Structure and properties of segmented poly(ether ester)s and polyurethanes, 5. Synthesis of uniform oligo(oxytetramethylene)s

The synthesis of a series of homologous α-hydro-ω-hydroxyoligo(oxytetramethylene)s, of the corresponding bis(phenylurethane)s, and of α-hydro-ω-chlorooligo(oxytetramethylene)s is described. The purity of the individual oligomers was characterized by gel permeation chromatography and their melting behaviour was investigated. A value of 45 ± 2°C is derived as the equilibrium melting point of poly(oxytetramethylene) from a suitable extrapolation of the melting point of the oligomers to infinite molecular weight.     

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.     

Functional polymers and sequential copolymers by phase transfer catalysis, 2. Synthesis and characterization of aromatic poly(ether-sulfone)s containing vinylbenzyl and ethynylbenzyl chain ends

A simple method for the synthesis of α,ω-bis(vinylbenzyl) aromatic poly(ether-sulfone)s ( 2 ) and their transformation into α,ω-bis(ethynylbenzyl) aromatic poly(ether-sulfone)s ( 4 ) is presented. This method involves a fast and quantitative Williamson etherification of the α,ω-bis(hydroxyphenyl)polysulfone with a mixture of p- and m-chloromethylstyrenes in the presence of tetrabutylammonium hydrogen sulfate as phase transfer catalyst, a subsequent bromination, and then a dehydrobromination with potassium tert-butoxide. The DSC study of the thermal curing of these α,ω-bis(vinylbenzyl)polysulfones and α,ω-bis(ethynylbenzyl)polysulfones demonstrates high thermal reactivity for this new class of styrene-terminated oligomers.     

Multiblock poly(ether-ester-amide)s based on polyamide-6 and poly(ethylene glycol), 2 Effect of composition and soft-segment length on the structure of poly(ether-ester-amide)s as revealed by X-ray scattering

Isotropic unannealed and annealed melt-pressed and quenched samples of segmented multiblock poly(ether-ester-amide)s based on polyamide-6 and poly(ethylene glycol)s (PEGs) of molecular weights 400 and 1000 with various hard/soft segment weight ratios were investigated. The effect of composition, segment length and annealing temperature on the crystal structure was studied by differential scanning calorimetry, wide-angle and small-angle X-ray scattering. In addition to the γ-phase, one of the unannealed samples having relatively long hard and soft segments exhibits a high amount of α-phase. This is assumed to be due to the high flexibility of the PEG segments, linking the polyamide blocks thus enhancing their mobility. The lack of hydrogen bonds between the PEG segments facilitates crystallization of the polyamide segments in the more perfect α-modification, which is the most pronounced in the above mentioned sample. Part of the α-phase transforms into the α-phase upon annealing in all copolymer samples studied, similarly to polyamide-6.     

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.     

Functional poly[(ethylene oxide)-co-(β-benzyl-L-aspartate)] polymeric micelles: block copolymer synthesis and micelles formation

Well-defined α-methoxy-ω-amino and α-hydroxy-ω-amino poly(ethylene oxides) (PEOs), obtained by chemical modifications of α-hydroxy-ω-amino PEO, were studied for block copolymerization with β-benzyl-L -aspartate-N-carboxy anhydride (BLA-NCA); the block copolymers were obtained via polymerization of BLA-NCA with the primary amino end-groups of the PEOs as initiator in the mixture CHCl₃/N,N-dimethylformamide (DMF) (vol. ratio10/1). Gel-permeation chromatography (GPC) of both block copolymers showed the presence of BLA oligomers. α-Methoxy PEO/PBLA and α-hydroxy PEO/PBLA block copolymers were submitted to selective precipitation in 2-propanol; this method allowed total elimination of oligomers as shown by GPC of the purified block copolymers. Moreover, for each block copolymer, the number of BLA units determined by ¹H NMR spectroscopy (in CDCl₃) was in good agreement with the number calculated from the ratio BLA-NCA/amino end-groups of PEO. The polymeric micelles having hydroxy functions or methoxy groups on the outer-shell were prepared by dialysis against water of the corresponding solution of the pure block copolymers. These polymeric micelles were characterized by dynamic light scattering (diameter) and by fluorescence spectroscopy (critical micellar concentration, cmc) using pyrene as a fluorescence probe. Both polymeric micelles have a small diameter (<50nm) and a very low cmc (<20 mg/L in water).     

