Polyethylene glycol (PEG;/ˌpɒliˈɛθəlˌiːnˈɡlaɪˌkɒl,-ˈɛθɪl-,-ˌkɔːl/) is apolyether compound derived frompetroleum with many applications, from industrial manufacturing tomedicine. PEG is also known aspolyethylene oxide (PEO) orpolyoxyethylene (POE), depending on itsmolecular weight. The structure of PEG is commonly expressed as H−(O−CH2−CH2)n−OH.[3]
PEG is commonly incorporated into hydrogels which present a functional form for further use.[4]
Pharmaceutical-grade PEG is used as anexcipient in many pharmaceutical products, in oral, topical, and parenteral dosage forms.[5]
PEG is the basis of a number oflaxatives (asMiraLax, RestoraLAX, MoviPrep, etc.).[6]Whole bowel irrigation with polyethylene glycol and addedelectrolytes is used for bowel preparation beforesurgery orcolonoscopy or for children with constipation.[7]Macrogol (with brand names such as Laxido, Movicol and Miralax) is the generic name for polyethylene glycol used as a laxative. The name may be followed by a number that represents the average molecular weight (e.g. macrogol 3350, macrogol 4000, or macrogol 6000).
An example of PEGhydrogels (seeBiological uses section) in a therapeutic has been theorized by Ma et al. They propose using the hydrogel to addressperiodontitis (gum disease) by encapsulatingstem cells in the gel that promote healing in the gums.[8] The gel with encapsulated stem cells was to be injected into the site of disease and crosslinked to create the microenvironment required for the stem cells to function.
APEGylated lipid is used as an excipient in both theModerna andPfizer–BioNTech vaccines forSARS-CoV-2. BothRNA vaccines consist ofmessenger RNA, or mRNA, encased in a bubble of oily molecules calledlipids. Proprietary lipid technology is used for each. In both vaccines, the bubbles are coated with a stabilizing molecule of polyethylene glycol.[10] PEG could trigger allergic reaction,[11] and allergic reactions are the driver for both the United Kingdom and Canadian regulators to issue an advisory, noting that: two "individuals in the U.K. ... were treated and have recovered" fromanaphylactic shock.[12][13] The US CDC stated that in their jurisdiction six cases of "severe allergic reaction" had been recorded from more than 250,000 vaccinations, and of those six only one person had a "history of vaccination reactions".[14]
The remains of the 16th centurycarrackMary Rose undergoing conservation treatment with PEG in the 1980sTerra cotta warrior, showing traces of original color
Polyethylene glycol can serve as a green reaction medium in a variety of organic reactions.[15]
PEG is frequently used topreserve waterlogged wood and other organic artifacts that have been salvaged from underwater archaeological contexts, as was the case with the warshipVasa in Stockholm,[16] and similar cases. It replaces water in wooden objects, making the wood dimensionally stable and preventing the warping or shrinking of the wood when it dries.[6] In addition, PEG is used when working withgreen wood as a stabilizer, and to prevent shrinkage.[17]
PEG has been used to preserve the painted colors onTerracotta Warriors unearthed at a UNESCO World Heritage site in China.[18] These painted artifacts were created during theQin Shi Huang (first emperor of China) era. Within 15 seconds of the terra-cotta pieces being unearthed during excavations, the lacquer beneath the paint begins to curl after being exposed to the dryXi'an air. The paint would subsequently flake off in about four minutes. The German Bavarian State Conservation Office developed a PEG preservative that when immediately applied to unearthed artifacts has aided in preserving the colors painted on the pieces of clay soldiers.[19]
PEG is often used (as an internal calibration compound) inmass spectrometry experiments, with its characteristic fragmentation pattern allowing accurate and reproducible tuning.
An example study was done using PEG-diacrylate hydrogels to recreate vascular environments with the encapsulation ofendothelial cells andmacrophages. This model furthered vascular disease modeling and isolated macrophage phenotype's effect on blood vessels.[23]
PEG is commonly used as a crowding agent inin vitro assays to mimic highly crowded cellular conditions.[24] Although polyethylene glycol is considered biologically inert, it can formnon-covalent complexes with monovalentcations such asNa+,K+, Rb+, and Cs+, affectingequilibrium constants of biochemical reactions.[25][26]
Inmicrobiology, PEG precipitation is used to concentrate viruses. PEG is also used to induce complete fusion (mixing of both inner and outer leaflets) in liposomes reconstitutedin vitro.
Gene therapy vectors (such as viruses) can be PEG-coated to shield them from inactivation by the immune system and to de-target them from organs where they may build up and have a toxic effect.[27] The size of the PEG polymer is important, with larger polymers achieving the best immune protection.
