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Poly(Ethylene Glycol) Chemistry: Biotechnical and Biomedical Applications

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Abstract

At first glance, the polymer known as poly(ethylene glycol) or PEG appears to be a simple molecule. It is a linear or branched, neutral polyether, available in a variety of MWs, and soluble in water and most organic solvents. Despite its apparent simplicity, $${HO - {{\left( {C{H_2}C{H_2}O} \right)}_n} - C{H_2}C{H_2}OH} \hfill \\ {poly(ethylene\,glycol)}$$ this molecule is the focus of much interest in the biotechnical and biomedical communities. Primarily this is because PEG is unusually effective at excluding other polymers from its presence when in an aqueous environment. This property translates into protein rejection, formation of two-phase systems with other polymers, nonimmunogenicity, and nonantigenicity. In addition, the polymer is nontoxic and does not harm active proteins or cells although it interacts with cell membranes. It is subject to ready chemical modification and attachment to other molecules and surfaces, and when attached to other molecules it has little effect on their chemistry but controls their solubility and increases their size. These properties, which are described in more detail below, have led to a variety of important biotechnical and biomedical applications, a summary of which is also presented below.

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... Polymer-drug conjugation (Harris, 1992;Harris and Chess, 2003;Haag and Kratz, 2006;Pelegri-O'Day et al., 2014;Hoffman, 2016;Ekladious et al., 2019) was first described in the 1954 by German chemist, Horst Jatzkewitz, who demonstrated that covalent attachment of poly (vinyl pyrrolidone) to the psychoactive compound, mescaline, could be used to prolong its circulation and duration of action ( Figure 1A) (Jatzkewitz, 1954;Jatzkewitz, 1955;Luxenhofer, 2020). Yet despite its novelty and utility, Jatzkewitz's innovation went largely unnoticed until the mid 1970s when it was revived by Ringsdorf, Kopecek, and Duncan, among others, who championed the notion that these novel macromolecules could enhance the suboptimal activity of various pharmaceuticals (Ringsdorf, 1975). ...
... PEG's remarkable hydrophilicity, flexibility, inertness, and relative biocompatibility have found the polymer numerous uses beyond modulating drug circulation or activity and today it can be found near ubiquitously in both consumer products such as detergents, cosmetics, and car wax, as well as in industrial applications including electroplating, historical artifact preservation, and molded product production (Harris, 1992;Prime and Whitesides, 1993;Harris and Chess, 2003;Li et al., 2005;Jokerst et al., 2011). PEGylating has also been used to improve stability of contrast agents for in vivo fluorescence imaging, photodynamic therapy, and sonodynamic therapy (Ding et al., 2018;Chen et al., 2021;Xu et al., 2022). ...
... Given 1) the therapeutic impact of PEG on drug immunogenicity, 2) the possible increasing prevalence of preexisting and drug-induced PEG immunity, 3) the growing public need for safe and effective mRNA vaccines, and 4) our prevailing reliance on PEG for use in clinically approved nucleic acid and polymer-drug conjugate therapies (Schoenmaker et al., 2021), it is clear that the development and clinical validation of alternatives to (or derivatives of) PEG represents not only an unmet clinical need but also one with broad public health and national strategic interest. Indeed, the need for alternatives to PEG is a common refrain among those in the field (Harris, 1992), one as old as the first polymer-drug conjugate, Adagen; however, given the wide variety of potential candidate macromolecules such as polysaccharides, polyglycerols, and glycopolymers, (reviewed in detail elsewhere (Knop et al., 2010;Pelegri-O'Day et al., 2014;Bludau et al., 2017;Ekladious et al., 2019;Xu et al., 2022)), it begs the question as to why alternatives have yet to be approved (and studied post-approval) beyond poly(styrene co-maleic acid) (1993, Japan). Concerns over PEG immunogenicity have led some pharmaceutical companies to shy-away from or drop PEGylated products from their pipelines entirely (de Vrieze, 2020), thus the prospect of biopharma advancing clinically untested polymers through lengthy and expensive clinical trials is a difficult ask in the absence of a thoughtful incentive structure. ...
... un changement de température, de force ionique ou de pH selon le composé) comme phase dispersée permet de favoriser la création des microsphères ou de billes (Millqvist-Fureby, 2014). Pour la phase continue, le polyéthylène glycol est intéressant car il possède un large volume d'exclusion envers les protéines et permet la coacervation des molécules de gélatine (Harris, 1992;Jizomoto, 1985). De plus, il est non toxique, biocompatible et permet de préserver l'activité biologique dans le cas d'encapsulation de substances actives comme des enzymes ou peptides. ...
... Comme cela a été détaillé dans le chapitre 1, paragraphe IV-3.a), le polyéthylène glycol a lui aussi la capacité d'induire une agrégation des molécules de gélatine pour donner des gouttelettes (Harris, 1992;Kong et al., 2011). Le polyéthylène glycol et la gélatine peuvent ainsi former deux phases distinctes grâce aux larges volumes d'exclusion du PEG et à l'absence sur le PEG de sites acides sur lesquels pourraient se fixer les protéines. ...
... (Bhat and Timasheff, 1992). Des concentrations plus importantes en PEG10 favorisent aussi le repliement de la protéine, permettant de former des billes de plus petit diamètre (Harris, 1992 En résumé, les paramètres choisis pour l'élaboration des billes utilisées pour la suite des travaux de cette thèse sont regroupés dans le Tableau 3-4. Ces conditions permettent la formation de billes dont le diamètre déterminé expérimentalement selon la méthode décrite au chapitre 2, paragraphe III-2.g) ...
Thesis
Ce travail de thèse a pour objectif l’élaboration de supports d’immobilisation d’enzymes bio sourcés en vue de la dégradation de micropolluants dans l’eau. Des billes de gélatine de diamètre moyen 1,9 mm ont été formées dans ce but par un procédé de goutte à goutte n’employant aucun solvant organique. La réticulation des billes par le glutaraldéhyde permet d’une part de limiter le gonflement de ce polymère dans l’eau et d’améliorer sa tenue mécanique en immersion, et d’autre part de créer des liaisons covalentes entre la gélatine et la laccase. Un plan d’expérience 2^4 a été réalisé afin d’identifier les paramètres influant sur l’efficacité du greffage.La dégradation de deux micropolluants par les billes activées a été étudiée en réacteur agité et dans un réacteur à lit fluidisé conçu pour ce projet. La tétracycline s’est montrée sensible à l’oxydation par les laccases greffées à la surface des billes. Divers paramètres ont été étudiés comme le pH de la solution, le débit de recirculation, ou l’addition d’oxygène dans le système. Le glyphosate s’est montré plus récalcitrant à l’action de la laccase seule à cause d’une structure plus complexe. L’ajout d’un médiateur d’oxydoréduction, l’ABTS, a néanmoins permis de faciliter son oxydation. La co-immobilisation du médiateur et du biocatalyseur sur les supports à base de gélatine a été étudiée, afin de limiter l’impact économique et environnemental du projet.
... : I In nt tr ro od du uc ct ti io on n 11 1.1 La thérapie génique 12 1.2 La thérapie génique anticancéreuse 13 18 Propriétés physico-chimiques 40 Utilisation chimique 41 Propriétés biologiques de biochimiques 42 Synthèse des mPEG-NH 2 44 46 Généralités 46 Structure des PEI 46 Physico-chimie des PEI 47 Capacité de transfection de l'ADN et des oligonucléotides 49 Ciblage des cellules 51 Caractères toxiques 52 Synthèse du L-PEI 53 3.1.2 Effets du mPEG-OH, et du L-PEI sur l'activité gélatinase 55 57 3 63 74 78 83 84 87 ...
... 3.3.1 Cinétique d'hydrolyse de substrat synthétique 87 3.3.2 Hydrolyse de ce substrat par les surnageants cellulaires 90 3.3.3 ...
... Les PEGs [87], sont utilisés à concentrations élevées pour précipiter des protéines, [86]. ...
Thesis
Un peptide synthétique, substrat de gélatinases A (MMP2) et B (MMP9 a été introduit par synthèses chimiques diverses entre deux polymères : une poly(éthyleneimine), (L-PEI) et un poly(éthylène glycol)5000, (mPEG5000). La conception des produits est basée sur l’inhibition de la transfection cellulaire d’ADN lié au L-PEI, par le mPEG, lorsque le peptide incorporé n’est pas clivé par ces enzymes. Un taux plus important de transfection du gène de la luciférase, transporté par ces substrats, est obtenu avec les cellules HT1080 qu’avec les cellules B16 et 3T3, alors que pas ou peu de transfection est obtenue avec les molécules-témoins. Ces résultats sont en rapport avec les activités gélatinases des surnageants de ces cellules, permettant l’élimination du mPEG. Ils laissent envisager un ciblage de gènes thérapeutiques de cellules cancéreuses avec un vecteur synthétique.
... Polyethylene glycol (PEG) is a biocompatible, water-soluble and non-ionic polymer [1]. Because of its hydrophilic and non-toxic nature, PEG has been widely used in biomedical, pharmaceutical, cosmetic and food processing applications [1,2]. PEG has also been reported to show unique steric repulsion/exclusion property in aqueous environment due to its high flexibility and mobility with water [2]. ...
... Because of its hydrophilic and non-toxic nature, PEG has been widely used in biomedical, pharmaceutical, cosmetic and food processing applications [1,2]. PEG has also been reported to show unique steric repulsion/exclusion property in aqueous environment due to its high flexibility and mobility with water [2]. This property makes PEG to be uniquely suitable for reducing protein adsorption, cell uptake, cell stimulation and cell adhesion in body environment [1][2][3]. ...
... PEG has also been reported to show unique steric repulsion/exclusion property in aqueous environment due to its high flexibility and mobility with water [2]. This property makes PEG to be uniquely suitable for reducing protein adsorption, cell uptake, cell stimulation and cell adhesion in body environment [1][2][3]. PEG and its related polymers have been commonly used as hydrogels for drug delivery, cell delivery and tissue engineering [1,[4][5][6][7]. PEG is an FDAapproved biomedical polymeric material [3]. ...
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Abstract Hydrophilic polymers are very useful in biomedical applications. In this study, biocompatible polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP) polymers end‐capped with succinimidyl groups were either modified or synthesised and attached to polyvinylchloride surfaces. The modified surfaces were evaluated with cell adhesion and bacterial adhesion. 3T3 mouse fibroblast cells and three bacteria species were used to evaluate surface adhesion activity. Results showed that the modified surface exhibited significantly reduced 3T3 cell adhesion with a 50%–69% decrease for PEG and a 64%–81% for PVP, as compared to unmodified polyvinylchloride. The modified surface also showed significantly reduced bacterial attachment with 22%–78%, 18%–76% and 20%–75% decrease for PEG and 22%–76%, 18%–76% and 20%–73% for PVP to Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, respectively, as compared to unmodified polyvinylchloride. It seems that an appropriate chain length or molecular weight (neither the longest nor the shortest chain length) determines the lowest cell and bacterial adhesion in terms of PEG. On the other hand, a mixture of polymers with different chain lengths exhibited the lowest cell and bacterial adhesion in terms of PVP.
... TA B L E 1 Hydrodynamic radii of PEG solutions obtained by viscometry (0.1 M KCl) and solution conductivity as changed by PEG addition (20% w/w); adapted from refs. [18,19] insoluble in ethyl ether, hexane, and ethylene glycol [23]. As a result, the PEGs are frequently described as amphiphilic. ...
... PEGs are commercially available in a wide range of MWs and different sizes ( Table 1). The traditionally used PEGs are polydisperse; their MW and chain length are distributed in a certain relatively low range [23]. The monodispersed PEG products with defined discrete MWs are also available. ...