Fluorinated polyurethanes, 1. Synthesis and characterization of fluorine-containing segmented poly(urethane-urea)s

To produce high performance antithrombus elastomers, a series of new fluorine-containing segmented poly(urethane-urea)s was synthesized from 2,2,3,3,4,4,5,5-octafluorohexamethylene diisocyanate ( 1 ) and α-hydro-ω-hydroxypoly(oxyalkylene)s ( 5a, b and 6 ) or fluorinated dioxa-1,10-decanediols ( 3 and 4 ) (as the soft segments) via the prepolymers ( 7 ) which subsequently were reacted with various diamines including a fluorinated aliphatic diamine ( 2 ) as chain-extenders. High-molecular-weight polymers were obtained in high yields with 5a and nonfluorinated diamines. Spectroscopic analysis of the prepolymers and the chain-extended polymers indicated their structures to be highly ordered. Stress-strain curves of films cast from a DMF solution indicated the polymers to be typical elastomers with tensile strength as much as 600–700 kg/cm².     

Poly(Ether/Ester)s based on poly(tetramethylene terephthalate) and poly(ethylene glycol), 3. Effect of thermal treatment and drawing on the structure of the poly(ether/ester)s

Annealed drawn and undrawn bristles of poly(ether/ester)s based on poly(tetramethylene terephthalate) (PTMT) and poly(ethylene glycol) PEG 1000 (in various ratios) are studied by means of small-angle X-ray scatering and differential scanning calorimetry (DSC). The samples with the lowest PTMT content (49 wt.-% PTMT) show on abrupt increase of the scattering intensity and the long spacing with increasing annealing temperature T_a, this increase becoming less pronounced with increasing fraction of hard segment (PTMT). The DSC heating scans are characterized by a low-temperature glass transition due to the soft polyether segments and a multiple melting behaviour at about 200°C due to the crystalline hard PTMT segments. The data suggest a dependence of the thermal behaviour on the chemical composition, annealing temperature, and orientation. The characteristics of the undrawn samples are similar to those of the homopolyester PTMT and the copolymers based on PTMT and poly(tetramethylene oxide). Evidence is found for an increase of phase separation with an increase of the annealing temperature. The formation of larger amorphous regions of PEG with increasing T_a determines the thermal and scattering behaviour observed.     

Influence of electron-beam radiation on the hydrolytic degradation behaviour of poly(lactide-co-glycolide) (PLGA)

The purpose of this study is to examine the effect of electron-beam (e-beam) radiation on the hydrolytic degradation of poly(lactide-co-glycolide) (PLGA) films. PLGA films were irradiated and observed to undergo radiation-induced degradation through chain scission, as observed from a drop in its average molecular weight with radiation dose. Irradiated (5, 10 and 20 Mrad) and non-irradiated (0 Mrad) samples of PLGA were subsequently hydrolytically degraded in phosphate-buffered saline solution at 37.0 degrees C over a span of 12 weeks. It was observed that the natural logarithmic molecular weight (lnMn) of PLGA decreases linearly with hydrolytic degradation time. The rate of water uptake is higher for samples irradiated at higher radiation dose (e.g. 20 Mrad) and subsequently causing an earlier onset of mass loss. It is postulated that the increase in water uptake is due to the presence of more hydrophilic end groups, which results in the formation of microcavities because of an increase in osmotic pressure. A relationship between radiation dose and the rate of hydrolytic degradation of PLGA films, through its molecular weight was also established. This relationship allows a more accurate and precise control of the life span of PLGA through the use of e-beam radiation.     

Synthesis of a new family of poly(amido-amine)s carrying poly(oxyethylene) side chains

A new class of water-soluble poly(amido-amine)s (PAA's) carrying poly(oxyethylene) (PEO) side chains were synthesized following two distinct pathways. The first route consists in the direct stepgrowth polymerization through addition in water of an equimolar amount of α-(2-aminoethyl)-ω-methoxypoly(oxyethylene) (6) of well-defined molecular weight to 1,4-bis(acryloyl)-piperazine (7) . Furthermore, this reaction was performed in the presence of an excess of the bisacrylmonomer 7 , resulting in a new bisacrylic macromonomer (9) of PEO. In the second route this bisadduc 9 was then polymerized with piperazine (10) , yielding a PEO-grafted PAA. The structures of both polymers were characterized by means of ¹H NMR. Viscosity and vapour pressure osmometric measurements revealed that the molecular weights in both cases were fairly low (M?_n ≈ 3 000).     

