease in both cell number and cell viability during a 7-day culture. Cell viability dependencies on material and formulation parameters and the potential use of PNIPAM-PEG block copolymers as an in situ formable scaffold for an engineered cartilage tissue were discussed.     

Stereocomplex formation in ABA triblock copolymers of poly(lactide) (A) and poly(ethylene glycol) (B)

Two series of triblock copolymers of poly(ethylene glycol) (PEG, number-average molecular weight M _n = 6000) and poly(L -lactide) (PLLA) or poly(D -lactide) (PDLA) were prepared by ring-opening polymerization of lactide initiated by PEG end groups using stannous octoate as a catalyst, either in refluxing toluene or in the melt at 175°C. The weight percentage of PLA in the polymers varied between 15 and 75 wt.-%. Blends of polymers containing blocks of opposite chirality were prepared by co-precipitation from homogeneous solutions. The melting temperatures of the crystalline PEG and PLA phases strongly depended on the composition of the polymers. The melting temperature of the PLA phase in the blends was approximately 40°C higher than that of the single block copolymers. Stereocomplex formation between blocks of enantiomeric poly(lactides) in PEG/PLA block copolymers was established for the first time. Water uptake of polymeric films prepared by solution casting was solely determined by the PEG content of the film.     

XPS and SSIMS analysis of the surface chemical structure of poly(caprolactone) and poly(beta-hydroxybutyrate-beta-hydroxyvalerate) copolymers

The surface chemical structures of poly(beta-hydroxybutyrate), poly(caprolactone) and poly(beta-hydroxybutyrate-co-beta-hydroxyvalerate) have been analysed using static secondary ion mass spectrometry and X-ray photoelectron spectroscopy. The X-ray photoelectron spectroscopy data confirm the purity of the polyester surfaces and there is close agreement between the stoichiometric and experimentally determined ratios of the peaks and different carbon environments within the C1s envelopes. The static secondary ion mass spectrometry analysis reveals general fragmentation pathways which permit the ready distinction between the different polyesters examined. The differentiation of the different monomer repeat units in the copolymer together with the detection of some ions representative of the random copolymer sequence are also possible in the static secondary ion mass spectrometry analysis.     

Polymer crystallinity and morphology in polysiloxanes. poly(tetramethyl-p-silphenylenesiloxane) and poly(tetramethyl-p-silphenylene/dimethylsiloxane) copolymers

The crystallinities of polysiloxane homo- and copolymers, measured by DSC and checked by X-ray measurements, are presented. A wide range of crystallization conditions and molecular weight fractions were investigated. The morphological implications of crystallinity changes as a function of molecular weight are discussed in regard to other physical parameters. It is concluded that the dependence of crystallinity and X-ray long period on molecular weight is in accord with a defect interface created via chain entanglements primarily, which are trapped during crystallization. The morphology of the specimens directly reflects their preparative history and molecular weight.     

Biodegradable block poly(ester-urethane)s based on poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymers

A series of block poly(ester-urethane)s (abbreviated as PU3/4HB) based on biodegradable poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P3/4HB) segments were synthesized by a facile way of melting polymerization using 1,6-hexamethylene diisocyanate (HDI) as the coupling agent and stannous octanoate (Sn(Oct)(2)) as catalyst, with different 4HB contents and segment lengths. The chemical structure, molecular weight and distribution were systematically characterized by (1)H nuclear magnetic resonance spectrum (NMR), Fourier transform infrared spectroscopy (FTIR) and gel permeation chromatography (GPC). The thermal property was studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The hydrophilicity was investigated by static contact angle of deionized water and CH(2)I(2). DSC curves revealed that the PU3/4HB polyurethanes have their T(g) from -25.6?°C to -4.3?°C, and crystallinity from 2.5% to 25.3%, being almost amorphous to semi-crystalline. The obtained PU3/4HBs are hydrophobic (water contact angle 77.4°-95.9°), and their surface free energy (SFE) were studied. The morphology of platelets adhered on the polyurethane film observed by scanning electron microscope (SEM) showed that platelets were activated on the PU3/4HB films which would lead to blood coagulation. The lactate dehydrogenase (LDH) assay revealed that the PU3/4HBs displayed higher platelet adhesion property than raw materials and biodegradable polymer polylactic acid (PLA) and would be potential hemostatic materials. Crystallinity degree, hydrophobicity, surface free energy and urethane linkage content play important roles in affecting the LDH activity and hence the platelet adhesion. CCK-8 assay showed that the PU3/4HB is non-toxic and well for cell growth and proliferation of mouse fibroblast L929. It showed that the hydrophobicity is an important factor for cell growth while 3HB content of the PU3/4HB is important for the cell proliferation. Through changing the composition and the chain-length of P3/4HB-diol prepolymers, the biocompatibility of the poly(ester-urethane)s can be tailored.     