... The PEGs can be used for simple chemical modification of other molecules or surfaces. These attachments do not result in any significant changes in the chemistry of the molecules reacting with the polymers; however, their solubility and dimensions can be favorably altered [23]. PEGs are approved by the FDA for internal consumption and used extensively by pharmaceutical and cosmetic industries for drug compounding, personal care products, and other applications [23,24]. ...
Article
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Neutral water-soluble poly(ethylene glycol)s (PEGs) have been extensively explored in protein nanopore research for the past several decades. The principal use of PEGs is to investigate the membrane protein ion channel physical characteristics and transport properties. In addition, protein nanopores are used to study polymer-protein interactions and polymer physicochemical properties. In this review, we focus on the biophysical studies on probing protein ion channels with PEGs, specifically on nanopore sizing by PEG partitioning. We discuss the fluctuation analysis of ion channel currents in response to the PEGs moving within their confined geometries. The advantages, limitations, and recent developments of the approach are also addressed. This article is protected by copyright. All rights reserved.
... Other example is Salumedica, which commercializes Salubria™ a PVA cryogel for cartilage replacement. -14) and is available in large size range (Harris, 1992). PEGs with molecular weight (Mw) lower than 1000 g/mol are viscous liquids, while PEGs with higher Mw are solids. ...
... It should be mentioned that in literature, PEGs can be referred as poly(ethylene oxide) (PEO). Usually, PEG refers to polymers with Mw lower than 20,000 g/mol, while PEO refers to those with Mw higher than 20,000 g/mol (Harris, 1992). ...
Thesis
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Fibrin gels are of interest in regenerative medicine, as they mimic the provisory matrix synthesized during wound healing process. However, when prepared at physiologic concentration, these gels cannot be handled, nor stocked in dry state. To face these drawbacks, they can be associated with another polymer network, in an Interpenetrating Polymer Network (IPN). This strategy was used to associate to a fibrin network, a semi-synthetic conetwork composed of bovine serum albumin (BSA) and poly(ethylene oxide) (PEO), obtained by photopolymerization of methacrylate-modified BSA and PEG. It was demonstrated through ex vivo and in in vitro experiments that these materials have numerous potential applications, as they support on their surface, the culture of numerous cell types. Moreover, it was observed that they may be used as drug carrier for drug release applications. Moreover, the technology was optimized by modifying the methacrylate functions on the precursors for acrylate functions. This modification allowed to reduce the toxicity of the process, while preserving materials performances. It was also demonstrated that these optimized materials have different degradation mechanisms, which are controllable by their initial formulation. Finally, 2 new groups of fibrin-based IPNs were developed, by associating to a fibrin network, another protein network, the silk fibroin. Perfectly manipulable IPNs were obtained, which support on their surface the culture of fibroblasts. These materials are then very promising for skin tissue engineering, and most likely other applications.
... Inter alia, research and application in drug, protein and gene delivery systems [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] self-assembled polymers [19][20][21][22][23], nanoreactors [24,25], bioimaging contrast agent carriers [26], anti-biofouling coatings [13,[27][28][29], sensors [30,31], tissue engineering [32][33][34] requires specifically designed polymers with suitable functionalities for appropriate bioconjugation and further biomedical application [35][36][37]. Among the plethora of synthetic polymers, poly(ethylene glycol) (PEG) remains the commercially available "gold standard" for biomedical application due to its high hydrophilicity combined with good solubility in organic solvents [38], low toxicity [39], and stealth behavior [40]. In addition, structural varieties such as star-PEG and a considerable diversity of end-group functionalization [38,[41][42][43] are commercially available. ...
... Among the plethora of synthetic polymers, poly(ethylene glycol) (PEG) remains the commercially available "gold standard" for biomedical application due to its high hydrophilicity combined with good solubility in organic solvents [38], low toxicity [39], and stealth behavior [40]. In addition, structural varieties such as star-PEG and a considerable diversity of end-group functionalization [38,[41][42][43] are commercially available. Despite PEG being generally regarded safe, antibodies against PEG [44][45][46][47] and some other limitations such as toxic side products [48,49], hypersensitivity [50,51], vacuolization [52][53][54] and accumulation in the body [40,54,55] were reported. ...
Article
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Here we introduce a post-polymerization modification method of an α-terminal functionalized poly-(N-methyl-glycine), also known as polysarcosine. We utilized 4-(methylthio)phenyl piperidine-4-carboxylate as an initiator for the ring-opening polymerization of N-methyl-glycine-N-carboxyanhydride followed by oxidation of the thioester group to yield an α-terminal reactive 4-(methylsulfonyl)phenyl piperidine-4-carboxylate polymer. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes and model proteins. The new initiator yielded polymers with well-defined molar mass, low dispersity and high end-group fidelity, as observed by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectroscopy. The introduced method could be of great interest for bioconjugation, but requires optimization, especially for protein conjugation. This article is protected by copyright. All rights reserved
... Í ndice general 1 Capítulo 1 ...
... Los PoliÓxidos de Etilenos (PEO) son surfactantes no iónico de gran interés científico y tecnológico por su variedad de aplicaciones, muchas de las cuales dependen de las propiedades del polímero en solución acuosa [1]. Este tipo de polímero es comúnmente usado como lubricante, dispersante, plastificante, como agente de recuperación de aceites ternarios y como reductores de fricción en el flujo de agua a través de ductos y canales [2]. ...
Technical Report
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Este es un borrador sobre el estudio del comportamiento de cadenas cortas de polióxido de etileno en agua usando dinámica mesoscópica.
... Inter alia, research and application in drug, protein and gene delivery systems [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] self-assembled polymers [19][20][21][22][23], nanoreactors [24,25], bioimaging contrast agent carriers [26], anti-biofouling coatings [13,[27][28][29], sensors [30,31], tissue engineering [32][33][34] requires specifically designed polymers with suitable functionalities for appropriate bioconjugation and further biomedical application [35][36][37]. Among the plethora of synthetic polymers, poly(ethylene glycol) (PEG) remains the commercially available "gold standard "for biomedical application due to its high hydrophilicity combined with good solubility in organic solvents [38], low toxicity [39], and stealth behavior [40]. In addition, structural varieties such as star-PEG and a considerable diversity of endgroup functionalization [38,[41][42][43] are commercially available. ...
... Among the plethora of synthetic polymers, poly(ethylene glycol) (PEG) remains the commercially available "gold standard "for biomedical application due to its high hydrophilicity combined with good solubility in organic solvents [38], low toxicity [39], and stealth behavior [40]. In addition, structural varieties such as star-PEG and a considerable diversity of endgroup functionalization [38,[41][42][43] are commercially available. Despite PEG being generally regarded safe, antibodies against PEG [44][45][46][47] and some other limitations such as toxic side products [48,49], hypersensitivity [50,51], vacuolization [52][53][54] and accumulation in the body [40,54,55] were reported. ...
Preprint
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Here we introduce a post-polymerization modification method of an α-terminal functionalized poly-(N-methyl-glycine), also known as polysarcosine. We utilized 4-(methylthio)phenyl piperidine-4-carboxylate as an initiator for the ring-opening polymerization of N-methyl-glycine-N-carboxyanhydride followed by oxidation of the thioester group to yield an α-terminal reactive 4-(methylsulfonyl)phenyl piperidine-4-carboxylate polymer. This represents an activated carboxylic acid terminus, allowing straightforward modification with nucleophiles under mild reaction conditions and provides the possibility to introduce a wide variety of nucleophiles as exemplified using small molecules, fluorescent dyes and model proteins. The new initiator yielded polymers with well-defined molar mass, low dispersity and high end-group fidelity, as observed by gel permeation chromatography (GPC), nuclear magnetic resonance (NMR) spectroscopy and matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) mass spectroscopy. The introduced method could be of great interest for bioconjugation, but requires optimization, especially for protein conjugation.
... Polyethylene oxide (PEO) is a crystalline, thermoplastic polymer with general formula of (-O-CH 2 -CH 2 -) n . Unlike many other polymer systems, PEO is commercially available in a wide range of molecular weights from tens of repeating units (in this case the polymer is called polyethylene glycol, PEG) to higher than a million [20]. PEO is colorless, odorless, stable against heat and hydrolysis, acts as inert substance to many chemical reagents and is a non-toxic polymer. ...
... PEO can also undergo chain scission during UV irradiation: C-O bonds can break resulting in a pair of free radicals. Generally, the probability of cross-linking in aqueous medium is higher, whereas in bulk chain scission predominates over cross-linking [20,36,37]. However, the competition between the two reactions greatly depends on irradiation time, photo-initiator concentration and oxygen presence. ...
Article
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In this study, modified fibrous mats of poly(ethylene oxide) (PEO) were fabricated through the versatile technique of electrospinning. Acrylic monomers were added to PEO with different composition ratios, and the mats were irradiated. The kinetics of photo-cross-linking reaction in the presence of the acrylic cross-linkers, as well as the structural, thermal and mechanical properties of the nanofibers, were studied. The morphology of the fibrous membranes before and after water treatment was monitored, and the insoluble fraction of the fibers was measured. As a result, by tuning the photo-cross-linking reaction, the control over fibers properties was feasible. The photo-cured PEO-based nanofibrous mats showed the solubility resistance needed to use them as membranes and to apply them in aqueous environments, as in water treatment processes and biomedical applications. Graphical Abstract
... PAGs were proposed as lubricants and shale stabilizers in the 1980s [3] , and several WBDF formulations containing PAGs have been patented [4][5][6] . The PAGs may play multiple roles such as drill lubrication, bit balling prevention, loss circulation control and shale hydration inhibition when be used as additives in WBDF due to their low cost, chemical and thermal stability, as well as their biodegradable, non-toxic and non-corrosive characteristics [7][8] . As shale stabilizers, they have shown a better performance in the presence of KCl [9][10] . ...
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The mechanism of the hydrophobized poly(ethylene glycol) (PEG)/K⁺ system inhibiting shale hydration was studied by laboratory experiment. The inhibition performance was evaluated through cuttings hot-rolling dispersion, bentonite inhibition and contact angle tests. The inhibition became stronger as contact angle and PEG concentration increased. A modified cuttings hot-rolling dispersion experiment suggested that these molecular systems did not act through the thermally activated mud emulsion (TAME) mechanism. The interaction of the PEG/K⁺ with clay samples was investigated through adsorption studies and by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermogravimetric analysis (TGA). The adsorption isotherms showed that the presence of K⁺ increased the PEG affinity for the clay surface. This inhibition effect was accompanied by a reduction of the bentonite hydration with PEG adsorption, evidenced by FT-IR, TGA and differential thermogravimetric (DTG) curves. XRD patterns were conclusive in showing that the presence of K⁺ ions limited the expansion of the clay interlamellar region to only one PEG layer, and the terminal hydrophobic segments of the PEG chains turned out to be determinant in enhancement of the inhibitory efficiency. The cuttings hot-rolling dispersion was carried out on water-base drilling fluid with PEG/K⁺, which proved the inhibition performance of PEG/K⁺ in oil field drilling.
... The fields, such as computer-brain interfacing with neural probes or cardiac cellular electrophysiology, rely on development of soft microelectrode arrays that match mechanical chemical and electrical properties of the individual live cells. PEG-based hydrogels are prospective soft interface electrode materials due to their biocompatibility, 58 adjustable elastic moduli and ionic conductance (see recent review 59 and references therein). Sub-micron indexing of life cells with PEGDA microelectrodes can in principle be done using aforementioned multiphoton laser printing. ...
