Introduction of Polyethylene Glycol (PEG)

Polyethylene glycol (PEG), a compound composed of repeated ethylene glycol units [-(CH2CH2O)n], is also known as Macrogols. PEG and PEG derivatives have the characteristics of non-irritation, good water solubility, good compatibility, etc. At the same time, they possess excellent lubricity, moisture retention and dispersibility so that they can be used as adhesives, antistatic agents and softeners, and widely applied in cosmetics, pharmaceuticals, chemical fibers, rubber, plastics, paper, paint, electroplating, pesticides, metal processing and food processing industries.

What is PEG?

PEG, a polyether backbone polymer, is synthesized by ring opening polymerization of ethylene oxide using in common cases or usually methanol or water as an initiator. The reaction gives products with one or two end chain hydroxyl groups termed monomethoxy-PEG (mPEG-OH) or diol-PEG (HO-PEG-OH), respectively (Fig. 1).

Mechanism-of-anionic-polymerization-for-PEG-preparationFig. 1. Common PEG chemical structures (Regen. Eng. Transl. Med. 2022, 8: 32-42).

The lone hydroxyl group in the case of the methoxy form, or the two in the case of PEG diol, can be modified to be reactive towards different chemical groups by several activation strategies. Nowadays, a number of activated PEGs are commercially available. These derivatives are commonly monofunctional, either in their linear or branched structure. The chemical structures of several key PEG derivatives are shown in Fig 1. These derivatives are mainly known by their Mw.

Polyethylene Glycol Polymerization

PEG can be synthesized via anionic polymerization of ethylene oxide and any hydroxyl initiators. Hydroxyl group could be from water or ethylene glycol or any diols. They can also be derived from epoxyethane by ring-opening polymerization. Usually, the polymerization process produces a family of PEG molecules with wide Gaussian's distribution of molecular weights. PEG bears only two functional groups limiting the scope for further derivatization with other residues or targeting ligands. Therefore, commercial PEGs are available with different degrees of polymerization and activated functional groups.

Mechanism of anionic polymerization for PEG preparation.Fig. 2. Mechanism of anionic polymerization for PEG preparation.

PEG Chemistry

BOC Sciences is a leading provider of high-quality PEG synthesis services, offering a range of PEG synthesis services to meet the diverse needs of our customers. Customers can work with BOC Sciences' team of experienced chemists to design and synthesize PEG polymers with specific molecular weights, functional groups and other properties to meet their unique needs. Whether it is a simple PEGylation reaction or a more complex polyethylene glycol modification, BOC Sciences can provide customized solutions based on each customer's needs.

PEG Chemical Structure

The structure of PEG can vary depending on molecular weight and degree of polymerization. PEGs have a wide range of molecular weights, from a few hundred Daltons to several thousand Daltons. The molecular weight of PEG determines its physical properties such as viscosity, solubility and biocompatibility. One of the main characteristics of PEG is its hydrophilicity, which makes it highly soluble in water and other polar solvents. This property allows PEG to be easily incorporated into a variety of formulations, such as pharmaceuticals, cosmetics, and personal care products. PEG is also known for its biocompatibility and low toxicity, making it a popular choice for drug delivery systems, tissue engineering, and medical devices.

The chemical structure of PEG can be modified to suit the properties of a specific application by functionalizing end groups or introducing side chains. For example, PEG can be modified with reactive groups such as amines or carboxylic acids to enable conjugation with drugs or targeting ligands for targeted drug delivery. Additionally, PEG can be cross-linked to form hydrogels for tissue engineering or drug release applications.

Solubility of Polyethylene Glycol

PEG earns its fame because of its high structure flexibility, biocompatibility, amphiphilicity, devoid of any steric hindrances, and high hydration capacity. PEG is soluble in water, ethanol and many other organic solvents, like DMF, dichloromethane, toluene, acetonitrile, acrylonitrile, etc. It shows little toxicity and can be eliminated from the body intact by either the kidneys (for PEGs < 30 kDa) or in the faeces (for PEGs > 20 kDa). Other than that, PEG is also non-irritating and stable to heat, acid and alkali, thus it can be widely used in various pharmaceutical applications.

PEG series products have different properties depending on the different molecular weights (Mw). From the perspective of appearance, PEG with Mw of 200-700 are normally liquid at room temperature, and those with Mw > 700 will gradually change from semi-solid to soft solids (Mw between 1000~2000), and finally to hard crystalline solids (Mw > 2000). On the other hand, as the Mw increases, the water solubility, vapor pressure, water absorption, and solubility in organic solvents of PEG will correspondingly decrease, while the freezing point, relative density, flash point and viscosity will increase accordingly. The following table briefly lists several properties of PEG products with different Mw.