When working withphenol in a laboratory situation,PEG 300 can be used on phenol skin burns to deactivate any residual phenol.[31]
Inbiophysics, polyethylene glycols are the molecules of choice for the functioning ion channel diameter studies, because in aqueous solutions they have a spherical shape and can block ion channel conductance.[32][33]
PEG is used in a number oftoothpastes[6] as adispersant. In this application, it binds water and helps keepxanthan gum uniformly distributed throughout the toothpaste.
PEG has been used as the gate insulator in an electric double-layer transistor to induce superconductivity in an insulator.[39]
PEG is used as a polymer host for solid polymer electrolytes. Although not yet in commercial production, many groups around the globe are engaged in research on solid polymer electrolytes involving PEG, to improve their properties, and in permitting their use in batteries, electro-chromic display systems, and other products in the future.
PEG is injected into industrial processes to reduce foaming in separation equipment.
PEG was used as an additive to silver halide photographicemulsions.
PEG is used as an active ingredient in agricultural soil wetter, which improves water-retention and seedling growth.[41]
PEGs and PEG–based polymers are also common constituents of agricultural formulations, where they serve as additives that enhance the stability and application efficiency of active ingredients such as pesticides and fertilizers. An inventory of formulation additives used in Germany and Switzerland identified PEG-based (co)polymers as the most frequently occurring class of water-soluble polymers in these products, accounting for roughly half of all identified polymers by trade name.[42]
Binary polyethylene oxide and titania solid-state redox electrolytes are used today for efficient nanocrystalline TiO2 photoelectrochemical cells.[43]
Polyethylene oxides (PEO's) have "very low single dose oral toxicity", on the order of tens ofgrams perkilogram of human body weight when ingested by mouth.[3] Because of its low toxicity, PEO is used in a variety of edible products.[44] It is also used as alubricating coating for various surfaces inaqueous and non-aqueous applications.[45]
A 2015 study appears to challenge the FDA's conclusion. In the study, a high-sensitivityELISA assay detected anti-PEGantibodies in 72% of randomblood plasma samples collected from 1990 to 1999. According to the study's authors, this result suggests that anti-PEG antibodies may be present, typically at low levels, in people who were never treated withPEGylated drugs.[49][50] Due to its ubiquity in many products and the large percentage of the population with antibodies to PEG, which indicates anallergic reaction, hypersensitive reactions to PEG are an increasing health concern.[51][52] Allergy to PEG is usually discovered after a person has been diagnosed with an allergy to several seemingly unrelated products—including processed foods, cosmetics, drugs, and other substances—that contain or were manufactured with PEG.[51]
PEG,PEO, andPOE refer to anoligomer or polymer ofethylene oxide. The three names are chemically synonymous, but historicallyPEG is preferred in the biomedical field, whereasPEO is more prevalent in the field of polymer chemistry. Because different applications require different polymer chain lengths,PEG has tended to refer to oligomers and polymers with a molecular mass below 20,000g/mol,PEO to polymers with a molecular mass above 20,000g/mol, andPOE to a polymer of any molecular mass.[53] PEGs are prepared bypolymerization of ethylene oxide and are commercially available over a wide range of molecular weights from 300g/mol to 10,000,000g/mol.[54]
PEG and PEO are liquids or low-melting solids, depending on theirmolecular weights. While PEG and PEO with different molecular weights find use in different applications and have different physical properties (e.g.viscosity) due to chain length effects, their chemical properties are nearly identical. Different forms of PEG are also available, depending on theinitiator used for the polymerization process – the most common initiator is a monofunctional methyl ether PEG, or methoxypoly(ethylene glycol), abbreviated mPEG. Lower-molecular-weight PEGs are also available as purer oligomers, referred to as monodisperse, uniform, or discrete. Very high-purity PEG has recently been shown to be crystalline, allowing the determination of a crystal structure byx-ray crystallography.[54] Since purification and separation of pure oligomers is difficult, the price for this type of quality is often 10–1000 fold that of polydisperse PEG.
PEGs are also available with different geometries.
Branched PEGs have three to ten PEG chains emanating from a central core group.
Star PEGs have 10 to 100 PEG chains emanating from a central core group.
Comb PEGs have multiple PEG chains normally grafted onto a polymer backbone.
The numbers that are often included in the names of PEGs indicate their average molecular weights (e.g. a PEG withn = 9 would have an average molecular weight of approximately 400daltons, and would be labeledPEG 400). Most PEGs include molecules with a distribution of molecular weights (i.e. they are polydisperse). The size distribution can be characterized statistically by itsweight average molecular weight (Mw) and itsnumber average molecular weight (Mn), the ratio of which is called thepolydispersity index (ĐM).Mw andMn can be measured bymass spectrometry.