Article
Multi-photon polymer crosslinking evolves as the core process behind high-resolution additive microfabrication with soft materials for implantable/wearable electronics, tissue engineering, micro-robotics, biosensing, drug delivery, etc. Electrons and soft X-rays, in principle, can offer even higher resolution and printing rates. However, these powerful lithographic tools are difficult to apply to vacuum incompatible liquid precursor solutions used in continuous additive fabrication. In this work, using biocompatible hydrogel as a model soft material, we demonstrate high-resolution in-liquid polymer crosslinking using scanning electron and X-ray microscopes. The approach augments the existing electron/X-rays lithography and beam induced deposition techniques with a wider class of possible chemical reactions, precursors and functionalities. We discuss focused beam crosslinking mechanism, the factors affecting the ultimate feature size and layer-by-layer printing possibilities. The potential of this technology is demonstrated on a few practically important applications such as in-liquid encapsulation of nanoparticles for plasmonic sensing and interfacing of viable cells with hydrogel electrodes.
... The micelle has a hydrophilic structure on the outer shell and a hydrophobic structure on the inner side, which together form a nano-size that protects the poorly water-soluble drug with its own outer shell and disperses the poorly water-soluble compound in water. This allows for the dissolution of poorly water-soluble compounds in an aqueous medium [10,11]. In addition, polymeric micelles have the advantages of low critical micelle concentration, narrow particle size distribution, and low dissociation rate [12], as well as high drug filling amount [13,14]. ...
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The aim of this study was to evaluate the characterized hydration method to prepare nanoparticles using Soluplus, a block copolymer with amphipathic properties, and distearoyl phosphatidyl ethanolamine (DSPE)-PEG2000 owing to particle size distribution, zeta potential, particle stability, and transmission electron microscopy (TEM) observed and 31P-NMR spectra. The results showed that, in a suspension of DSPE-PEG2000 and Soluplus at a ratio of 1/1, the prepared microparticles were stable for five days in the dark and at 25 °C. It was also confirmed that the 1/1 suspension of DSPE-PEG2000/Soluplus was stable for five days under the same conditions with the magnesium chloride solution. TEM measurements confirmed the presence of micelle-like particles of 50 to 150 nm in the 1/1 ratio mix of DSPE-PEG2000/Soluplus. 31P-NMR spectral data confirmed that DPSE-PEG2000/Soluplus at mixing ratio of 1/1 has a strong intermolecular with the phosphate group, indicated by the fact that the peak shift and the full width at half maximum were the largest compared with DSPE-PEG2000 with the intermolecular interaction. On the basis of the findings of this study, we conclude that microparticles can be formed using DSPE-PEG2000 and Soluplus via the hydration method, and that the optimum weight ratio of DSPE-PEG2000 to Soluplus is 1/1.
... PEG is protein repellent, but perfectly biocompatible. (Jeon et al., 1991;Harris, 1992) Using a photomask and deep UV radiation allows tailored oxidation of predefined areas of the SAM, which then can be incubated with a variety of proteins, for example extracellular matrix proteins like fibronectin. The amino groups of the proteins react with the carboxy group of the oxidized pattern and form a stable peptide bond. ...
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We developed a reproducible micropatterning method to manipulate and normalize cell shape and cell-cell separation on gold. We used methoxy polyethylene glycol thiol (PEG-SH) to create a self-assembled monolayer that can be oxidized at desired shapes through a photomask with deep UV light. The oxidized PEG can be coated with extracellular matrix proteins and seeded with cells adopting the pre-defined shape. The developed and analyzed surfaces can be used in a wide range of biophysical applications.
... Non-covalent physical adsorption is desirable for some applications such as certain drug delivery systems (Richey et al. 2000) and regenerable antimicrobial textiles (Kim and Sun 2001;Sun et al. 2001). The covalent immobilizations offer some other advantages by providing the durability of active/bioactive agents, the extended half-life for biomolecules and preventing their quick metabolism (Alferiev et al. 2006;Harris 1992), as well as preventing the migration of bioactive agents to food from the active food packaging films. Grafting of polyfunctional and anchoring compounds via a spacer molecule onto the surface of the solid substrate leads to an increase in the number of available active/bioactive agents per unit area and improves the efficiency of active/bioactive agents by reducing steric restrictions. ...
Article
The access to clean water is a critical issue in the context of climate change and worldwide pollution, calling for advanced methods of purification. Recent advances in materials science, nanoscience, and analytical chemistry have led to the design of novel nanoadsorbents having a unique properties, structure, and adsorption performances. In particular, research has focused on all-inclusive adsorbents which can remove different contaminants simultaneously. Here, we review the adsorption dynamics of doped, ionic liquid-enhanced, bio-based, and chemically functionalized materials. We examine their characteristics, underlying principles of adsorption, and their potential limitations in adsorbing various metal ions and xenobiotics. We found that chemical functionalization with specific organic moieties is a preferred approach for enhancing the adsorption capacities and selectivity of raw materials. Moreover, doping can also modulate the morphology, electronic structure, and surface chemistry for higher performance. Ionic liquids are promising solvents for the synthesis of stable adsorbents, owing to ionic liquid ability to pull other molecules through hydrogen bonds or electrostatic forces.
... In recent years, Polyethylene Glycol (PEG) are used widespread in structural biology, medicine and biochemistry also in the chemical industries as well as pharmaceutical (Knowles et al., 2015). PEGs are the hydrophilic polymers and including a repeating unit of -(O-CH2 -CH2) and are water-soluble, non-toxic and non-immunogenic polymer (Harris, 2013;Gianfranco Pasut, 2014;G. Pasut et al., 2016). ...
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There is a growing recognition of the importance of cloud computing for large-scale and data-intensive applications. The distinguishing features of cloud computing and their relationship to other distributed computing paradigms are described, as are the strengths and weaknesses of the approach. We review the use made to date of cloud computing for molecular modelling projects and the availability of front ends for molecular modelling applications. Although the use of cloud computing technologies for molecular modelling is still in its infancy, we demonstrate its potential by presenting several case studies. Rapid growth can be expected as more applications become available and costs continue to fall; cloud computing can make a major contribution not just in terms of the availability of on-demand computing power, but could also spur innovation in the development of novel approaches that utilize that capacity in more effective ways.
... While resistive pulse sensing was initially developed to count particles at the microscale [3], the exploitation of nanoscale pores, either biological [4,5], or solid-state [6,7] now allows for such varied applications as sub-Angstrom particle sizing [8], DNA sequencing [9], or digital data storage [10]. The technique has seen widespread use for studies of polymer transport, and poly-ethylene glycol (PEG) [11] in particular has frequently been used as a model polymer for resistive pulse sensing with biological pores [4,12,13]. These studies have provided great insight both into the transport properties of the polymer and into details of the pore itself. ...
Preprint
The modification of surface properties by polymer adsorption is a widely used technique to tune interactions in molecular experiments, such as resistive pulse sensing with nanopores. Here, we investigate how variation of the ionic current noise through glass nanopores reflects the passive adsorption of short, neutral polymers to the pore surface. We find that the power spectral density of the noise shows a characteristic change upon adsorption of polymer, however the magnitude of this increase is strongly dependent on both polymer length and salt concentration. In particular, for short polymers at low salt concentrations no change in noise is observed, despite verification of comparable adsorption in these systems using quartz crystal microbalance with dissipation monitoring measurements. We propose that the characteristic noise is generated by small current changes associated with the movement of polymers on and off the nanopore surface and perform simple simulations to assess the feasibility of this model. Excellent agreement is obtained with experimental data using physically motivated parameters for the adsorption strength and range, supporting our molecular interpretation of the observed noise signatures in our data. This highlights the value of analysing system fluctuations as a method of elucidating molecular processes, and paves the way to using noise spectral analysis for in situ characterisation of functionalised nanopores.
... A little background of the most well-known antifouling polymer from a wide application perspective: water soluble and low toxicity poly(ethylene glycol) (PEG), can be an example to begin with. Extensive research and development have been done for biomedical applications [26,27] and still moving on [28,29]. Their high protein resistance [30] is due to the strong coordination of water molecules along the chain, and steric repulsion from the long chains [31,32]. ...
... It can present a linear or branched structure with variable molecular weights, and its functionalization with other moieties is relatively easy to perform. 173 PEG, in its native form, does not have the capacity to form hydrogels. Typically, its hydroxyl terminal groups are modified with different moieties to allow the formation of a cross-linked structure. ...
Article
Full-text available
The lack of in vitro tissue and organ models capable of mimicking human physiology severely hinders the development and clinical translation of therapies and drugs with higher in vivo efficacy. Bioprinting allow us to fill this gap and generate 3D tissue analogues with complex functional and structural organization through the precise spatial positioning of multiple materials and cells. In this review, we report the latest developments in terms of bioprinting technologies for the manufacturing of cellular constructs with particular emphasis on material extrusion, jetting, and vat photopolymerization. We then describe the different base polymers employed in the formulation of bioinks for bioprinting and examine the strategies used to tailor their properties according to both processability and tissue maturation requirements. By relating function to organization in human development, we examine the potential of pluripotent stem cells in the context of bioprinting toward a new generation of tissue models for personalized medicine. We also highlight the most relevant attempts to engineer artificial models for the study of human organogenesis, disease, and drug screening. Finally, we discuss the most pressing challenges, opportunities, and future prospects in the field of bioprinting for tissue engineering (TE) and regenerative medicine (RM).
... These materials are designed to keep bacteria in a planktonic (swimming) state [43][44][45] and thus more susceptible to antibiotics and the host immune system 10 . Non-fouling, 'bio-passive' polymer brush surfaces, such as hydrophilic polyethylene glycol (PEG) are effective, but tend to fail after a period of days [46][47] . Slippery liquid infused porous surfaces (SLIPS) show highly-effective, long term anti-fouling properties but clinical performance is still unclear 48 . ...
... Non-covalent physical adsorption is desirable for some applications such as certain drug delivery systems (Richey et al. 2000) and regenerable antimicrobial textiles (Kim and Sun 2001;Sun et al. 2001). The covalent immobilizations offer some other advantages by providing the durability of active/bioactive agents, the extended half-life for biomolecules and preventing their quick metabolism (Alferiev et al. 2006;Harris 1992), as well as preventing the migration of bioactive agents to food from the active food packaging films. Grafting of polyfunctional and anchoring compounds via a spacer molecule onto the surface of the solid substrate leads to an increase in the number of available active/bioactive agents per unit area and improves the efficiency of active/bioactive agents by reducing steric restrictions. ...
Article
The inert nature of most commercial polymers and nanomaterials results in limitations of applications in various industrial fields. This can be solved by surface modifications to improve physicochemical and biological properties, such as adhesion, printability, wetting and biocompatibility. Polymer functionalization allows to graft specific moieties and conjugate molecules that improve material performances. In the last decades, several approaches have been designed in the industry and academia to graft functional groups on surfaces. Here, we review surface decoration of polymers and nanomaterials, with focus on major industrial applications in the medical field, textile industry, water treatment and food packaging. We discuss the advantages and challenges of polymer functionalization. More knowledge is needed on the biology behind cell-polymer interactions, nanosafety and manufacturing at the industrial scale.
... These nonbranched PEG ligands have large exclusion volumes due to their high conformational entropy, and high resistance to biomolecules adsorption via steric repulsion. [59][60][61] Moreover, PEG modification is considered to be the best biocompatible material to mitigate QDs-induced adverse effects. [62][63][64] It forms a fencelike structure on the QD surface, which can effectively prevent the chemical degradation of QDs and the release of metal ions to the intracellular environment. ...
Article
The use of synthetic nanomaterials as contrast agents, sensors, and drug delivery vehicles in biological research primarily requires effective approaches for intracellular delivery. Recently, the well-accepted microelectrophoresis technique has been reported to exhibit the ability to deliver nanomaterials, quantum dots (QDs) as an example, into live cells, but information about cell viability and intracellular fate of delivered nanomaterials is yet to be provided. Here we show that cell viability following microelectrophoresis of QDs is strongly correlated with the amount of delivered QDs, which can be finely controlled by tuning the ejection duration to maintain long-term cell survival. We reveal that microelectrophoretic delivered QDs distribute homogeneously and present pure Brownian diffusion inside the cytoplasm without endosomal entrapment, having great potential for the study of dynamic intracellular events. We validate that microelectrophoresis is a powerful technique for the effective intracellular delivery of QDs and potentially various functional nanomaterials in biological research.
