Chemical–physical behavior of hydrogels of poly(vinyl alcohol) and poly(ethylene glycol)

New hydrogels based on polyethylene glycol (PEG) and poly(vinyl alcohol) (PVA) of different degrees of hydrolysis were synthesized. To form the network the PEG was modified at their ends with acyl chloride groups to be used as the crosslinking agent. The compositions of the hydrogels were between 50% and 90% by weight of PEG and PVA of various degrees of hydrolysis were used. It was found that the degree of hydrolysis of the PVA and the PEG content influence the equilibrium water content of the hydrogel. The process of swelling of all the hydrogels prepared followed a second-order kinetics.     

Functional gigaporous polystyrene microspheres facilitating separation of poly(ethylene glycol)–protein conjugate

A novel sulfopropyl gigaporous polystyrene (SP-GP) microsphere enhancing the separation of poly(ethylene glycol)–protein (PEGylated protein) was first presented. The SP-GP microspheres were successfully prepared by introducing sulfopropyl groups into agarose-coated gigaporous polystyrene microspheres and used as chromatography media. Compared with a commercial medium, SP-GP microspheres exhibited improved column efficiency and reduced backpressure with increasing flow velocity, which could ensure its use in high-speed chromatography. Furthermore, a higher protein recovery and purity of the PEGylated protein could be obtained, even when SP-GP was applied at a flow velocity of 1224 cm h⁻¹. Additionally, the dynamic binding capacity (DBC) of SP-GP was significantly improved, which was higher than 10 mg mL⁻¹ medium even at a flow velocity of 306 cm h⁻¹. Further investigation using a laser scanning confocal microscope (LSCM) demonstrated that the static adsorption equilibrium of the PEGylated protein on SP-GP could be completed in 5 min, whereas a much longer period (ca. 60 min) was required for the commercial medium, indicating that the mass transfer of SP-GP was much faster with the gigaporous structure. All of these results strongly support that our developed SP-GP could serve as a promising cation exchange chromatography resin for high-speed separation, especially for biomolecules of high molecular weight.     

Controlling the properties of poly(amino ester urethane)–poly(ethylene glycol)–poly(amino ester urethane) triblock copolymer pH/temperature-sensitive hydrogel

A series of triblock copolymers composed of poly(ethylene glycol) (PEG) and poly(β-amino ester urethane) (PAEU) was synthesized and characterized. Its aqueous solution can be used as a non-cytotoxic, biodegradable, and pH/temperature-sensitive hydrogel system. The copolymer solutions exhibited sol-to-gel and gel-to-sol transitions with increasing pH and temperature, respectively. The properties of this hydrogel system, such as its sol–gel transition diagram, mechanical properties, and degradation rate, can be controlled by modulating the PEG molecular weight, PAEU block length, copolymer concentration, or structure of the monomers. The presence of urethane groups and ionized tertiary amine groups in the copolymer solution at lightly acidic pH may lead to a strong interaction of the copolymer with formulated bioactive therapeutic agents, while the existence of the gel state under physiological conditions (37 °C, pH 7.4) may enable this copolymer hydrogel to be applicable as a drug/protein carrier.     

Thermal characterization of biodegradable methoxy poly(ethylene glycol)-b-poly(d,l-lactide)/methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) blend nanoparticles

Biodegradable methoxy poly(ethylene glycol)-b-poly(d,l-lactide) (MPEG-b-PDLL) and methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (MPEG-b-PCL) diblock copolymers were synthesized by ring-opening polymerization of DLL and CL monomers in bulk using stannous octoate, and MPEG as the initiating system. Surfactant-free MPEG-b-PDLL/MPEG-b-PCL blend nanoparticles were prepared by the nanoprecipitation method. The influences of block length and blend ratio on morphology, average size, and thermal properties of the blend nanoparticles were determined. The blend nanoparticles were spherical in shape. The average particle sizes slightly decreased as the MPEG-b-PCL blend ratio increased. ¹H-NMR and thermogravimetry revealed the different MPEG-b-PDLL/MPEG-b-PCL blend ratios of the nanoparticles. Differential scanning calorimetry showed that the MPEG-b-PCL crystallinity steadily decreased as the MPEG-b-PDLL blend ratio increased, suggesting miscible blending between the MPEG-b-PDLL and MPEG-b-PCL in the amorphous phase of the nanoparticle matrix.     