Biodegradable poly(ether-ester) multiblock copolymers for controlled release applications: An in vivo evaluation

Multiblock poly(ether-ester)s based on poly(ethylene glycol), butylene terephthalate, and butylene succinate segments were evaluated for their in vivo degradation and biocompatibility in order to establish a correlation with previously reported in vitro results. Porous polymer sheets were implanted subcutaneously for 32 weeks in rats. The degradation was monitored visually (histology), by molecular weight (GPC), and by copolymer composition (NMR). Substitution of the aromatic terephthalate units by aliphatic succinate units was shown to accelerate the degradation rate of the copolymers. Direct correlation of the in vivo and in vitro degradation of the porous implants showed a slightly faster initial molecular weight decrease in vivo. Besides hydrolysis, oxidation occurs in vivo due to the presence of radicals produced by inflammatory cells. In addition, the higher molecular weight plateau of the residue found in vivo indicated a higher solubility of the oligomers in the extracellular fluid compared to a phosphate buffer. Minor changes in the poly(ether-ester) compositions were noted due to degradation. Microscopically, fragmentation of the porous implants was observed in time. At later stages of degradation, macrophages were observed phagocytozing small polymer particles. Both in vitro cytotoxicity studies and histology on in vivo samples proved the biocompatibility of the poly(ether-ester)s.     

Heterochain polymers based on natural amino acids. Synthesis and enzymatic hydrolysis of regular poly(ester amide)s based on bis(L-phenylalanine) α,ω-alkylene diesters and adipic acid

Novel biodegradable regular poly(ester amide)s were synthesized by polycondensation of p-toluenesulfonic acid salts of bis(phenylalanine) α,ω-alkylene diesters ( 1 ) with bis(p-nitrophenyl) adipate under mild conditions in organic solvents in the presence of triethyl amine as acid acceptor. Enzymatic hydrolysis (α-chymotrypsinolysis) of the starting salts 1 , the model bis(ester acetamide)s 2 and the obtained poly(ester amide)s 3 was investigated at 37°C and pH 8 using potentiometric titration. It was established that the hydrolysis rate increased with elongation of the α,ω-alkylene chain. A strong noncovalent immobilization of the enzyme on the polymeric surface was observed.     

Enzymatic degradation behavior and mechanism of poly(lactide-co-glycolide) foams by trypsin

The purpose of this study is to investigate the enzymatic degradation behaviors of porous poly(lactide-co-glycolide) (PLGA) foams in the presence of trypsin, in comparison with their hydrolytic degradation. To inspect the effect of trypsin on the degradation of PLGA, both the hydrolytic and enzymatic degradation of non-porous PLGA samples were also performed. The changes of molecular weight and molecular weight distribution (polydispersity) during the degradation were determined by gel permeation chromatograph. And the changes of weight, thickness and morphology with the degradation were also measured. The degradation of PLGA displayed as two stages. In the first stage, the molecular weight of PLGA decreased continuously with degradation time, whereas little weight loss occurred. But in the second stage, the molecular weight of PLGA had decreased to a low value and was almost unchanged with time, while the sample experienced significant weight loss. And it was found that the presence of trypsin could significantly accelerate the weight loss rates of all the PLGA samples, but it caused little difference in the decrease of molecular weight and the change of PLGA composition between the enzymatic and hydrolytic degradation. Therefore, the enzymatic degradation of PLGA was still primarily a hydrolysis process. A mechanism of enzymatic degradation was proposed that the trypsin could enhance the weight loss of PLGA by acting as surfactant to push the dispersion of degradation products into water even though they could not dissolve in water.     

Chainlength dependence of thermodynamic properties of poly(ethylene glycol)

Investigations of ten poly(ethylene glycol) samples with molecular weights of 62 to 20 000 showed that inverse gas chromatography is a sensitive tool to determine molecular weight dependent variations of thermodynamic parameters like specific retention volume, activity coefficient, and Flory-Huggins interaction parameter. As mobile phase 27 probe molecules with various functional groups could be characterized with respect to their solubility behaviour for the oligomers and polymers due to the ability to form hydrogen bonds. By application of the factor analysis technique two factors could be extracted from the data matrix of retention values. The best fit of the corresponding simple structure was achieved with a combination of group concentrations of the terminal OH-group and the repeating ether unit of the poly(ethylene glycol)s.     

Block copolymers with poly(oxy-1,4-phenylene) and liquidcrystalline polyester segments

Block copolymers were synthesized composed of an isotropic, crystallizable poly(oxy-1,4-phenylene) block and a thermotropic liquid-crystalline (LC) polyester block. Crystalline as well as amorphous LC polyesters were used, derived from substituted poly(1,4-phenylene terephthalate). The block of poly(oxy-1,4-phenylene) was introduced via telechelic 1 . 1 was prepared with a functionality of 2 in a Cu-catalyzed reaction of 4-bromophenolate 4 with 4,4′-isopropylidenediphenol (bisphenol A). The molecular weight of the telechelic is given by the ratio 4 /bisphenol A. The increase in molecular weight during formation of the block copolymer is shown by viscosity and gel-permeation chromatography measurements. The maximum weight loss of the block copolymer as obtained by thermogravimetry is in the range of 450–500°C. Both segments in the block copolymers have a strong influence on their mutual crystallization behaviour. Short segments of poly(oxy-1,4-phenylene) suppress the crystallization of both blocks. When using longer segments of poly(oxy-1,4-phenylene) the melting endotherms of both blocks are observed, but the degree of crystallinity is lower than that of the homopolymers. The fracture behaviour of the liquid-crystalline polyester 2a is changed by modification with 20 wt.-% of poly(oxy-1,4-phenylene) and the shear-banded texture is lost.     