... PEG molecules are generally available and have a chemical formula given by R-O-(CH 2 -CH 2 -O) n -OH, where R is the alkyl group and n is the number of repeat units of oxyethylene. These surfactants are of the important class of nonionic surfactants and have been widely used in household and cleaning products, pharmaceutical processes, food industries, lubricating agents and biotechnology applications [4][5][6]. ...
Article
Full-text available
The isothermal vapor–liquid equilibrium (VLE) data for a binary system of 4-nonyl phenol diethoxylate with sec-butanol at (333.0 to 425.0) K have been measured by using a static-type apparatus. The system pressures at a given feed composition were measured to generate the P–T–x data and are further compared to the pressure values calculated using the Antoine equation. Two thermodynamic models, the UNIQUAC and the NRTL models, were selected to correlate the VLE data at various temperatures. The analysis showed that the experimental data agree well with these activity coefficient models. Finally, the solvent activities were estimated, and the values are consistent with the values calculated from the phase equilibrium data.
... Until now, various materials able to minimize the fouling on surfaces have been identified [14]. They can be classified according to their chemical composition and include poly(ethylene glycol)/oligo(ethylene glycol)-(PEG/OEG)-based materials [15], zwitterionic compounds [16], and polysaccharide-based materials [17]. ...
Article
Surface plasmon resonance (SPR) has been widely used to detect a variety of biomolecular systems, but only a small fraction of applications report on the analysis of patients’ samples. A critical barrier to the full implementation of SPR technology in molecular diagnostics currently exists for its potential application to analyze blood plasma or serum samples. Such capability is mostly hindered by the non-specific adsorption of interfering species present in the biological sample at the functional interface of the biosensor, often referred to as fouling. Suitable polymeric layers having a thickness ranging from 15 and about 70 nm are usually deposited on the active surface of biosensors to introduce antifouling properties. A similar approach is not fully adequate for SPR detection where the exponential decay of the evanescent plasmonic field limits the thickness of the layer beyond the SPR metallic sensor surface for which a sensitive detection can be obtained. Here, a triethylene glycol (PEG(3))-pentrimer carboxybetaine system is proposed to fabricate a new surface coating bearing excellent antifouling properties with a thickness of less than 2 nm, thus compatible with sensitive SPR detection. The high variability of experimental conditions described in the literature for the quantitative assessment of the antifouling performances of surface layers moved us to compare the superior antifouling capacity of the new pentrimeric system with that of 4-aminophenylphosphorylcholine, PEG-carboxybetaine and sulfobetaine-modified surface layers, respectively, using undiluted and diluted pooled human plasma samples. The use of the new coating for the immunologic SPRI biosensing of human arginase 1 in plasma is also presented.
... Introduction Polyethylene glycol (PEG) is commonly used as bio-compatible additive in bulk and on surfaces 1 . In the last decade, PEG and its monomer have been widely used as cryoprotectants of human Langmuir 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 3 embryonic stem cells (hES) cryopreservation, for example. ...
... We expect that the wild silkworm sericin could be a new candidate polymer in biomedical application. Bioactive molecules can be attached to sericin by covalent bonding in order to form the bioconjugate [4]. Sericin nanoparticles will be prepared by the attachment of polyethylene glycol (PEG) [5]. ...
Chapter
Abstract Silk sericin is the gum-like protein surrounding the fibroin in silk fibers, and generally it is removed during the fiber processing to produce fabrics. Like other silk proteins, the silk of tasar silkworms is also composed of sericin and fibroin. In this study tasar silk sericin was extracted and was confirmed to be a 70 KDa protein by SDS PAGE. The use of sericin in the field of biomedical applications has increased their use for various purposes, the extracted silk sericin was pegylated with activated PEG (MW 5000) and the conjugated product was characterized by FT-IR, 1H NMR, CD, DSC, XRD, and AF TEM and self-assembled nanoparticles were prepared.
Article
Selective ring-opening polymerization of ethylene/propylene oxide from hydroxyl-functionalized carboxylic esters is achieved by use of metal-free Lewis pair catalysts. Subsequently, quantitative in situ hydrolysis is conducted to afford well-defined α-carboxyl-ω-hydroxyl polyethers which are highly valuable for bioconjugation but usually synthesized by much more tedious and costly routes.
Chapter
Kap. 3 Band 1 ist, neben Kap. 1 Band 2, das umfangreichste Kapitel dieser 3 Bände. Es beginnt mit dem chemischen, gefolgt vom physikalischen Aufbau der Kunststoffe. Die Bindungsarten leiten das Kapitel ein. Der Zusammenhang zwischen Bindekräften und der mechanischen Festigkeit von Polyethylen schließt die Einführung ab. Die chemische Struktur von Kunststoffen wird ingenieurmäßig erläutert bis hin zum Einbau von Fremdatomen (Copolymerisation) und innere/äußere Weichmachung. Die physikalischen Ordnungszustände (amorph, teilkristallin) sowie die anwendungstechnischen Auswirkungen (Schwindung, Dichte) werden beschrieben. Vernetzte Zustände schließen an. Abschn. 3.2 befasst sich mit der Charakterisierung von Zustandsbereichen in Kunststoffen. Es folgen die Abschn. 3.3 „Mechanische Eigenschaften“, 3.4 „Weitere physikalische Eigenschaften“ und 3.5 „Chemische Eigenschaften“. Abschn. 3.6 dürfte für den Leser wertvoll sein, weil hier Kurzcharakterisierungen von 33 Polymeren abgedruckt sind. Abschn. 3.7 behandelt Zusatzstoffe für Kunststoffe. Abschn. 3.9 behandelt die thermoplastischen Elastomere TPE), gefolgt von den Elastomeren in Abschn. 3.10. Abschn. 3.11 widmet sich den Polysiloxanen. Polymere und Faserverbunde aus natürlichen und synthetischen Rohstoffen (Abschn. 3.15) sowie Duroplaste (Abschn. 3.13) schließen Kap. 3 ab. Kap. 3 wurde umfangreich überarbeitet.
Thesis
The work described in this thesis was carried out as part of a project to explore the use of solid polymer electrolytes as pH electrodes, the properties of which would be superior to those of the fragile glass membranes traditionally used. To this end, potentiometry was used to study ion transport in membranes which were composites of poly(vinyl chloride) and poly(ethylene oxide). The idea was that the hydrophilic polymer (PEO) would interact with water molecules and ionic species, and the hydrophobic polymer (PVC) would serve as an inert matrix, intimately tangled with the hydrophilic polymer to prevent its diffusion into the aqueous solution phase. It was shown that membranes prepared by co-casting polymers from solution were indeed stable in water and that the properties could be changed by change in fabrication procedure which changed the microstructure. This thesis describes the development of the membrane preparation procedure from initially pure PEO gels to processed pure PEO membranes then co-cast composite PEO and PVC membranes and finally rotary evaporated PEO-PVC membranes. The effect of the preparation procedure on the potential difference response of these membranes was investigated to correlate any structural changes to the membrane electrochemical behaviour. Membranes prepared by the various procedures were tested with thermal analysis, FTIR and polarised light optical spectroscopy to observe any trends in physical characteristics associated with structural changes. The electrical properties of these membranes were correlated with the microscopic and macroscopic membrane structure and chemical composition. It is postulated that the membranes are a nano-scale composite structure comprising interpenetrating networks of hydrophobic and hydrophilic regions of size determined by the preparation procedure. The size of these regions determine the transport properties of ions moving through the membrane. It is proposed that the dominant effect on permselectivty in the membranes studied here is a modification of the interaction between ions and water within the membrane channels formed by a hydrated hydrophilic polymer.
Article
Surface‐induced thrombosis is problematic in blood‐contacting devices composed of silicones or polyurethanes (PUs). Poly(ethylene oxide)‐silane amphiphiles (PEO‐SA) are previously shown effective as surface modifying additives (SMAs) in silicones for enhanced thromboresistance. This study investigates PEO‐SAs as SMAs in a PU at various concentrations: 5, 10, 25, 50, and 100 µmol g⁻¹ PU. PEO‐SA modified PUs are evaluated for their mechanical properties, water‐driven surface restructuring, and adhesion resistance against a human fibrinogen (HF) solution as well as whole human blood. Stability is assessed by monitoring hydrophilicity, water uptake, and mass loss following air‐ or aqueous‐conditioning. PEO‐SA modified PUs do not demonstrate plasticization, as evidenced by minimal changes in glass transition temperature, modulus, tensile strength, and percent strain at break. These also show a concentration‐dependent increase in hydrophilicity that is sustained following air‐ and aqueous‐conditioning for concentrations ≥25 µmol g⁻¹. Additionally, water uptake and mass loss are minimal at all concentrations. Although protein resistance is not enhanced versus an HF solution, PEO‐SA modified PUs have significantly reduced protein adsorption and platelet adhesion from human blood at concentrations ≥10 µmol g⁻¹. Overall, this study demonstrates the versatility of PEO‐SAs as SMAs in PU, which leads to enhanced and sustained hydrophilicity as well as thromboresistance.
Book
Polymere in technischen Produkten können unter ganzheitlicher Betrachtung nachhaltig und sicher eingesetzt werden. Für Werkstoff, Komponenten und Produktsysteme gibt dieses Werk nachhaltige Antworten auf die wichtigen technischen, wirtschaftlichen, ökologischen und sozial relevanten komplexen Fragestellungen. Der Inhalt wurde gegenüber der Vorauflage sorgfältig bearbeitet und erheblich erweitert. Die Gliederung des Werks umfasst auch die Gestaltung von Kunststoffbauteilen, die Oberflächentechnologien für Kunststoffbauteile und die Prüfung von Kunststoffen und Bauteilen. In den Ausführungen gibt es umfangreiche Informationen, Übersichten und Ergänzungen zum Extrudieren, Blasformen, Kalandrieren, Polyurethanschäumen, zur Mikrowellentechnologie, zu additiven Verfahren, über Molded Interconnected Devices, Plasmatechnologie, Trocknungsverfahren, zum Gestalten, Fügen und Verbinden, Berechnungsansätze und Simulation, über Bauteilkosten, sowie Prüfungen an Thermoplasten/Duroplasten/Elastomeren und zur Produktqualifikation. Ausgewählte Technologien werden zusammengefasst dargestellt. Band 2 des dreibändigen Werkes behandelt die Verarbeitung von Polymeren, Oberflächentechnologien sowie die Entwicklung und Gestaltung von Bauteilen.
Article
Millimeter‐size beads of gelatin are manufactured by dripping process to give enzyme supports qualified for micropollutants biodegradation in alternative wastewater treatment. The bead diameter is dependent on the tip diameter, the gelatin solution viscosity and the swelling of polymer chains in the collecting bath. Chemical crosslinking was performed with glutaraldehyde using optimal concentration to give mechanical and thermal properties suitable for application in stirred reactor in aqueous medium. Laccases from Trametes versicolor are grafted on the gelatin beads with glutaraldehyde. Sixty percentage of the initial enzymatic activity, evaluated by the oxidation of 2′‐Azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid)diammonium salt (ABTS) is maintained after 10 successive cycles of reaction. Thermal stability at 60°C of immobilized biocatalysts is improved when compared to free enzymes (45% vs 10% of relative activity after 6 h of incubation). The simplicity of the procedure to form gelatin beads and their properties make them promising bio‐based and biodegradable support for enzyme immobilization.