Self-diffusion in poly(N -vinyl pyrrolidone) – poly(ethylene glycol) systems

 We have applied the PFG NMR technique to investigate the translational mobility in the PVP-PEG system as a function of composition and temperature at the stages of PVP-PEG complex formation, its swelling, and dissolution in excess of liquid PEG. It has been found that the variations of the spin-echo attenuation with PEG content, water amount, and temperature reflect the different stages. The first two stages are characterized by a distribution of the self-diffusion coefficients of PEG involved in the network. The dissolution shows two diffusion coefficients; the fast one is attributed to PEG molecules, the slow one to the associates of PEG and PVP. The temperature dependencies can be described by an Arrhenius law with an activation energy depending on the composition of the blend. The concentration dependence of the PEG self-diffusion coefficients in the blend occurred to be independent of the molecular weight of PVP. The results are discussed in terms of the Mackie-Meares model. Received: 23 August 2000 Accepted: 19 October 2000     

Synthesis and characterization of poly(ethylene glycol) based β-cyclodextrin polymers

A series of novel water soluble β-cyclodextrin (βCD) polymers has been synthesized from functionalized poly(ethylene glycol) (PEG). The chemical composition of the polymers has been characterized by ¹H NMR and the βCD content is found to be between 48 and 33% (w/w). The molecular weight has been determined by Size Exclusion Chromatography (SEC) and depends on the ratio between βCD and PEG, varying from 2.1 × 10⁴ to 8.6 × 10⁴ g mol^?1. The physico chemical properties have been characterized by differential scanning calorimetry (DSC), viscometry and isothermal titration calorimetry (ITC). ITC shows that the polymers have association constants comparable to βCD with different guest molecules, indicating a good accessibility of the CDs.     

Enzymatic synthesis of poly(α-ethyl β-aspartate) by poly(ethylene glycol) modified poly(aspartate) hydrolase-1

We recently discovered that poly(aspartate) (PAA) hydrolase‐1 from Pedobacter sp. KP‐2 has a unique property of specifically cleaving the amide bond between β‐aspartate units in thermally synthesized PAA (tPAA). In the present study, the enzymatic synthesis of poly(α‐ethyl β‐aspartate) (β‐PAA) was performed by taking advantage of the substrate specificity of PAA hydrolase‐1. No polymerization of diethyl L ‐aspartate by native PAA hydrolase‐1 occurred because of the low dispersibility of the enzyme in organic solvent. Poly(ethylene glycol) (PEG) modification of the enzyme improved its dispersibility and enabled it to polymerize the monomer substrate. MALDI‐TOF MS analysis showed that the synthesized polymer was observed in the range of m/z = 750–2 500. This analysis also revealed that the polymer was composed of ethyl aspartate units, containing either an ethyl ester or a free carboxyl end group at its carboxyl terminus. ¹H NMR analysis demonstrated that the synthesized polymer consisted of only β‐amide linkages. Thus, the present results indicate that PAA hydrolase‐1 modified with PEG is useful for the synthesis of β‐PAA due to its unique substrate specificity and good dispersibility in organic solvent.

     

Novel crosslinked thermoresponsive hydrogels with controlled poly(ethylene glycol)—poly(propylene glycol) multiblock copolymer structure

New thermoresponsive crosslinked hydrogels with controlled multiblock copolymer structure were prepared from equimolar amounts of α,ω-diamino poly(propylene glycol)s with molecular weights (MW) 230, 400, and 2,000 g mol^?1 and diepoxy-terminated poly(ethylene glycol)s of approximate MW 1,000; 2,000; and 4,000 g mol^?1. Their thermoresponsive character was investigated on the 10–70 °C interval, while the swelling behavior was tested at 21, 37, and 50 °C. All hydrogels displayed temperature sensitivity, but a volume phase transition was noticed only in the case of poly(propylene glycol) (PPG)₂₀₀₀-containing hydrogels. The volume phase transition temperature (T _VPT ) depended on the MW of the hydrophilic poly(ethylene glycol) (PEG) chains attached to the PPG₂₀₀₀ block, as well as on the added salts. Longer PEG blocks determined a shift of T _VPT towards higher values, while the influence of the salt added was in agreement with the Hofmeister series, except for NaH₂PO₄ which determined the destruction of the hydrogel network. The equilibrium swelling degree depended on the MW of both PEG and PPG blocks, as well as on temperature. The analysis of the swelling process indicated a modification of the gel characteristics with temperature and second-order kinetics for the water penetration into the hydrogel.     

