Introduction
Polyethylene glycol (PEG) is a popular, widely-used polymer consisting of repeated ethylene glycol units [CH2CH2On] (Wang et al., 2022). Due to its versatility, tunable properties and well-established safety profile, it plays an important role in various fields (Jafarpour, Fathi, & Soltanizadeh, 2023) as solubilizers, dispersion agents, emulsifiers, stabilizers, taste-masking materials, functional carrier, delivery controller, release-modifiers, texture promoter, bioavailability enhancers, etc.
As a USFDA-approved polymer (GRAS), it has been explored in medical application and food (additives, packaging, etc.) applications. PEG is also approved by Chinese Standards (food additives) in coating food like candy and chocolate products. PEG could be applied as pharmaceutical additives, and it is widely used as a hydrophobic/hydrophilic drug carrier to promote aqueous solubility, dissolution and stability (Ibrahim et al., 2022). Although PEG and its derivatives are considered inert and almost non-toxic
Molecules, some safety concerns may remain for PEG (Knop, Hoogenboom, Fischer, & Schubert, 2010). Its toxicity depends on several characteristics including molecular weights, concentrations, features, existence form and so on (Ibrahim et al., 2022). For instance, PEG 200 is generally considered to be harmless when applied orally or dismally to the undamaged skin, while it can be toxic when it is intraperitonially injected and is painful for the recipient mice, i.e., injections of pure, undiluted PEG are not safe at a dose of 8 mL/kg, and cause pain even at a dose of 2 mL/kg (Thiele, Kyjacova, Köhler, & Sleeman, 2019).
In addition, high concentrations of PEG 1000, PEG 4000, and mega 950 shows moderate cytotoxicity (Liu et al., 2017). In some literature, it is found that PEG could be excreted directly, especially in the common forms of urine materials and routine feces, after consumption by human body (Turecek & Siekmann, 2020), which could even reduce the toxicity of highly-concentrated bioactive, facilitate the long-term stability of bioactive molecules and promote the half-lives of bioactive materials (Turecek & Siekmann, 2020).
Abstract
interactions (amino groups, carboxyl groups, aldehyde groups, tosylate groups, etc.), and non-covalent bond interactions (hydrogen bonding, electrostatic interactions, etc.) on PEG molecular chains are discussed. Its versatile structure, group modifiability, and amphiphilic block buildability could improve the functions of polysaccharides (e.g., chitosan, cellulose, starch, alginate, etc.)
And adjust the properties of combined PEG/polysaccharides with outstanding chain tunability and matrix processability owing to plasticizing effects, compatibilizing effects, steric stabilizing effects and excluded volume effects by PEG, for achieving the diverse performance targets. The synergetic properties of PEG/polysaccharides with remarkable architecture were summarized, including mechanical properties, antibacterial activity, antioxidant performance, self-healing properties, carrier and delivery characteristics. The PEG/polysaccharides with excellent combined properties and embeddable merits illustrate potential
applications including food packaging, food intelligent indication/detection, food 3D printing and nutraceutical food absorption.
1. About Polyethylene Glycol (PEG) 4000, Granular, Lab Grade, Kosher
Polyethylene Glycol, (C2nH4n+2On+1), is synthesized by ring-opening polymerization of ethylene oxide. This synthesis process gives PEG a range of molecular weights and distributions from 300 grams per mole to 10,000,000 grams per mole.
PEG 4000 has a molecular weight of 4000 and is colorless, inert, odorless, and non-volatile. PEG is biocompatible (it won’t damage tissues or cells), hydrophilic, dissolves readily in water without changing the color odor or taste, and is nontoxic.
The number 4000 mentioned with the Polyethylene Glycol 4000, describes its average molecular weight. Lab-grade chemicals possess reasonable purity but do not comply with any official standard for quality or purity. It is recommended to use Lab Alley’s Polyethylene Glycol 4000, Lab Grade be used in training institutes, research labs, and for other commercial applications.
2. Benefits & Applications
Polyester grade EG is used in the manufacture of polyester fibers and polyethylene terephalate (PET) resins, used in making a number of products including textiles, tire cords, video tapes, and soft drink and water containers. LyondellBasell polyester EG meets the highest quality standards.