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Electrospinning produces nanofibrous scaffolds with potential for tissue engineering and wound repair. Spinning parameters control scaffold morphology and properties. BioPEGylation of polyhydroxybutyrate (PHB) introduces terminal hydrophilic groups into the hydrophobic chain, making this natural−synthetic hybrid copolymer more susceptible to humidity. Varying the humidity from 10 to 50% RH during electrospinning had a relatively little effect on polyhydroxybutyrate (PHB) average fiber and pore diameters, which remained around 3.0 and 8.7 μm, respectively. In contrast, fiber and pore diameters for electrospun bioPEGylated PHB scaffolds varied significantly with humidity, peaking at 30% RH (5.5 and 14.1 μm, respectively). While scaffolds showed little change, hydrophobicity decreased linearly with humidity during electrospinning. Compared to solvent-cast films, electrospun scaffolds showed significantly greater average cell spread. A 108% increase for olfactory ensheathing cells (OECs) cultivated on bioPEGylated PHB scaffolds was proportionally greater than their counterparts on electrospun PHB scaffolds, (70%). OECS grown on BioPEGylated PHB scaffolds were over twice the size, 260 ± 20 μm diameter, than those on PHB electrospun scaffolds, 110 ± 18 μm diameter. Electrospun scaffolds also promoted cell health compared to their solvent-cast counterparts, with increases in the mitochondrial activity of 165 ± 13 and 196 ± 13% for PHB and bioPEGylated PHB, respectively. OECS cultivated on electrospun scaffolds of bioPEGylated PHB had significantly better membrane integrities compared to their counterparts on solvent-cast films, 47 ± 5% reducing to 17 ± 6%. The combination of bioPEGylation and humidity during electrospinning permitted significant controllable changes to scaffold morphology and properties. These changes resulted in the significantly greater promotion of cell growth on electrospun bioPEGylated PHB scaffolds compared to their solvent-cast counterparts and electrospun PHB.
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The mechanism of separation methods, e.g. liquid chromatography, is realized through rapid multiple adsorption-desorption steps leading to the dynamic equilibrium state in a mixture of molecules with different partition coefficients. Sorting of colloidal particles, including protein complexes, cells, and viruses, is limited due to a high energy barrier, up to millions kT , required to detach particles from the interface, which is in dramatic contrast to a few kT for small molecules. Such a strong interaction renders particle adsorption quasi-irreversible. The dynamic adsorption-desorption equilibrium is approached very slowly, if ever attainable. This limitation is alleviated with a local oscillating repulsive mechanical force generated at the microstructured stimuli-responsive polymer interface to switch between adsorption and mechanical-force-facilitated desorption of the particles. Such a dynamic regime enables the separation of colloidal mixtures based on the particle-polymer interface affinity, and it could find use in research, diagnostics, and industrial-scale label-free sorting of highly asymmetric mixtures of colloids and cells.
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Tissue engineering is a multidisciplinary field that focuses on creating functional tissue through the combination of biomimetic scaffolds, a cell source, and biochemical/physiochemical cues. Stem cells are often used as the cell source due to their multipotent properties and autologous sourcing; however, the combination of physical and chemical cues that regulate their behavior creates challenges in reproducibly directing them to a specific fate. Hydrogel biomaterials are widely explored as tissue scaffolds due to their innate biomimetic properties and tailorability. For these constructs to be successful, properties such as surface chemistry and spatial configuration, stiffness, and degradability of the biomaterial used for the scaffold framework should be analogous to the natural environment of the tissue they are repairing/replacing. This is imperative, as cues from the surrounding extracellular matrix (ECM) influence stem cell behavior and direct cell differentiation to a specific lineage. Hydrogels offer great promise as tools to control stem cell fate, as researchers can modulate the degradation rates, mechanical properties, swelling behavior, and chemical properties of the biomaterial scaffold to mimic the instructive cues of the native ECM. Discussion of the advantages and challenges of utilizing hydrogel biomaterials as the basis of tissue scaffolds is reviewed herein, as well as specific examples of hydrogels in tissue engineering and advances in hydrogel research to achieve desired cell phenotypes.
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The metal oxide nanoparticles (NPs), zinc oxide (ZnO) and nickel oxide (NiO) were synthesized using Sterculia foetida (S.foetida) leaf extract by solution combustion method. The Poly(glutaric acid-co-ethylene glycol-co-acrylic acid)(GEA) hydrogel was prepared using three different monomers such as glutaric acid (G), ethylene glycol (E) and acrylic acid (A). The zinc oxide (ZnO) and nickel oxide (NiO) nanoparticles were introduced into GEA hydrogel and the polymer nanocomposites GEA-ZnO and GEA-NiO were obtained. The UV-visible spectroscopy (UV) peak observed at 275 nm and 360 nm for GEA-ZnO and GEA-NiO polymer nanocomposites. The Fourier Transform Infrared (FT-IR) spectral data obtained at 414cm⁻¹ confirmed the presence of nanoparticles in the hydrogel. The size of the nanoparticles were confirmed through Scanning Electron Microscopy (SEM) and Transmission Electron Microscope (TEM) analysis. The size of the zinc oxide nanoparticles (ZnO NPs) introduced in GEA-ZnO polymer nanocomposite was 30 to 35 nm and the size of nickel oxide nanoparticles (NiO NPs) introduced in GEA-NiO nanocomposite was 27 to 33 nm. The percentage of zinc oxide (ZnO) and nickel oxide (NiO) were reported in Energy Dispersive X-ray Analysis (EDAX) spectrum.Where the percentage of zinc (Zn) is 2.22% and nickel (Ni) is 2.7%.The thermal stability of the nanoparticles in the hydrogel was assessed by Thermo gravimetric analysis (TGA). Beyond 450οC there was no change in the Thermo Gravimetric Analysis (TGA) peak of GEA-NiO polymer nanocomposite and found with nil weight loss. The antibacterial activity was performed using Staphylococcus aureus (s.aureus)and Bacillus subtilis (B.subtilis) gram positive bacterial strains and Escherchia coli (E.coli) and Klebsiella pneumoniae (K.pneumoniae) gram negative bacterial strains. The gram positive bacteria showed highest antibacterial activity than gram negative bacteria at highest concentration 100 μg/ml towards polymer nanocomposites.
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We have prepared a series of ampholytic polymer films, using a self-initiated photografting and photopolymerization (SI-PGP) method to sequentially polymerize first anionic (deuterated methacrylic acid (dMAA)) and thereafter cationic (2-aminoethyl methacrylate (AEMA)) monomers to investigate the SI-PGP grafting process. Dry films were investigated by ellipsometry, X-ray, and neutron reflectometry, and their swelling was followed over a pH range from 4.5 to 10.5 with spectroscopic ellipsometry. The deuterated monomer allows us to separate the distributions of the two components by neutron reflectometry. Growth of both polymers proceeds via grafting of solution-polymerized fragments to the surface, and also the second layer is primarily grafted to the substrate and not as a continuation of the existing chains. The polymer films are stratified, with one layer of near 1:1 composition and the other layer enriched in one component and located either above or below the former layer. The ellipsometry results show swelling transitions at low and high pH but with no systematic variation in the pH values where these transitions occur. The results suggest that grafting density in SI-PGP-prepared homopolymers could be increased via repeated polymerization steps, but that this process does not necessarily increase the average chain length.
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New squalene receptors bearing open-chain polyether ligands (SQ-diEG, SQ-triEG, SQ-tetraEG) were synthesised. The stoichiometries and association constants (Ka) for the interactions between these squalene receptors and representative alkaline earth metal ions (Mg²⁺, Ca²⁺, and Ba²⁺) were determined in solution. Fluorescence spectral studies revealed that the squalene receptors self-associate with critical vesicle concentrations at 25 °C of 2.2 × 10⁻⁵ M for SQ-diEG, 2.3 × 10⁻⁵ M for SQ-triEG, and 2.5 × 10⁻⁵ M for SQ-tetraEG. The self-assembly behaviour was probed using laser diffraction particle size-based analyses and scanning electron microscopy. A decrease in the SQ-tetraEG vesicle size was readily induced by the addition of alkaline earth metal ions, confirmed by cryogenic transmission electron microscopy.
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The mechanism of separation methods, e.g. liquid chromatography, is realized through rapid multiple adsorption-desorption steps leading to the dynamic equilibrium state in a mixture of molecules with different partition coefficients. Sorting of colloidal particles, including protein complexes, cells, and viruses, is limited due to a high energy barrier, up to millions kT , required to detach particles from the interface, which is in dramatic contrast to a few kT for small molecules. Such a strong interaction renders particle adsorption quasi-irreversible. The dynamic adsorption-desorption equilibrium is approached very slowly, if ever attainable. This limitation is alleviated with a local oscillating repulsive mechanical force generated at the microstructured stimuli-responsive polymer interface to switch between adsorption and mechanical-force-facilitated desorption of the particles. Such a dynamic regime enables the separation of colloidal mixtures based on the particle-polymer interface affinity, and it could find use in research, diagnostics, and industrial-scale label-free sorting of highly asymmetric mixtures of colloids and cells.
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Self-regulated “smart” insulin administration system that mimic pancreatic endocrine function would be highly desirable for diabetes management. Here, a glucose-responsive continuous insulin delivery system is developed, where novel polyhedral oligosilsesquioxane (POSS) modified with 3‐aminophenylboronic acid (APBA) were used to encapsulate insulin (insulin entrapment efficiency: 73.2%) to prepare a fast response, high stability, good distribution, and excellent biocompatible system. Due to the strong hydrophobicity of POSS, the POSS moiety is located at the core in aqueous solution and combines with the boronic group of APBA and the diol generated in PEG-insulin to form a nanomicelle structure, that is, nanoparticles naturally. Micelles self‐assembled from these molecules possess glucose‐responsiveness at varying glucose concentrations. The interaction of the PBA and diol containing insulin via boronate ester bond and its interchange with glucose was investigated by FT-IR, 1H NMR and XPS. Furthermore, the successful glucose-triggered release of insulin from the POSS-APBA micelles was investigated at neutral pH. A linear graph was plotted with the measured released insulin vs glucose concentrations, with a linear correlation coefficient (R2) value close to 1. Circular dichroism (CD) spectroscopy analysis was performed to measure insulin activity by comparing secondary structures of insulin, PEG-Insulin, and POSS-APBA@insulin. When confirming intracellular apoptosis signaling, cleaved caspase 3 and caspase 9 were not increased by 640 μg/ml POSS-APBA and POSS-APBA@insulin in HeLa, HDF and HUVE cells. Application in the biomedical field for controlled delivery of insulin appear to be promising.
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Development of the biointerface for high performance immuno-sensing methods is one of the current research topics in analytical chemistry and biochemistry. We developed histidine-tagged protein A (His6-protein A)/poly(ethylene glycol) (PEG) co-immobilized gold surface as a new class of immuno-sensor chip, where both protein A and PEG are directly immobilized on the surface by the histidine-tag and the thiol group, respectively. In this study, the resulting surface was applied to sandwich assay for specific protein detection based on surface plasmon resonance measurements. Despite the similar content of immobilized antibodies, the amount of secondary antibody on His6-protein A/PEG surface was about eight times higher than that of physically adsorbed antibody/PEG surface. In addition, nonspecific protein absorption was extremely suppressed on His6-protein A/PEG surface, compared with Ni2+ -nitrilotriacetic acid (NTA) surface, which was generally used for the immobilization of histidine-tagged proteins. These results clearly indicate that effective orientation of the immobilized antibody with the prevention of non-specific adsorption was achieved on the His6-protein A/PEG surface.