In vivo and in vitro degradation of poly(ether ester) block copolymers based on poly(ethylene glycol) and poly(butylene terephthalate)

Two in vivo degradation studies were performed on segmented poly(ether ester)s based on polyethylene glycol (PEG) and poly(butylene terephthalate) (PBT) (PEOT/PBT). In a first series of experiments, the in vivo degradation of melt-pressed discs of different copolymer compositions were followed up for 24 weeks after subcutaneous implantation in rats. The second series of experiments aimed to simulate long-term in vivo degradation. For this, PEOT/PBT samples were pre-degraded in phosphate buffer saline (PBS) at 100 degrees C and subsequently implanted. In both series, explanted materials were characterized by intrinsic viscosity measurements, mass loss, proton nuclear magnetic resonance spectroscopy (1H-NMR) and differential scanning calorimetry (DSC). In both studies the copolymer with the higher PEO content degraded the fastest, although all materials degraded relatively slowly. To determine the nature of the degradation products formed during hydrolysis of the copolymers, 1000 PEOT71PBT29 (a copolymer based on PEG with a molecular weight of 1000 g/mol and 71 wt% of PEO-containing soft segments) was degraded in vitro at 100 degrees C in phosphate buffer saline (PBS) during 14 days. The degradation products present in PBS were analyzed by 1H-NMR and high performance liquid chromatography/mass spectroscopy (HPLC/MS). These degradation products consisted of a fraction with high contents of PEO that was soluble in PBS and a PEOT/PBT fraction that was insoluble at room temperature. From the different in vitro and in vivo degradation experiments performed, it can be concluded that PEOT/PBT degradation is a slow process and generates insoluble polymeric residues with high PBT contents.     

New poly(ester-carbonate) multi-block copolymers based on poly(lactic-glycolic acid) and poly(ϵ-caprolactone) segments

A new family of multi-block copolymers having the structure of poly(ester-carbonate)s was obtained by a chain-extension reaction involving poly(lactic-glycolic acid) oligomers (PLGA) and oligomeric α,ω-bishydroxy-terminated poly(ϵ-caprolactone)s (PCDT). The latter were first transformed into α,ω-bis(chloroformate)s, which were subsequently condensed in the presence of amines with both the hydroxylic and the carboxylic end-groups of PLGA oligomers. Several samples differing in the length of the PCDT segments and in the composition of the PLGA segments were prepared and characterized for their physico-chemical properties. All of them had high molecular weight, good solubility in organic solvents, and modest swellability in aqueous media. As regards their thermal behaviour, some samples showed evidence of the presence of a crystalline phase. Since these products are potentially useful as bioerodible materials in drug delivery systems, some preliminary results on their degradation behaviour under conditions mimicking those found in biological fluids are reported.     

Biocompatibility of poly(epsilon-caprolactone)/poly(ethylene glycol) diblock copolymers with nanophase separation

In this study, we prepared diblock copolymers of poly(epsilon-caprolactone) (PCL) and poly(ethylene glycol) (PEG) by aluminum alkoxide catalysts. The biological responses to the spin cast surface of different PCL/PEG diblock copolymers were investigated in vitro. Our results showed that surface hydrophilicity improved with the increased PEG segments in diblock copolymers and that bacteria adhesion was inhibited by increased PEG contents. PCL-PEG 23:77 showed nanotopography on the surface. The number of adhered endothelial cells, platelets and monocytes on diblock copolymer surfaces was inhibited in PCL-PEG 77:23 and enhanced in PCL-PEG 23:77. Nevertheless, the platelet and monocyte activation on PCL-PEG 23:77 was reduced. PCL-PEG 23:77 had better cellular response as well as lower degree of platelet and monocyte activation. The current study was the first one to demonstrate that surface nanotopography could influence not only cell adhesion and growth but also platelet and monocyte activation.     

Crystalline and dynamic mechanical behaviors of synthesized poly(sebacic anhydride-co-ethylene glycol)

A novel biomaterial: poly(sebacic anhydride-co-ethylene glycol) was synthesized by introducing poly(ethylene glycol) (PEG) into a polyanhydride system. This copolymer was synthesized using sebacic acid and PEG via melt-condensation polymerization. The crystalline behavior of these synthesized products was studied, and compared to that of polymer blends of poly(sebacic anhydride) (PSA) and PEG. The crystallinity of PSA chain segments can be significantly enhanced by increasing chain mobility via the introduction of PEG. The crystallinity of the PSA component in copolymers was substantially greater than that of blends. However, the crystalline growth of the PEG segments was totally hindered by the presence of PSA chain segments, such that no crystal for PEG component was found in these copolymers. Besides, a dynamic mechanical analysis of these materials was also performed to provide additional information concerning visco-elastic behavior for other biomedical applications, where it was found that the viscous behavior in copolymers was more significant than in neat PSA and PEG.     

A convenient route to poly(methylphenylsilane)-graft-polystyrene copolymers

A graft copolymer of polystyrene on poly(methylphenylsilylene) was conveniently synthesised by using the bromomethyl groups of bromomethylated poly(methylphenylsilylene) as initiating sites for the bulk polymerisation of styrene by an atom transfer radical mechanism.