Hi-purity and industrial grade EG is used in a variety of applications requiring good solvent, hygroscopic or high boiling point characteristics, such as paints, printing inks, hydraulic fluids, cleaners, heat transfer fluids, and electronics. Antifreeze grade EG is a major component in the manufacture of automotive engine coolants.
- SURF ACE PATTERNS OF NEURAL ADHESION PEPTIDES ON A POLY(ETHYLENE GLYCOL)-BASED SURFACE TOWARD TWO-DIMENSIONAL ARTIFICIAL NEURAL NETWORKS INTRODUCTION
As a prelude to the work in three dimensions to be described in Chapters 4, 5, and 6, the aim of the work presented in this chapter was to photo-immobilize multiple cell adhesion peptides in a patterned fashion on an otherwise protein-and cell-adhesion resistant surface in order to effect localized adhesion, directed neurite outgrowth, and controlled synapse formation among groups of individual neurons in two dimensions.
The envisioned neural circuits were intended to provide in vitro models of neuronal behavior including development, nerve regeneration, and learning, and to allow for applications such as biosensors and bioelectric devices. The adhesion-resistant culture substrate was a highly crosslinked polymer network of trimethylolpropane triacrylate (TMPTA) and pentaerythritol tetraacrylate (PET A) copolymerized with poly(ethylene glycol) a-monoacrylate w-monoethylether (PEGMA).
Due to the high content of pending PEG chains, the advantage of this substrate material compared to many other surfaces was its persistent resistance to protein adhesion, therefore ensuring the preservation of a defined and controllable surface. In an initial test of principle, UV light-induced functionalization of this substrate was achieved with photolabel-derivatized RGDSG peptide in simple patterns, to which human fibroblasts adhered RGD-specifically.
To achieve the adhesion of dissociated cells from the dorsal root ganglia (DRG) of embryonic chicks, which include sensory cells that belong to the class of pseudo-unipolar neurons whose axons have a central and a peripheral branch. 129 regions on the substrate material had to be derivatized with a combination of five peptides
- MOTIVATION FOR NEURONAL CULTURES ON PATTERNED SURFACES
The computational, cognitive, adaptive. and creative capacity of the brain is unparalleled even by the most advanced computers of our age. Accordingly, a further understanding of the cellular and molecular mechanisms underlying the development, information processing, and plasticity, i.e., learning, of the brain would continue to promote the design of advanced computational methods and devices.13o·13I
Moreover. devices that already incorporate neuronal components as computational units are under investigation (e.g., by Curtis et al .• 1994; IJ2 Kovacs et al., 1994; 133 etc.). While brain slice preparations have revolutionized the study of synaptic transmission, neuronal integration and long-term potentiation,l3o the operation of the nervous system is only understood to a
Control of the organization of neurons in defined and reproducible networks in culture promise the potential for new systems of study and for major technical innovation. 130 Toward the goal of culturing neurons in preCIse, reproducible and meaningful networks, the following requirements have to be met: A. Long-term viability of neurons in culture. B.
Well defined and invariable culture substrates that can be patterned. C. Directed growth of neural processes along defined pathways. D. Controlled neuronal polarity by orienting the growth of the axon and dendrites. £. Formation of functional synapses between patterned neurons. F.
Retention of differentiation state and transmitter phenotype of patterned neurons. (hased on Cotman et al., 1994; IJO modified)
The pnmary focus of the research described in this chapter was to contribute to an improvement and understanding of the issues pertaining to requirements A -C, which might lead to progress and insights regarding D, E and F.
That is, insights about the establishment of neuronal polarity, synapse formation, and determinants of neuronal differentiation in j’itro will be gained by studying the growth and behavior of neurons in culture as a function of precisely controlled surface chemistry and geometry. For instance,
- PREVIOUS WORK WITH PATTERNED SURFACES
Chemically Patterned Surfaces The patterning of surfaces lies at the heart of any effort to guide neural growth in two dimensions. The idea is to outline regions and “paths” for cell attachment and neurite extension on surfaces that are otherwise adhesion resistant or non-permissive of neural growth.
Ground-breaking progress in chemical patterning of surfaces has been made by Whitesides and co-workers (e.g., Kumar. 1994).134 Based on stamping or contact printing, self-assembled mono layers (SAMs) of alkanethiolates can be adsorbed on a gold surface in a patterned fashion on scales as small as 0.2 f.lm. An elastomeric stamp bearing the desired pattern is used to transfer alkanethiols with desirable functional end groups to the surface of an evaporation-deposited gold film.