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In this study, three PEG-maleated rosin polyesters were produced by reacting between maleated rosin and PEG with different molecular weights and served as surfactants. The surface characteristics of these PEG-maleated rosin polyesters were detected. The conformational transition and adsorption characteristics of these polyesters were analyzed with the reorientation theory on the water–air surface. The surfactant mole fraction at the water–air surface increased as surfactant concentration increased, while the solvent mole fraction was decreased. The amount of surfactant on the water–air surface at state 1 with a maximal molar area appeared one unimodal in distribution and that at state 2 occupying a minimal molar area appeared a sigmoid distribution with П growth. The calculated adsorption free energy from CMC value is lower than calculated micellization energy obtained from molecular area at state 2 indicates the polyethylene glycol-maleated rosin polyesters firstly spread on the water–air surface and then aggregated into micelles. The results lay a foundation for better understand the adsorption and self-assembly processes. Graphical abstract The adsorption characteristics and conformational transition of three PEG-maleated rosin polyesters were investigated. Paper title: Adsorption Characteristics and Conformational Transition of Polyethylene Glycol-maleated Rosin Polyesters on the Water–Air Surface
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Polydiacetylene (PDA) vesicles provide useful stimuli-responsive behavior as well as by the modular structure afford a means for the design of sensing and delivery systems with tunable target specificity. To reduce inherent non-specific interaction with either anionic or cationic formulations of polydiacetylene vesicles, we explored the use of various lengths of poly(ethylene glycol) (PEG) amphiphiles for integration and polymerization within PDA vesicles. Our results established that as little as 1% of polyethylene glycol amphiphile integration into anionic vesicles was sufficient to significantly reduce non-specific association with mammalian cells. Similarly integrating a low percent of PEG amphiphile content within cationic vesicles could also significantly reduce non-specific cell association, and moreover reduced cytotoxicity. These results may be prove useful in augmenting PDA vesicles formulations for reduced non-specific interaction which is of particularly interest to enhancing selectivity in vesicles designed with integrated targeting moieties for sensing and drug delivery applications.
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Protein therapeutics have gained momentum in recent years and become a pillar in treating many diseases and the only choice in several ailments. Protein therapeutics are highly specific, tunable, and less toxic than conventional small drug molecules. However, reaping the full benefits of therapeutic proteins in the clinics is often hindered by issues of immunogenicity and short half‐life due essentially to fast renal clearance and enzymatic degradation. Advances in polymer chemistry and protein engineering allowed overcoming some of these limitations. Strategies to prolong the half‐life of proteins rely on increasing their size and stability and/or fusing them to endogenous proteins (albumin, Fc fragment of antibody) to hijack physiological pathways involved in protein recycling. On the downside, these modifications might alter therapeutic proteins structure and function. Therefore, a compromise between half‐life and activity is sought. This review covers half‐life extension strategies using natural and synthetic polymers as well as fusion to other proteins and sheds light on genetic engineering strategies and chemical and enzymatic reactions to achieve this goal. Promising strategies and successful applications in the clinics are highlighted. In the past decades, breakthroughs in protein engineering strategies have revolutionized the development of long‐acting medicines. Conjugation of polymers, polypeptides, Fc antibody fragments or human serum albumin to a parent therapeutic protein increases its half‐life and modulates protein biological activity.
Article
Surface-active linear and star-shaped miktoarm polymers containing cholic acid as a bile acid derivative are prepared by esterification of poly(ethylene glycol methyl ether) and subsequent ring-opening polymerization of epsilon caprolactone, respectively. The chemical structures, molecular characteristics and thermal properties of obtained polymers are clearly confirmed by FT-IR, 1H-NMR, GPC, DSC and TGA analysis. The presence of characteristic bands of cholic acid, ether and ester groups in FT-IR and 1H-NMR spectroscopies is proof of the successful synthesis of linear and star-shaped polymers. The melting point of star-shaped polymer is slightly lower than the linear polymer. Additionally, their surface activity properties have been investigated by AFM, SEM and contact angle studies and it is found that they can be self-assembled into micelles. Furthermore, the size of the micelles and contact angle properties has been changed with the addition of both hydrophilic (poly(ethylene glycol)) and hydrophobic (poly(epsilon caprolactone)) blocks on the cholic acid head. It is also clearly seen the effect of hydrophobic poly(epsilon caprolactone) functions increased contact angle and surface tension values after the formation of star-shaped polymer.
Chapter
In the last chapter, Das and Das have presented the advantages of biodegradable polymeric nanoparticles in biomedical use, and have also provided an overview of general methods of fabricating and designing nanoparticles. In this chapter, we will continue to talk about nanoparticles as carriers of therapeutics, but will narrow down the focus of the discussions to the context of neurological aging. In fact, neurological disorders such as Parkinson’s disease, Alzheimer’s diseases, neuropathic pain, and cerebrovascular accidents affect approximately 1.5 billion people globally. Over the years, an array of bioactive molecules have been found to be effective for the treatment of neurological conditions but not to be clinically effective due to the presence of the blood–brain barrier (BBB). The BBB is primarily responsible for the separation of extracellular fluid and blood within the CNS, generating a selectively permeable barrier restricting the passage of an array of substances, such as drugs, biomolecules, and potentially pathogenic substances. Nanomedicine is an attractive non-invasive technology that can be employed to circumvent this barrier. In this chapter, we will review the current advancements and limitations for the employment of nanomedicine to treat neurological diseases, and will also delineate the clinical and regulatory requirement for market entry of these products.
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The process of wound healing includes four phases: Hemostasis, inflammation, proliferation, and remodeling. Many wound dressings and technologies have been developed to enhance the body's ability to close wounds and restore the function of damaged tissues. Several advancements in wound healing technology have resulted from innovative experiments by individual scientists or physicians working independently. The interplay between the medical and scientific research fields is vital to translating new discoveries in the lab to treatments at the bedside. Tracing the history of wound dressing development reveals that there is an opportunity for deeper collaboration between multiple disciplines to accelerate the advancement of novel wound healing technologies. In this review, we explore the different types of wound dressings and biomaterials used to treat wounds, and we investigate the role of multidisciplinary collaboration in the development of various wound management technologies to illustrate the benefit of direct collaboration between physicians and scientists.
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Derivatives of poly(ethylene glycol) (PEG) are of importance in a variety of applications. Often it is difficult to determine the identity of the end groups and the purity of these derivatives. In the present work we show that proton NMR spectra of PEGs dissolved in deuterated dimethyl sulfoxide (but not other solvents) reveal a hydroxyl peak at 4.56 (±0.02) ppm, which does not shift or broaden with variation in concentration of the PEG, water, or impurities and which is well separated from the large backbone resonance. The hydroxyl resonance in other solvents does not show this independence, and thus it is difficult to locate and utilize. The PEG hydroxyl resonance for samples in dimethyl sulfoxide is, therefore, well suited for quantifying percent substitution and molecular weight of PEG and derivatives. Use of this method is illustrated.
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Methoxypolyethylene glycols of 1900 and 5000 daltons have been attached covalently to bovine serum albumin using cyanuric chloride as the coupling agent. When sufficient polymer is attached, the modified bovine serum albumin appears to lose its immunogenicity in the rabbit and, on intramuscular or intravenous injection, elicits antibodies neither to itself nor to native bovine serum albumin. It does not react with antibodies raised against native bovine serum albumin. Bovine serum albumin to which methoxypolyethylene glycol has been attached exhibits a blood circulating life in the rabbit rather similar to native bovine serum albumin, except that it is not removed from circulation by the eventual development of antibodies. Modified bovine serum albumins which had been iodinated with 125I, or prepared with [14C]cyanuric chloride, were injected intravenously in rabbits. Both labels appeared almost quantitatively in the urine after 30 days. The modified bovine serum albumins showed substantial changes in properties, such as solubility, electrophoretic mobility in acrylamide gel, ion exchange chromatography, and sedimentation, as compared with the unmodified protein.
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A simple, rapid and high-yielding method for the synthesis of oligonucleotides by the phosphotriesters approach Is described. The use of polyethylene glycol (PEG) as soluble polymeric support preserves some convenient features of the solid-phase synthesis with new interesting advantages.Short oligonucleotides in hundred milligrams scale can be obtained from few grams of functionalised PEG.
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Recombinant human interleukin 2 purified from Escherichia coli has limited solubility at neutral pH and a short circulatory half-life. This recombinant interleukin 2 was chemically modified by an active ester of polyethylene glycol. The modified interleukin 2 was purified by hydrophobic interaction chromatography and characterized by sodium dodecyl sulfate/polyacrylamide gel electrophoresis and isoelectric focusing. This conjugate was compared to unmodified recombinant interleukin 2 in vitro and in vivo. Covalent attachment of the hydrophilic polymer polyethylene glycol enhanced the solubility of interleukin 2, decreased its plasma clearance, and increased its antitumor potency in the Meth A murine sarcoma model.
Chapter
Polyethylene glycols (PEG’s) and their derivatives are finding a rapidly expanding range of chemical, biomedical, and industrial applications resulting from their low cost and useful properties such as solubility in aqueous and organic solvents, metal complexing ability, biological compatibility, and ease of chemical modification. The linear polymers have been employed as soluble matrices for liquid-phase peptide synthesis,2 ligands for water-soluble transition metal complexes,3 drug carriers,4 water-soluble cell fusion agents.5 Other reasons for the current interest in PEG’s include their reduction of enzyme immunogenicity,6 and their utility in aqueous two-phase polymer cell separations (phase partitioning).7
Article
The effects of polyethylene-glycol (PEG) substitution on protein activity, us ing alkaline phosphatase as a model, have been studied. Such variables as PEG molecular weight, degree of substitution, and PEG mono- and di-functionality have been examined. Modification with the monomethyl ether of PEG 1900 (M- PEG-1900) does not alter enzyme activity until greater than 40% of the protein lysine groups are substituted, at which point increasing the degree of modifica tion gives increasing deactivation. Substitution with M-PEG-5000 gives more deactivation than does substitution with M-PEG-1900. Interestingly, modifica tion with PEG itself gives active protein conjugates in which there is little de pendence on molecular weight or degree of substitution.
Article
Interspecific and intergeneric fusions of plant protoplasts were induced by polyethylene glycol (PEG) 1540 or 4000. The frequency of heterokaryocyte formation (or rate of fusion) was much higher when PEG was eluted with a high pH-high Ca2+ solution or a salt solution than when it was eluted with a protoplast culture medium. The frequency of heterokaryocyte formation was also affected by the types of enzymes used for wall degradation, duration of enzyme incubation and molality of the PEG solutions. The maximum frequency of heterokaryocyte formation was 23% for V. hajastana Grossh.-soybean (Glycine max L.) and barley (Hordeum vulgare L.)-soybean, 35% for pea (Pisum sativum L.)-soybean, 20% for pea-V. hajastana, 14% for corn (Zea mays L.)-soybean and 10% for V. villosa Roth-V. hajastana. 40% of the barley-soybean, corn-soybean and pea-soybean heterokaryocytes divided at least once. Some divided many times and formed clusters of up to 100 cells in 2 weeks. The heterokaryocytes of soybean-V. hajastana, V. villosa-V. hajastana also divided. Of the PEG-treated protoplasts of N. langsdorffii and N. glauca 13.5% developed into tumor-like calli. The morphology of these calli was very much like that of the tumors produced on amphidiploid plants of N. langsdorffii x glauca. Nuclear staining indicated that heterokaryocytes of V. hajastana-soybean, pea-soybean, corn-soybean and barley-soybean could undergo mitosis. Nuclear divisions in a heterokaryocyte were usually synchronized or almost synchronized. Nuclear fusion and true hybrid formation usually occurred during the first mitotic division after protoplast fusion. A hybrid of barley-soybean in third cell division was observed. The frequency of heterokaryocytes which underwent nuclear fusion has not been determined. Multipole formation and chimeral cell colonies were also observed.