PEG and related polymers (PEG phospholipid constructs) are oftensonicated when used in biomedical applications. However, as reported by Murali et al., PEG is very sensitive to sonolytic degradation and PEG degradation products can be toxic to mammalian cells. It is, thus, imperative to assess potential PEG degradation to ensure that the final material does not contain undocumented contaminants that can introduce artifacts into experimental results.[56]
PEGs and methoxypolyethylene glycols are manufactured byDow Chemical under the trade nameCarbowax for industrial use, andCarbowax Sentry for food and pharmaceutical use. They vary in consistency from liquid to solid, depending on the molecular weight, as indicated by a number following the name. They are used commercially in numerous applications, including foods,cosmetics, pharmaceutics,biomedicine, dispersing agents, solvents,ointments,suppository bases, as tabletexcipients, and aslaxatives. Some specific groups arelauromacrogols,nonoxynols,octoxynols, andpoloxamers.
The production of polyethylene glycol was first reported in 1859. BothA. V. Lourenço andCharles Adolphe Wurtz independently isolated products that were polyethylene glycols.[57] Polyethylene glycol is produced by the interaction ofethylene oxide with water,ethylene glycol, or ethylene glycol oligomers.[58] The reaction is catalyzed by acidic or basic catalysts. Ethylene glycol and its oligomers are preferable as a starting material instead of water because they allow the creation of polymers with a lowpolydispersity (narrow molecular weight distribution). Polymer chain length depends on the ratio of reactants.
HOCH2CH2OH + n(CH2CH2O) → HO(CH2CH2O)n+1H
Depending on the catalyst type, the mechanism ofpolymerization can be cationic or anionic. The anionic mechanism is preferable because it allows one to obtain PEG with a low polydispersity. Polymerization of ethylene oxide is an exothermic process. Overheating or contaminating ethylene oxide with catalysts, such as alkalis or metal oxides, can lead to runaway polymerization, which can end in an explosion after a few hours.
Polyethylene oxide, or high-molecular-weight polyethylene glycol, is synthesized bysuspension polymerization. It is necessary to hold the growing polymer chain insolution in the course of thepolycondensation process. The reaction is catalyzed by magnesium-, aluminium-, or calcium-organoelement compounds. To preventcoagulation of polymer chains from solution, chelating additives, such asdimethylglyoxime, are used.
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^Firouzabadi H, Iranpoor N, Gholinejad M (January 2010). "One-Pot Thioetherification of Aryl Halides Using Thiourea and Alkyl Bromides Catalyzed by Copper(I) Iodide Free from Foul-Smelling Thiols in Wet Polyethylene Glycol (PEG 200)".Advanced Synthesis & Catalysis.352 (18):119–24.doi:10.1002/adsc.200900671.
^Breton MF, Discala F, Bacri L, Foster D, Pelta J, Oukhaled A (3 July 2013). "Exploration of Neutral Versus Polyelectrolyte Behavior of Poly(ethylene glycol)s in Alkali Ion Solutions using Single-Nanopore Recording".The Journal of Physical Chemistry Letters.4 (13):2202–2208.doi:10.1021/jz400938q.ISSN1948-7185.
^Harmening DM (2005).Modern Blood Banking & Transfusion Practices. F. A. Davis Company.ISBN978-0-8036-1248-8.
^Monteiro-Riviere NA, Inman AO, Jackson H, Dunn B, Dimond S (May 2001). "Efficacy of topical phenol decontamination strategies on severity of acute phenol chemical burns and dermal absorption: in vitro and in vivo studies in pig skin".Toxicology and Industrial Health.17 (4):95–104.Bibcode:2001ToxIH..17...95M.doi:10.1191/0748233701th095oa.PMID12479505.S2CID46229131.
^Ueno K, Nakamura S, Shimotani H, Ohtomo A, Kimura N, Nojima T, et al. (November 2008). "Electric-field-induced superconductivity in an insulator".Nature Materials.7 (11):855–8.Bibcode:2008NatMa...7..855U.doi:10.1038/nmat2298.PMID18849974.
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^abWenande E, Garvey LH (July 2016). "Immediate-type hypersensitivity to polyethylene glycols: a review".Clinical and Experimental Allergy.46 (7):907–22.doi:10.1111/cea.12760.PMID27196817.S2CID1247758.
^For example, in theonline catalogArchived 29 December 2006 at theWayback Machine of Scientific Polymer Products, Inc., poly(ethylene glycol) molecular weights run up to about 20,000, while those of poly(ethylene oxide) have six or seven digits.