Composite poly(vinyl alcohol)–poly(sulfone) membranes crosslinked by trimesoyl chloride: Characterization and dehydration of ethylene glycol–water mixtures

Composite membranes prepared from poly(vinyl alcohol) and poly(sulfone) were crosslinked with trimesoyl chloride (TMC) solutions. The degree of crosslinking, crystallinity, surface roughness and hydrophobicity of the crosslinked PVA–PSf membranes were determined from attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), X-ray diffraction (XRD), atomic force microscopy (AFM) and contact angle measurements, respectively. Results showed a consistent trend of changes in the physicochemical properties: the degree of crosslinking, crystallinity, surface roughness, hydrophobicity and swelling degree all decrease with increasing crosslinking agent (TMC) concentration and reaction time. The crosslinked membrane performance was assessed with pervaporation dehydration of ethylene glycol solutions at a range of concentrations (30–90 wt% EG) in the feed mixtures. The total flux of permeation was found to decrease, while the selectivity to increase, with increasing TMC concentration and reaction time. The decrease in flux was most prominent at low EG concentrations in the feed mixtures. In addition, the temperature effect on the pervaporation dehydration was investigated in relation to solution–diffusion mechanisms.     

Synthesis of carbon nanofibers from poly(ethylene glycol) with controlled structure

Through fine tuning of synthesis conditions, we successfully synthesized three types of carbon nanofiber (CNF) (herring-bone carbon nanofiber, platelet carbon nanofiber, and cup-stacked carbon nanofiber) by the thermal decomposition of a mixture of poly(ethylene glycol) (PEG) and nickel chloride (NiCl₂). A series of experimental results demonstrated that the key factors for the selective synthesis of these CNFs were the (1) NiCl₂/PEG ratio, (2) drying time of the polymeric mixture, (3) state of PEG (liquid or solid) before temperature rising, and (4) temperature profile during the thermal decomposition. Changes in these conditions contributed to the formation of Ni catalyst particles from the catalyst NiCl₂ with different morphology, thereby resulting in the growth of different types of CNF or amorphous carbon products according to the catalyst particle’s shape. Also, we found that the mechanism of CNF growth in this synthesis method was fundamentally the same as that in chemical vapor deposition (CVD).     

Thermal degradation of two classes of block copolymers based on poly(lactic-glycolic acid) and poly(ϵ-caprolactone) or poly(ethylene glycol)

Thermodegradative investigations of two classes of multi-block copolymers containing poly(D,L-lactic-glycolic acid) (PLGA) and either poly(ethylene glycol) (PEG) or poly(ϵ-caprolactone) diol-terminated (PCDT) segments were performed. In particular, the influence of the type and length of the segments as well as of the molar ratio between the D,L-lactic acid (LA) and glycolic acid (GA) residues was investigated at 180°C in air by viscometry, FT-IR analysis and isothermal thermogravimetry. The thermal oxidative degradation of these materials is largely affected by the LA/GA ratio, a higher LA content generally imparting higher stability. The FT-IR analysis suggests that, depending on the composition of the PLGA segments, degradative processes are triggered which can lead to a preferential degradation of the blocks.     