Article
In gel chromatographic experiments using Sephadex G-200, human serum albumin has been chromatographed in eluents containing neutral polymers. Each of the four types of polymers studied; dextran, polyethyleneglycol, polyvinylalcohol, and Ficoll, was tested at several concentrations. Albumin is eluted later as the polymer concentration in the eluent is increased. This is ascribed to an activity increase of the protein in the mobile polymer phase that is due mainly to steric exclusion. When the exclusion properties of the gel phase are known one can calculate the exclusion of the test substance from the liquid polymer phase. Measurements made by this method agree well with data derived from solubility studies of the exclusion of albumin from dextran solutions. They agree exactly with the exclusion measurements on dextran gels. The method should be useful in studies of the exclusion properties and the molecular parameters of polymer solutions.
Article
The literature data on the use of poly(ethylene glycol) (PEG) in biochemistry and molecular biology are analysed from the standpoint of the physical chemistry of polymers. The exclusion properties of PEG, used as a factor influencing the rate of enzymatic reactions, the intra- and intermolecular transitions in polymers, and biopolymer precipitation and crystallisation processes are examined. The suitability of three-component PEG–dextran–water mixtures for the purification and separation of mixtures of biopolymers and for analytical purposes as well as the possibility of using functional derivatives of PEG in immunological research and for the immobilisation of enzymes are discussed. A special section is devoted to the synthesis of PEG derivatives containing different functional groups at the ends of the polymer chain. The surface-active properties of PEG are examined. The bibliography includes 78 references.
Article
Aqueous systems with two soluble polymers often phase-separate into two isotropic solutions. We investigate the molecular mechanism leading to this phase separation. It is concluded that the important factor is the direct molecular interaction between the monomeric units of two polymers, which should be effectively repulsive for phase separation to occur. Previously it has also been suggested that the size and shape of the entire polymer molecules are important factors, but our analysis does not support this view.
Article
Proteins can be modified chemically by attaching synthetic or natural macromolecules to the surface of the protein molecule. In some cases, this manipulation of protein modification with polymers can eliminate some drawbacks of native proteins and improve thier properties. These are important aspects for future application in the use of protein drugs and catalysts in bioreactors. Poly(ethylene glycol) (PEG) with a history of plasma expander, being nonimmunogenic, amphipathic and nontoxic, has been applied to various enzymes as a superior agent for modification. This report is focused on our recent work with poly(ethylene glycol)-protein conjugates and their potential medical aplications.
Article
One hundred and one rats were administered either D, α-tocopheryl succinate plus polyethylene glycol (PEG), PEG, or saline 30 min prior to or 5 min after moderate fluid percussion brain injury. Mortality rates, performance on beam balance and beam-walking tasks, and body weight were assessed daily for 10 days. With preinjury administration, mortality rate was reduced from 31% with saline to 9% with PEG and 9% with D, α-tocopheryl succinate plus PEG. With postinjury administration, mortality rate was reduced from 36% with saline to 20% with PEG and to 10% with the D, α tocopheryl succinate plus PEG combination. With administration prior to injury, PEG and D, α-tocopheryl succinate plus PEG reduced the deficits seen on beam balance testing on days 1-3 after injury. On beam walking, PEG and D, α tocopheryl succinate plus PEG reduced deficits compared to those in saline-injected animals on days 1 and 2 and on day 1 after injury, respectively. A strongly protective effect of PEG and of D, α-tocopheryl succinate plus PEG was seen with preinjury administration. With postinjury administration, D, α-tocopheryl succinate plus PEG reduced deficits on beam balance testing compared to animals receiving both saline and PEG on days 1-3 after injury. On beam-walking latencies, D, α-tocopheryl succinate plus PEG reduced deficits on days 1 and 2 after injury compared to saline and to PEG. Both PEG and D, α-tocopheryl succinate plus PEG reduced weight loss after injury compared to saline. The protective effects of these agents and their relatively low toxicity and high lipid solubility give them potential for the treatment of human head injury.
Conference Paper
This book presents papers given at a symposium of the American Chemical Society. Topics covered include: Aromatic substitution in condensation polymerization catalyzed by solid-liquid phase transfer; Triphase catalysis in organometallic anion chemistry; and Multisite phase-transfer catalysts.
Article
POLYETHYLENE glycol is now widely used for concentrating protein solutions by dialysis. We have used the material of molecular weight 15,000 (L. Light and Co., Ltd., Colnbrook, England) and have found that it penetrates dialysis sacs to an appreciable extent.
Article
In recent years, derivatives of polyethylene glycol (PEG) have proven valuable in a variety of diverse chemical and biological endeavors. Such applications include peptide synthesis, phase transfer catalysis, pharmaceutical modification, protein and cell purifications, polymer-bound reagents, and binding assays. Because of the great deal of interest surrounding this subject, this review will describe generally applicable laboratory methods for preparing PEG derivatives from the parent PEG. We have largely restricted discussion to this starting material because most research laboratories interested in applications are not equipped to handle complex ethylene oxide polymerizations used in large-scale industrial preparations and because PEG and some of its ethers and esters are the only commonly available polymeric starting materials. For the purpose of this review, PEG is defined as those polyoxyethylenes having hydroxyl endgroups and a molecular weight of 20,000 daltons or less.
Article
Vapor pressures at 25°C are reported for binary aqueous solutions containing 5-40 wt % poly(ethylene glycol) (PEG) 3350 or PEG 8000 or Dextran T-70 or Dextan T-500. 'Effective' osmotic second virial coefficients are calculated from vapor-pressure data at concentrations below 15 wt %. These are somewhat larger than second virial coefficients obtained from low-angle laser-light-scattering (LALLS) measurements at high dilution, indicating contributions from higher order interactions. Vapor-pressure data are used together with osmotic second virial coefficients measured by LALLS to fit an 'effective' third virial coefficient for each binary system. Chemical potentials obtained from vapor-pressure and LALLS data are used to predict liquid-liquid equilibria (LLE) for aqueous ternary systems containing PEG and dextran. Predicted and measured LLE are in good agreement.
Article
The partitionings of five proteins - lysozyme, chymotrypsinogen, ovalbumin, human serum albumin, and bovine serum albumin - in two phase systems made from poly(vinyl methyl ether) (PVME) and poly(ethylene oxide) (PEO) were examined as functions of the compositions of the systems. Chymotrypsinogen partitioning was also examined as a function of PEO molecular weight. Experimental data for the partition coefficients were compared with values calculated from the lattice model of J.N. Baskir et al. Calculations were in good agreement with the experiments over the range of conditions investigated. Estimated phase polymer concentrations near the proteins were generally lower than those in the bulk, indicating that partitioning is primarily governed by steric repulsion of the protein from the phase polymers.
Article
Analytical particle microelectrophoresis was used to evaluate the effectiveness of various coatings for control of the electroosmotic fluid flow that hinders electrophoretic processes. Mobilities of 2-μm-diameter glass and polystyrene latex spheres, exhibiting both negative and zero effective surface charge, were measured in 2-mm-diameter quartz capillaries filled with NaCl solutions within the pH range of 3.5 to 7.8. Covalent coating of capillary inner surfaces with poly(ethylene glycol) caused a reduction in the degree of electroosmotic flow which was related to the poly(ethylene glycol) molecular weight. Poly(ethylene glycol) coatings of 5000 molecular weight, or higher, greatly reduced electroosmosis within the selected pH range, were stable for long periods of time, and appeared to be more effective than dextran, methylcellulose, or silane coatings. Because of these characteristics, poly(ethylene glycol) coatings should be of considerable use for improving various electrophoretic processes as well as in the production of standard particles exhibiting controlled electrophoretic mobilities.
Article
Polyethylene glycol (PEG) was used as a carrier polymer for the attachment, via end groups, of drugs such as penicillin V, aspirin, amphetamine, quinidine and atropine. For this purpose, methods were developed for the functionalization of PEG; PEG-NH2, PEG-COOH and PEG-NCO were prepared. Use was made of dicyclohexyl carbodiimide together with 4-dimethylamino pyridine or 1-hydroxybenzotriazole for the coupling reactions.
Article
WE report new findings on the chemically-induced fusion of hen erythrocytes and discuss possible ways in which the lipid and protein/glycoprotein components of membranes may behave during the process of membrane fusion. Our observations are consistent with Poste and Allison's1 idea that the aggregation of intrinsic membrane proteins is important in membrane fusion but we suggest that fusion may occur in regions of perturbed lipid bilayer which are thus denuded of intramembranous particles.
Article
Polyethylene glycol (PEG) is known to promote fusion of plant protoplasts. Various adaptations of this treatment to mammalian, including human, cell cultures are reported here. PEG is very effective in producing hybrids capable of indefinite multiplication even in cases, such as early passage human skin fibroblasts and lymphocytes, known to be highly recalcitrant to other treatments.
Article
Well-defined liposome systems have previously established the influence of size, surface charge lipid composition and surface ligands, on in vivo fate and behaviour of model compounds entrapped in liposomes. In the present study, preformed liposomes which quantitatively retain aqueous markers were covalenty coupled via dipalmitoylphosphatidyl-ethanolamine, to the hydrophilic polymer, monomethoxypoly(ethylene glycol) (MPEG 5000). Such liposomes retain the coating in the presence of plasma, and appear to adsorb plasma components more slowly than liposomes without the polymer, shown using an aqueous two-phase partitioning technique. MPEG-coupled liposomes were cleared from the blood circulation up to 30% more slowly than liposomes without MPEG after intravenous administration to mice, despite the unmodified liposomes being of a composition and size shown previously to favour achievement of maximum half-life. It is suggested that the polymer acts as a surface barrier to plasma factors which otherwise bind to liposomes in the blood and accelerate vesicle removal.
Article
Dioleoyl-N-(monomethoxy polyethyleneglycol succinyl)-phosphatidylethanolamine (PEG-PE) (mol. wt. of PEG = 5000), an amphipathic polymer, can be incorporated into the liposome membrane and significantly prolong the blood circulation time of the liposome. As little as 3.7 mol% of PEG-PE in liposome resulted in maximal enhancement of liposome circulation time. However, this activity of PEG-PE was only seen with relatively small liposomes (d less than or equal to 200 nm); larger liposomes containing PEG-PE showed an unusually high level (approx. 35% injected dose) of accumulation in the spleen. We have tested whether the small, PEG-PE containing liposomes are suitable for immuno targeting by incorporating a lung-specific monoclonal antibody on the liposome surface. While another amphiphile, ganglioside GM1, which is well known for its activity to prolong the liposome circulation time, significantly enhanced the lung binding of the immunoliposomes, PEG-PE incorporation of immunoliposomes resulted in a low level of target binding. To test if the reduced target binding is due to a steric barrier effect of the surface PEG polymer, we have incorporated a small amount of N-biotinaminocaproylphosphatidylethanolamine into the PEG-PE containing liposomes and examined the liposome agglutination induced by the addition of streptavidin. As little as 0.72 mol% PEG-PE in these liposomes completely abolished agglutination. In contrast, incorporation of GM1 in liposomes only reduced the rate, but not the extent, of liposome agglutination. These results strongly support the hypothesis that PEG-PE prolongs liposome circulation time by providing a strong steric barrier which prevents close contact with another liposome or cell. Since GM1 provides only a weak steric barrier effect, its activity to prolong the liposome circulation time must involve another yet unknown mechanism.
Article
We are able to morphologically fuse the severed halves of an invertebrate-myelinated axon by application of polyethylene glycol (PEG) to closely apposed cut ends. Morphological fusion of the medial giant axon (MGA) of the earthworm Lumbricus terrestris is defined as axoplasmic and axolemmal continuity in serial longitudinal sections of MGAs taken through the fusion site as viewed with light or electron microscopes. Morphological continuity is also shown by the transfer of Lucifer yellow dye between apposed MGA segments fused with PEG, but not between apposed MGA segments in normal or hypotonic saline without PEG application. PEG-induced MGA fusion rates can be as high as 80-100% with an appropriate choice of PEG concentration and molecular mass, tight apposition and careful alignment of the cut ends, and treatment with hypotonic salines containing reduced calcium and increased magnesium. A variant of this technique might produce rapid repair of severed mammalian-myelinated axons.