A pattern consisting of chemically differentiated regions can thus be created at submicron-scale resolution.
- Shortcomings of Chemically Patterned Substrate Materials
The abundance of surface patterning techniques presently available has given rise to impressive short-ten control over the organization of various cell types on culture substrates by virtue of surface chemistry and geometry,l36.137 but most of the culture substrates used do not pen nit long-tenn control over the properties of the surface, as protein adsorption, desorption, denaturation, and proteolysis remain unpredictable variables. For instance, even when human or bovine serum albumin is pre-adsorbed on certain regions of a surface to render those regions resistant to cell adhesion by blocking them from other, adhesion-promoting, and albumin’s surface confrontation.
- Biospecific Patterned Surfaces
Recent attempts of surface patterning and fictionalization have been aimed at obtaining better defined culture substrates by employing short adhesion peptides based on extracellular-matrix proteins such as lamina, collagen, fibronectin and others (see Chapter 2).
Since short adhesion peptides are often less prone to proteolysis degradation and denaturation on surfaces, their use circumvents some of the complications resulting from using whole proteins to define surface properties. However, the problem of surface changes due to uncontrolled protein adsorption remains. Nevertheless, the advantage of employing individual adhesion-and outgrowth-promoting peptides is that the specific response to a particular isolated peptide can be tested.
- The Poly(Ethylene Glycol)-Containing Substrate Material
Besides resistance to protein adhesion, the substrate material must be mechanically robust and stable. Non-toxic for cell culture purposes, and preferably translucent to allow microscopic analysis ill situ. These requirements were met by glassy, translucent, highly cross linked polymer networks formed by copolymerization of trimethylolpropane triacrylate (TMPTA) copolymerized with poly(ethylene glycol) diacrylate (PEGDA).
The PEG-based surface of these films was electro neutral and had a low interface energy with water. The hydrated high-molecular PEG chains at the water interface likely exhibited high segmental mobility and thus were thought to render the surface highly protein-repellent and cell non-adhesive.14H43 Other important qualities of this substrate material consisted in its mechanical strength. Small amount of swelling in both organic solvents and water (as a result of the high degree of cross linking), and the films’ optical properties:
Since the films were completely translucent, light microscopy of ceil cultures on the films was possible. Modification of the Poly (Ethylene Glycol)-Containing Substrate Material
When the original protocol based on TMPT A and PEGDA, as reported by DrumheIIer and Hubbell, 1994,139 gave rise in my hands to films of insufficient cell adhesion resistance.
further experiments indicated that only films made with poly(ethylene glycol) a-monoacrylate co-monomethyl ether (PEGMA, Figure 3.1) exhibited similar resistance to cell adhesion as previously reported by Drumheller and Hubbell.139 These results suggest that the degree of acrylation in what Drumheller and Hubbell believed to be poly(ethylene glycol) diacrylate might actually have been significantly lower, such that fraction of the polymer used had actually been poly(ethylene glycol) monoacrylate, giving rise to the observed resistance to cell adhesion of the films.
- Photo patterning
Very convenient choices of bifunctional photocrosslinkers for the immobilization of bimolecular on polymeric surfaces are benzophenones and certain arylazides, some of which can be UV photo activated at wavelengths above 320 nm.
Biological activities of photo-immobilized biomolecules are, in general, not affected by the conditions used for light activation. 144·43 Inspired by the work of Huebsch et aI., 1996,145 the photocrosslinker N-succinimidyl-6-[4’azido-2′-nitrophenylaminolhexanoate (SANPAH) (Figure 3.4), which forms a reactive nitrene upon irradiation, seemed particularly convenient for the functionalization of the substrate films.
SANPAH can easily be radio labeled with 12’1 for future experiments to determine the surface concentrations of 12’I-SANPAH-immobilized peptides on substrate surfaces.
- MATERIALS AND METHODS
Synthesis of poly(ethylene-glycol) <x-monoacrylate ro-monomethylether
Poly(ethylene glycol) a-monoacrylate ro-monomethylether (PEGMA), mol. wt. 5000, was prepared from PEG monomethylether, mol. wt. 5,000 (Fluka, Switzerland, Mil ca. 5000 according to supplier). PEG was dried by isotropic distillation in benzene for I hr using a distillation column.