Effect of block lengths on the association behavior of poly(l-lactic acid)/poly(ethylene glycol) (PLA–PEG–PLA) micelles in aqueous solution

A series of poly(l-lactic acid)/poly(ethylene glycol) triblock copolymers with a PLA–PEG–PLA architecture were synthesized by a ring-opening polymerization (ROP) process. The copolymers were characterized by ¹H NMR and GPC. The total number average molecular weights were in the range of 4,700–50,000, whereas the degrees of polymerization of the PLA and PEG blocks varied from 15 to 359 and from 68 to 136, respectively. The self-association of these copolymers in aqueous environment was studied by emission fluorescence spectroscopy of anilinonaphthalene probe and the critical association concentration (CAC) of the copolymers was measured. It was found that the micellization process of these copolymers was mainly determined by the length of the hydrophobic LA block, while the length of the hydrophilic PEG block had little effect. Furthermore, the low CAC values of the copolymers suggest that the copolymers form stable supramolecular structures in aqueous solutions.     

Thermo-physical properties of pure ethylene glycol and water–ethylene glycol mixture-based boron nitride nanofluids

Journal of Thermal Analysis and Calorimetry - Nanofluids are suspensions of solid nanoparticles in conventional heat transfer fluids, and they often exhibit improved heat transfer characteristics....     

Selective assembly of cyclodextrins on poly(ethylene oxide)–poly(propylene oxide) block copolymers

This paper presents a computational study on the formation of a molecular necklace formed by specific threading of cyclodextrins (CDs) on block copolymers. Structural as well as energetic principles for the selective complexation of - and -cyclodextrin with poly(ethylene oxide)–poly(propylene oxide) block copolymers (PEO–PPO) are elucidated considering a diblock copolymer of equimolecular composition (PEO)4–(PPO)4 as guest. A non-statistical distribution of CDs, i.e. -CDs primarily located on the PEO chain and -CDs on PPO blocks of the polymer, is based on a variety of structural features and energetic preferences considering both potential as well as solvation energies. This selectivity becomes already obvious considering 1:1 complexes between PEO and PPO monomers and the two CDs, but is increasingly evident when calculating higher order ensembles. Besides the host–guest interaction, docking between CDs themselves is an important, also non-statistical, prerequisite for the self-assembly of highly ordered tubes. The formation of intermolecular hydrogen bonds between adjacent CDs in a tubular aggregate gives an important contribution to the overall stability of the molecular necklace. The net effect, based on the preferential interaction between host and guest as well as between the host molecules themselves, results in the formation of a stable, highly ordered macromolecular, multicomponent aggregate.     

Hydrolytic and microbial degradation of multi-block polyurethanes based on poly(?-caprolactone)/poly(ethylene glycol) segments

Biodegradable amphiphilic multi-block poly(ether-ester-urethane)s were prepared by one-step bulk polycondensation of PEG and PCL macro-diols and HMDI. For biomedical or environmental applications of the proposed materials, one of the critical steps is the study of the degradation characteristics under physiological or environmental conditions. Different ratios of PEG/PCL and molecular weights of the resultant copolymers allowed for tuning their hydrophilicity, as evaluated by water uptake measurements. The swelling results were further supported by microgravimetric measurements performed by QCM-D. In vitro hydrolytic biodegradation was carried out under different conditions (i.e., in phosphate buffer solution - with and without Lipase). Total mineralization in the presence of microorganisms from a sample of river water was observed to follow different kinetics, depending upon the composition and the molecular weight of the copolymer.     

Photochemistry of nonconjugated bichromophoric systems Ⅲ. Synthesis and photoreaction of poly(ethylene glycol) biscoumarinyloxyacetates

A series of poly(ethylene glycol) biscoumarinyloxyacetates have been synthesized and their intramolecular photochemical cyclodimerizations have been studied.It was found that only syn-HT configuration products were obtained when these bisesters were directly irradiated in chloroform,and the yields of the products decreased with the increase of the chain length.This photocyclization reaction is a convenient and effective method to synthesize macrocyclic compounds.     