PEGylation Technique

PEGylation is defined as the covalent attachment of poly(ethylene glycol) (PEG) chains to bioactive substances, such as nanoparticles, proteins and peptides or non-peptide molecules. This technology emerged gradually with progress in field of biologicals and polymer chemistry and was exploited to improve pharmaceutical applications of a wide range of therapeutics. Nowadays, PEGylation has become the leading approach for overcoming most of the limits of biologics and numbers of FDA approved PEGylated products like enzymes (bovine adenosine deaminase and urate oxidase), cytokines (interferon-α2a, interferon-α2b), granulocyte colony stimulating factors, hormones (epoetin-β), antibodies and their fragments and other organic molecules (pegvisomant, pegatinib) are on the market.

Main advantages of PEGylated proteins Fig. 3. Main advantages of PEGylated proteins (Drug discovery today. 2005, 10(21): 1451-1458).

Tools for PEGylation

CatalogNameCASMolecular WeightMolecular Formula
BPG-2637mPEG24-propionic acid125220-94-2588.68C26H52O14
BPG-2259Hydroxy-PEG8-t-butyl ester1334177-84-2498.60C23H46O11
BPG-1771Hydroxy-PEG2-t-butyl acetate149299-82-1220.26C10H20O5
BPG-1875Amino-PEG3-t-butyl ester252881-74-6277.36C13H27NO5
BPG-2178Biotin-PEG3-propionic acid252881-76-8447.55C19H33N3O7S

Uses of Polyethylene Glycol

Bio-medical Industry

As an amphiphilic polymer, PEG can be soluble in water and most organic solvents, and has the characteristics of good biocompatibility, non-toxicity, and low immunogenicity. It can be excreted through the kidneys, so there will be no accumulation phenomenon in the body. In addition, PEG is easy to bind with proteins, nanocarriers and small molecule drugs, i.e., PEGylation, after the terminal hydroxyl group is activated, thus being widely applied into various biomedical areas, such as drug delivery, imaging diagnosis, pharmaceutical preparation and tissue engineering.

Chemical Synthesis

In recent years PEG aqueous solutions have been widely applied in many different kinds of reaction systems. Their low-toxicity, low volatility, and biodegradability represent important environmentally benign characteristics, which are particularly attractive when combined with their relatively low cost as a bulk commodity chemical. In addition, aqueous PEG solutions may often substitute for other expensive and toxic phase-transfer catalysts.


Polyethylene glycols (PEGs) and their anionic or nonionic derivatives are widely used in cosmetics as surfactants, cleansing agents, emulsifiers, skin conditioners, and humectants, because of their good solubility, viscosity and low toxicity properties. The PEG, their ethers, and their fatty acid esters show little or no ocular or dermal irritation and have extremely low acute and chronic toxicities.

Textile Industry

In the textile industry, PEG can be used as spinning aid, dyeing solvent and dispersant. The solid powder PEG has good properties of film-forming, lubrication and plasticization. It is used to treat fiber additives, which can make fabrics soft, plasticized and refined, and can inhibit the accumulation of static electricity. Above all, PEG can be used as detergent, softener, lubricant, anti-static agent, dispersant, dye carrier, air conditioner and finishing agent in the textile industry.

Plastic Industry

PEG is commonly used as an auxiliary agent in the plastic industry, for example, as a lubricant during extrusion molding, and as a release agent during mold molding. In addition, because of good water solubility, adding PEG into the resins can greatly improve their performance. Substituting PEG for glycerin can improve the toughness of the resin. Adding PEG to the polyurethane resin can improve its strength and elasticity.

Paint Industry

Using PEG as a matrix can replace water-quality emulsified coatings. Low molecular weight PEG has better dispersibility, while high molecular weight PEG can produce better film forming properties. In any cases, coatings with PEG as the matrix show more water-resistant than those with water as the matrix, and can improve the gloss of the film and reduce the odor.


Apart from the application areas mentioned above, PEG also has a wide range of applications in other fields. For example, PEG has a strong binding force with rubber without degrading the rubber. It is often used as a release agent and loosening agent for rubber and polyurethane products. PEG has a dehydrating and fixing effect on tissues. There are also reports on the use of PEG in the preparation and preservation of animal and plant specimens (called plasticized specimens).


  1. Freire, H. et al. Clinical Relevance of Pre-Existing and Treatment-Induced Anti-Poly(Ethylene Glycol) Antibodies. Regen. Eng. Transl. Med. 2022, 8: 32-42.
  2. D'souza, A.A. et al. Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications. Expert Opinion on Drug Delivery. 2016, 13(9): 1257-1275.
  3. Veronese, F.M. et al. PEGylation, successful approach to drug delivery. Drug discovery today. 2005, 10(21): 1451-1458.
  4. Fruijtier-Pölloth, C. Safety assessment on polyethylene glycols (PEGs) and their derivatives as used in cosmetic products. Toxicology. 2005, 214(1-2): 1-38.

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