After cooling to less than 50°C under argon, triethylamine (2.2 eg., Aldrich) was added. Addition of acryloyl chloride in two half-portions (4.0 eg. total, Aldrich) separated by 10 min initiated the reaction. The reaction continued with stirring overnight in the dark at room temperature under argon. The resulting pale yellow solution was filtered and the reaction product precipitated by drop wise addition of the solution to diethyl ether in an ice bath.
After recovery by filtration, the precipitate was washed with diethyl ether and dried in vacuum. lH NMR spectrometry in DCCI, resulted in the following characteristic peaks: 3.6 ppm (94.38 H, PEG), 4.3 ppm (t, 1.93 H, -CH2-CH2-O-CO-CH=CH2), 5.8 ppm (dd, 1.00 H, CH:=CH-COO-), 6.1 ppm, 6.4 ppm (dd, 2.08 H, CH2=CH-COO-).
- Photo initiated Formation of Highly Crosslinked Networks
As explained above, the adhesion-resistant substrate material for this study were films of a highly crosslinked network of trimethylolpropane triacrylate (TMPT A, Aldrich) and pentaerythritol tetraacrylate (PETA, Aldrich) copolymerized with PEGMA (Figure 3.1) in the presence of photoinitiator benzil dimethyl ketal (BDMK, Aldrich),
Which was based on earlier materials by Drumheller and Hubbe11.139.141 Briefly, 0.8 g PEGMA were dissolved in 1.8 mL TMPTA and 0.2 mL PETA by heating the mixture to 100°C. After addition of 26 f-lL BDMK solution (300 mg/mL in TMPT A). the homogeneous mixture was filled into a circular space formed by a PTFE gasket (I-mm thickness, ~14-mm diameter; Small Parts) clamped between two clean glass coverslips (Corning). After re-heating to 100°C in a pre-warmed oven with a glass window (Bioblock).
A IOO-W medium-pressure mercury vapor UV light source (Blak-Ray, UVP) was shone through the oven window for I min, thus exposing the coverslip assembly to a flux of 10 mW/cmc perpendicular to the opening in the PTFE gasket. The resulting polymer films were gently removed from the assembly and postcured under UV irradiation for I min.
- Automated Fmoc-based Peptide Synthesis on Solid Supports
Oligopeptides RGDSG, RDGSG. KAF(~A)KLAARLYRKA, GGGYIGSR. GGGIKV A V. and HAV were synthesized on solid polystyrene support with a “Pioneer” peptide synthesizer (Applied Biosystems. USA) by automated solid phase peptide synthesis using 0.4 g peptide amide resin (NovaSyn TGR, Novabiochem-Calbiochem AG.
- Photolabelling of Peptides
Under exclusion of light, peptide resins from different syntheses were separately placed in N,N-dimethyl forrnamide (DMF) containing a two-fold excess of the photolabel SANPAH and activator N-hydroxybenzotrizole (HOBt) per theoretical peptide, based on the protocol by Huebsch et a1.40, 1996. After reacting for 2 h, the resin was recovered by vacuum filtration through fritted glass funnels and washed with 10 resin volumes of DMF, then 5 volumes of MeOH, and dried. Peptides were cleaved from the resin and deprotected for 4 h by shaking the resin in 10 mL of a solution containing 8.8 mL trif\uoroacetic acid (TFA. Fluka, Switzerland), 0.5 mL phenol (Aldrich), 0.2 mL triisopropylsilane (Aldrich), and 0.5 mL water. Precipitation of the orange photolabel1ed peptides occurred when the filtration flow-through was added drop-wise to chil1ed diethyl ether (~40 mL). The deep orange precipitate was recovered by vacuum filtration (0.2 11m pore-sized PTFE membrane filters, Gelman Sciences) and washed with three ~5 mL portions of diethyl ether.
4.
Effect of polyethylene glycol on polysaccharides: From molecular modification, composite matrixes, synergetic properties to embeddable application in food fields
1. Modification of PEG
PEG has wide range of molecular weight (MW) and thus wide-ranged utility in different areas. However, the terminal hydroxyl group of PEG has low reactivity. Upon dissolution in water for a long time, PEG may endure decomposition and may reach complete disintegration at high temperature environment. It is also easily degradable, when it is exposed to microbes (Catauro et al., 2023), finally limiting the applications. Modification matters therefore in enhancing the essential performance of “Polyethylene Glycol”.