Microwave-Assisted Synthesis of Poly(ε-caprolactone)-block-poly(ethylene glycol) and Poly(lactide)-block-poly(ethylene glycol)

Summary: This study reported the preparation and characterization of PCL-b-mPEG (poly(ε-caprolactone)-block-poly(ethylene glycol)) and PLL-b-mPEG (poly(L-lactide)-block-poly(ethylene glycol)) diblock copolymers by microwave heating and comparison of resulted products the ones with prepared by conventional heating. Diblock copolymers were synthesized successfully by the microwave-assisted ROP in the presence of stannous octoate (SnOct₂) as catalyst under nitrogen atmosphere in different monomer ratios. Structural and functional characterization of copolymers were performed by FTIR, ¹H-NMR and DSC. Molecular weight values were determined by GPC and also calculated from ¹H-NMR. According to the results, microwave irradiation allowed to obtain polymers with very narrow size distribution in very short reaction time. Similar polymers prepared by conventional heating were also synthesized for comparison. Molecular weight and conversion of polymers were increased by irradiation time. This change was continued until a certain time point after which no more increase was observed. It was concluded that microwave irradiation is a succesful method to obtain these diblock copolymers in very short reaction time and with a similar conversion obtained by conventional method.     

Determination of the molecular weight of poly(ethylene glycol) in biological samples by reversed-phase LC–MS with in-source fragmentation

PEGylation has been widely used to improve the biopharmaceutical properties of therapeutic proteins and peptides. Previous studies have used multiple analytical techniques to determine the fate of both the therapeutic molecule and unconjugated poly(ethylene glycol) (PEG) after drug administration. A straightforward strategy utilizing liquid chromatography–mass spectrometry (LC–MS) to characterize high-molecular weight PEG in biologic matrices without a need for complex sample preparation is presented. The method is capable of determining whether high-MW PEG is cleaved in vivo to lower-molecular weight PEG species. Reversed-phase chromatographic separation is used to take advantage of the retention principles of polymeric materials whereby elution order correlates with PEG molecular weight. In-source collision-induced dissociation (CID) combined with selected reaction monitoring (SRM) or selected ion monitoring (SIM) mass spectrometry (MS) is then used to monitor characteristic PEG fragment ions in biological samples. MS provides high sensitivity and specificity for PEG and the observed retention times in reversed-phase LC enable estimation of molecular weight. This method was successfully used to characterize PEG molecular weight in mouse serum samples. No change in molecular weight was observed for 48 h after dosing.

pH-responsive star-shaped functionalized poly(ethylene glycol)-b-poly(ε-caprolactone) with amino groups

Functional star-shaped 4-arm poly(ethylene glycol)-b-poly[(ε-caprolactone-co-γ-amino-ε-caprolactone)] (4-arm PEG-b-P(CL-co-ACL) was synthesized through ring-opening polymerization. The structure of the copolymer was confirmed by ¹H NMR, Fourier transform infrared spectroscopy (FTIR), and gel permeation chromatography (GPC). To further understand the copolymers, the difference of the conversion rate between ε-caprolactone (CL) and γ-(carbamic acid benzyl ester)-ε-caprolactone (CABCL) and the detailed deprotection condition were studied. The thermal property of the copolymer was analyzed by WAXR and differential scanning calorimetry (DSC), which demonstrated that the thermal property could be well adjusted. The pH-responsive behavior of the copolymers was studied in detail by dynamic light scattering (DLS), pH titration, and pyrene fluorescence methods, which indicated that it could form micelles and exhibit pH responsibility. Moreover, the copolymer was nontoxic and had good biocompatibility according to the results by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay.     

Synthesis and characterization of aba-type block copolymer of poly(ϵ-caproplactone) with poly(ethylene glycol), by mean of activation end groups

Poly(?-caprolactone)-b-poly(ethylene glycol)-b-poly(?-caprolactone) (PCL-b-PEG-b-PCL) triblock copolymer were synthesized by mean anionic activation of the hydroxyl end groups of poly(ethylene glycol) in presence of diphenylmethylsodium. Copolymers were characterized by SEC, FT-IR and ¹H-NMR spectroscopy, TGA and DSC. Size exclusion chromatographic analysis of obtained copolymers indicated incorporation of CL monomer into PEG without formation of PCL homopolymer. Characterization by FT-IR and ¹H NMR spectroscopy of the resulting polymeric products, with respect to their structure, end-groups and composition, showed that they are best described as ester-ether-ester triblock copolymers, whose compositions can be adjusted changing the feeding molar ratio of PEG to CL. The thermal stability of triblock copolymers was less that PEG precursor, but higher that PCL homopolymer. Analysis by mean DSC showed that all copolymers were semi-crystalline and their thermal behavior depending on their composition.