Preparation and characterization of ibuprofen-loaded poly(lactide-co-glycolide)/poly(ethylene glycol)-g-chitosan electrospun membranes

Ibuprofen-loaded composite membranes composed of poly(lactide-co-glycolide) (PLGA) and poly(ethylene glycol)-g-chitosan (PEG-g-CHN) were prepared by electrospinning. The electrospun membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), mechanical evaluation and contact angle measurements. Shrinkage behavior of the membrane in buffer at 37 degrees C was also evaluated. It was found that PLGA glass transition temperature (Tg) decreased with increasing PEG-g-CHN content in the composite membranes, which results in a decrease in tensile stress at break but an increase in tensile strain of the membranes. The degree of shrinkage of these composite membranes decreased from 76 to only 3% when the PEG-g-CHN content in the membranes increased from 10 to 30%. The presence of PEG-g-CHN significantly moderated the burst release rate of ibuprofen from the electrospun PLGA membranes. Moreover, ibuprofen could be conjugated to the side chains of PEG-g-CHN to prolong its release for more than two weeks. The sustained release capacity of the PLGA/PEG-g-CHN composite membranes, together with their compliant and stable mechanical properties, renders them ideal matrices for atrial fibrillation.     

Dipole moments of poly(oxytetramethylene) and poly(oxydecamethylene) chains

Dielectric constants have been determined for poly(oxytetramethylene) and poly(oxydecamethylene) chains in the thermodynamically good solvent benzene. The data for the former polymer indicate that the dipole moment ratio 〈μ²〉/(Nm²), is independent of the chain length as has been predicted for chains of such structural features. The value of this ratio for α-hydro-ω-hydroxypoly(oxydecamethylene) chains is in the same range as that obtained for poly(oxyethylene), poly(oxytetramethylene) and poly(oxyhexamethylene) and is in fair agreement with that predicted by the isomeric state theory.     

Dynamic mechanical behavior of poly(ether ether ketone)/poly(ether sulfone) block copolymers

Poly(ether ether ketone) (PEEK)/poly(ether sulfone) (PES) block copolymers were synthesized via condensation reaction between fluorine-terminated PEEK oligomers and hydroxyl-terminated PES oligomers. The dynamic mechanical behavior of a composite sample prepared by compression molding of a glass fibre cloth and the copolymer was investigated by means of a dynamic viscoelastometer. The β relaxation peak and the α′ relaxation peak were observed in the logarithmic decrement curve of the amorphous block copolymer of PEEK/PES. The glass transition temperature (β relaxation peak) is shifted to higher temperature and approaches a constant value as annealing time and degree of crystallinity increase. The glass transition temperature of the copolymer rises more slowly upon annealing with increasing PES content. The α′ relaxation peak becomes smaller upon annealing, and eventually disappears. The α′ relaxation peaks are related to the motion of molecules upon transition from the non-crystalline to the crystalline state. The α′ relaxation occurs for the copolymer with a degree of crystallinity of 0 to 3%.     

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.     

Grafting reactions and heparin adsorption of poly(amidoamine)-grafted poly(urethane amide)s.

Differently terminated poly(amidoamine) (PAA) oligomers were grafted on the surface of poly(ether urethane amide)s (PEUAm), with fumaric or maleic acid moieties. The grafting reaction was Michael-type addition of amino groups to activated double bonds in the PEUAm backbone. PAAs having primary amino, or secondary amino end-groups were directly grafted on the surface of PEUAm sheets. For vinyl-terminated chains an alpha, omega amino-polyether spacer was introduced initially, following the same addition mechanism. Ungrafted and grafted materials were characterized, besides other analytical techniques, by ATR FT-IR spectroscopy. The heparin adsorption on PEAUm films was analysed after its elution from heparinized samples, quantified by coagulation tests (aPTT), and related to the presence of the PAAs chains grafted on to the surface. Results indicate that PAA-grafted PEUAm elastomeric biomaterials, display enhanced heparin adsorption abilities.