Article
The mechanism of poly(ethylene glycol)-induced fusion of phospholipid vesicles was studied based on the "osmophobic association" theory which was recently proposed both theoretically [Ito, T., Yamazaki, M., & Ohnishi, S. (1989) Biochemistry 28, 5626-5630] and also experimentally [Yamazaki, M., Ohnishi, S., & Ito, T. (1989) Biochemistry 28, 3710-3715]. Osmophobic association and fusion were detected by measuring the light scattering of the vesicle suspension; the former was detected from the increase in light scattering induced by the addition of PEG, and the latter was from the irreversibility of the increase in light scattering. Threshold concentrations of PEG were required not only for osmophobic association but also for fusion. The threshold concentration for fusion depended on the molecular weight of PEG and also on the electrostatic repulsive interaction between phospholipid vesicles, which was manipulated by the use of vesicles with negative surface charge; increasing the molecular weight of PEG lowered the threshold concentration, and increasing the electrostatic repulsive interaction raised it. In addition, a transient leakage of internal contents from the vesicles was observed at the concentration that caused fusion. When the surface charge of the vesicle was varied, the threshold for fusion coincided with that for osmophobic association, provided that the latter exceeded 22 wt % of PEG 6000. However, when the threshold for osmophobic association was less than 22 wt %, the threshold for fusion remained approximately 22 wt %, irrespective of the difference in the threshold for osmophobic association.(ABSTRACT TRUNCATED AT 250 WORDS)
Article
New phase supports for liquid-liquid partition chromatography, using aqueous poly(ethyleneglycol)-dextran systems have been developed by grafting linear polyacrylamide chains on to premanufactured chromatographic supports carrying primary or secondary aliphatic hydroxyl functions on their surface. Columns prepared from such supports have a higher binding capacity for the dextran-rich stationary phase and much higher performances than columns prepared from cellulose, the previously used phase support for this system. Test separations of DNA restriction fragments, ranging from 11 base pairs to 3829 base pairs, document a high resolution for DNA fragments larger than 200 base pairs.
Article
A method to evaluate in blood free superoxide dismutase (SOD) and SOD covalently bound to monomethoxypolyethylene glycol (MPEG-5000) is reported. The method takes advantage of gel filtration and cationic exchange chromatography to remove substances present in plasma which can interfere with the SOD enzymatic assay. Using this methodology, it was demonstrated that, contrary to free SOD, MPEG-SOD, when added to blood, was not completely recovered in plasma. Binding of MPEG-SOD to blood cell components takes place involving interactions of MPEG chains with cell membranes.
Article
The present studies were undertaken to investigate the enzymology of a fatal toxic syndrome that resulted from the absorption and subsequent oxidation of polyethylene glycol (PEG). The presence of organic acids of PEG in the blood of poisoned patients and in an animal model suggested that the metabolism of PEG involved sequential oxidations by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase. A key question concerned the ability of ADH to initiate this pathway for oxidation of PEG. In the present studies the oxidation of PEG homologues by ADH was characterized. The polymer homologues of ethylene glycol from n = 1 to n = 8 were used as substrates. ADH catalyzed the oxidation of each of these PEGs. The oxidation of PEG was inhibited by the ADH inhibitor 4-methylpyrazole. With the exception of diethylene glycol, the Km decreased as the homologue number increased, and the Vmax decreased progressively through the series. The concentrations of PEG in the blood of poisoned humans and animals were 0.06 to 0.8 Km of ADH for all the PEG homologues above the triethylene glycol. These investigations establish ADH as a candidate enzyme for mammalian metabolism of PEG and thus suggest that specific inhibitors of ADH may prove to be useful as tools to treat PEG poisoning.
Article
Fusion of synaptic vesicles with the surface membrane of the nerve terminal is a key step in synaptic transmission, which normally requires the entry of calcium ions into the cell. We report that this fusion and the subsequent liberation of transmitter can also be induced by the fusogenic substances DMSO (dimethyl sulfoxide) and PEG (poly(ethylene glycol)). Calcium ions and DMSO exhibit a synergistic effect in the fusion of synaptic vesicles with the axolemma, resembling their action on fusion phenomena in liposomes.
Article
Previous work has shown that polyethylene glycol (PEG)-bound antibodies can be used as affinity ligands in PEG-dextran two-phase systems to provide selective partitioning of cells to the PEG-rich phase. In the present work we show that immunoaffinity partitioning can be simplified by use of PEG-modified Protein A which complexes with unmodified antibody and cells and shifts their partitioning into the PEG-rich phase, thus eliminating the need to prepare a PEG-modified antibody for each cell type. In addition, we provide a more rigorous test of the original technique with PEG-bound antibodies by showing that it is effective at shifting the partitioning of either cell type of a mixture of two cell populations.
Article
Severed medial giant axons in crayfish can be rejoined in vitro with polyethylene glycol (PEG) to produce axoplasmic continuity and through transmission of action potentials. Severed axon-like processes of a mammalian neuroblastoma/glioma cell line seem to be rejoined to the cell body using PEG in tissue culture. Our data suggest that PEG might be used to rejoin severed axons in vivo in various organisms.
Article
We treated two children who had adenosine deaminase deficiency and severe combined immunodeficiency disease by injecting bovine adenosine deaminase modified by conjugation with polyethylene glycol. The modified enzyme was rapidly absorbed after intramuscular injection and had a half-life in plasma of 48 to 72 hours. Weekly doses of approximately 15 U per kilogram of body weight maintained plasma adenosine deaminase activity at two to three times the level of erythrocyte adenosine deaminase activity in normal subjects. The principal biochemical consequences of adenosine deaminase deficiency were almost completely reversed. In erythrocytes, adenosine nucleotides increased and deoxyadenosine nucleotides decreased to less than 0.5 percent of total adenine nucleotides. The activity of S-adenosylhomocysteine hydrolase, which is inactivated by deoxyadenosine, increased to normal in red cells and nucleated marrow cells. Neither toxic effects nor hypersensitivity reactions were observed. In vitro tests of the cellular immune function of each patient showed marked improvement, along with an increase in circulating T lymphocytes. Clinical improvement was indicated by absence of infection and resumption of weight gain. We conclude that from the standpoints of efficacy, convenience, and safety, polyethylene glycol-modified adenosine deaminase is preferable to red-cell transfusion as a treatment for adenosine deaminase deficiency. Patients with other inherited metabolic diseases in which accumulated metabolites equilibrate with plasma could benefit from treatment with the appropriate polyethylene glycol-modified enzyme.
Article
By the use of fractional precipitation with high molecular weight nonionic polymers, immune globulins of marked homogeneity were isolated in high yield from either whole serum or commercial samples of immunoglobulins. The isolated fractions were characterized by immunochemical and ultracentrifugal analyses. When the pH was varied from 4.9 to 8.6 and the ionic strength from 0.1 to 2.0, little effect on the precipitation of the immunoglobulins was noted. The immunochemical studies indicated that this fractionation technique is not effective in separating the γG, γM, and γA activities present in the γ-globulins isolated from whole serum or in commercial immunoglobulin preparations.Preliminary experiments indicate that this technique may be used for the isolation of other serum proteins, especially albumin and the α-globulins. In these instances, however, it is important that ionic strength and pH be controlled.The mechanism for the precipitation of serum proteins by PEG has not been established, but it is suggested that the precipitation involves a local dehydration and consequent change in the dielectric constant of the medium immediately surrounding the protein molecules.It would appear that the high-polymer precipitation technique may be an effective and simple method for the isolation of serum proteins with preservation of much of their native properties.
Article
. Intermediate- and high-purity antibaemophilic factor (factor-VIII) concentrates developed by the American National Red Cross (ANRC) have undergone extensive clinical investigation. When administered to severely affected haemophiliacs, the recovery in vivo and the metabolic half-disappearance time were similar to those achieved with plasma.
Antibodies to polyethylene glycol (PEG) were raised in rabbits by immunization with monomethoxy polyethylene glycol modified ovalbumin (OA), bovine superoxide dismutase (SOD), and ragweed pollen extract (Rag), given in Freund's complete adjuvant (FCA). Immunogenicity depended on the nature of the protein and the degree of modification. With modified OA, in the presence of FCA, the majority of animals showed an anti-PEG response. With modified SOD and Rag only a small proportion of animals responded. In the absence of FCA, modified OA, given s.c., did not elicit any anti-PEG antibody response in rabbits and only a weak response in mice. PEG of MW 10,000 and 100,000 given in FCA was found nonimmunogenic in rabbits, and PEG of MW 5.9 X 10(6), given s.c. to mice, showed no or very poor immunogenic properties. Gel diffusion, heterologous passive anaphylaxis and passive hemagglutination were used to demonstrate anti-PEG antibodies raised to PEG-modified proteins. Specificity was confirmed by hapten inhibition of precipitation, inhibition of passive hemagglutination and cross-reactivity tests. PEG of MW greater than or equal to 4,000 produced specific precipitates, smaller molecules acted as monovalent haptens. From hapten inhibition of precipitation by PEG of MW 300 it appears that the antigenic determinant of PEG may be a sequence of 6-7 -CH2CH2O-units. Anti-PEG antibodies can be used analytically. By gel diffusion, Peg was detected in minimal concentrations of 0.1-1 microgram/ml. The clinical relevance of these findings with regard to therapy with PEG-modified enzymes and allergens in humans remains to be established.
Article
The covalent attachment of monomethoxypolyethylene glycol (PEG) to asparaginases from Escherichia coli and Vibrio succinogenes by new coupling methodology produced conjugates that are active, stable, without significant immune response, and with greatly extended plasma half-lives in mice. Therapeutic efficacies were greater for the PEG-asparaginases than for the unmodified asparaginases in mice infected with the L5178Y lymphosarcoma or the 6C3HED tumor. Large single doses of native or modified enzymes were more effective against tumors than the same amount of enzyme given in smaller doses over several days.
Article
Various aspects of the interaction between the fusogen, poly(ethylene glycol) and phospholipids were examined. The aggregation and fusion of small unilamellar vesicles of egg phosphatidylcholine (PC), bovine brain phosphatidylserine (PS) and dimyristoylphosphatidylcholine (DMPC) were studied by dynamic light scattering, electron microscopy and NMR. The fusion efficiency of Dextran, glycerol, sucrose and poly(ethylene glycol) of different molecular weights were compared. Lower molecular weight poly(ethylene glycol) are less efficient with respect to both aggregation and fusion. The purity of poly(ethylene glycol) does not affect its fusion efficiency. Dehydrating agents, such as Dextran, glycerol and sucrose, do not induce fusion. 31P-NMR results revealed a restriction in the phospholipid motion by poly(ethylene glycol) greater than that by glycerol and Dextran of similar viscosity and dehydrating capacity. This may be associated with the binding of poly(ethylene glycol) to egg PC, with a binding capacity of 1 mol of poly(ethylene glycol) to 12 mol of lipid. Fusion is greatly enhanced below the phase transition for DMPC, with extensive fusion occurring below 6% poly(ethylene glycol). Fusion of PS small unilamellar vesicles depends critically on the presence of cations. Large unilamellar vesicles were found to fuse less readily than small unilamellar vesicles. The results suggest that defects in the bilayer plays an important role in membrane fusion, and the 'rigidization' of the phospholipid molecules facilitates fusion possibly through the creation of defects along domain boundaries. Vesicle aggregation caused by dehydration and surface charge neutralization is a necessary but not a sufficient condition for fusion.
Article
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