2. Broader perspectives of PEG-polysaccharides beyond food applications
PEG/polysaccharides are increasingly adopted as versatile materials, and also have broad applications beyond food fields, mainly including environmental engineering applications, pharmaceutical applications, tissue engineering applications, etc.
PEG-polysaccharides with the strong biocompatibility have considerable potentials in environmental engineering, which could improve the efficiency and reduce the cost of water treatment. PEG-polysaccharide hydrogels are one the most effective adsorptive
3. Embeddable applications of PGE/polysaccharides in food filed
Increasing studies have revealed high food application possibility of “Polyethylene Glycol”/polysaccharides with excellent embeddable characteristics, including promoting food packaging development, improving intelligent indication/detection in food, innovating personalized food-related products, improving bioavailability of specialized food in human (Fig. 5), etc.
4. Enhanced and synergetic properties of PEG/polysaccharides
The functionalization of PEG on polysaccharides could induce to the synergetic properties of PEG, including mechanical properties, antibacterial properties, antioxidant properties, self-healing properties and delivery properties (Fig. 4) (Andrade Del Olmo et al., 2022; Cheng, Huang, Wei, & Hsu, 2019; Mohammadi & Babaei, 2022).
5. Characterization techniques of PEG-polysaccharide systems
In order to research the structure and properties of “Polyethylene Glycol”-polysaccharide systems,various complementary techniques have been employed and investiated. The fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) are common characterization techniques for interaction, crystallinity and structure analysis of PEG-polysaccharide systems. Electron microscopy strategies (scanning electron microscopy, SEM; transmission electron microscopy, TEM; atomic force microscopy, AFM) are often..
6. PEG/polysaccharide matrixes
Polysaccharides, the naturally occurring macromolecular polymers, are widely found in various food sources and possess excellent properties and characteristics for application in food fields, but also possess disadvantages like limited solubility, brittleness, inflexibility, restricted biocompatibility structure, etc. “Polyethylene Glycol”, with the wide range of available end-groups, e.g., hydroxyl, amino, carboxyl, tosylate, aldehyde, azide, biotin, thiol, acid and epoxy, could functionalize polysaccharides..
7. Modification of PEG
PEG has wide range of molecular weight (MW) and thus wide-ranged utility in different areas. However, the terminal hydroxyl group of PEG has low reactivity. Upon dissolution in water for a long time, PEG may endure decomposition and may reach complete disintegration at high temperature environment. It is also easily degradable, when it is exposed to microbes (Catauro et al., 2023), finally limiting the applications. Modification matters therefore in enhancing the essential performance of “Polyethylene Glycol”
Conclusion
PEGs with wide-ranged MW had characteristics such as biocompatibility, inert nature, solubility, flexibility and adjustable hydrophobicity & hydrophilicity. Molecular modification with amino group, carboxyl groups, aldehyde groups, tosylate groups, long chains-grafting/polymerization/crosslinking groups, no-covalent interactions, inorganic materials and ionic bonds could contribute to the structural versability of PEG materials. These PEG materials could functionalize polysaccharides including..
1. Where can you find ethylene glycol?
The price of Ethylene Glycol (United States) increased during November 2019 to 569 USD per metric ton, which represents a slight rise of 3% compared to the previous month’s value.
2. How much does ethylene glycol cost?
The price of Ethylene Glycol (United States) increased during November 2019 to 569 USD per metric ton, which represents a slight rise of 3% compared to the previous month’s value.
3. Why is polyethylene glycol so expensive?
The rising freight rates from China to North America and North Europe to North America further elevated production costs, pushing prices higher. Therefore, these factors collectively created a challenging environment for polyethylene glycol ( “Polyethylene Glycol”) pricing in North America
4. Is ethylene glycol still used?
Ethylene glycol has many uses, including as antifreeze in cooling and heating systems, in hydraulic brake fluids, and as a solvent
- Is ethylene glycol good or bad?
Ethylene glycol exposure can be extremely dangerous, with significant morbidity and mortality if left untreated. Ethylene glycol is a colorless, sweet-tasting liquid commonly found in antifreeze but occasionally used for other purposes, such as industrial solvents.26-Sept-2022.