Polyethylene Glycol: the fully customizable compound

Polyethylene glycol, or PEG for short, is a highly customizable polymer. It can be manipulated into so many different shapes, sizes, and functional derivatives that it’s no wonder we see it everywhere. In this article, we’ll take a look at some of the key properties of polyethylene glycol to understand why it’s so useful in so many applications.

Polyethylene glycol in all its forms
Is it a liquid or a solid? Is it hydrophilic or hydrophobic? Actually, it’s whatever you want it to be! But knowing what you want is critical to choosing the right type of PEG for your application.
Polyethylene glycol consists of repeating units of ethylene glycol, [-(CH2CH2O)n]. The number of repeating units will vary, so it can have multiple different molecular weights. The molecular weight is important, because this will contribute to the key properties of the substance.

PEG has a couple of different nomenclature systems. The number following the abbreviation denotes the average number of repeating ethylene glycol units (e.g., PEG-4) OR the approximate molecular weight (e.g., PEG-200).

Low molecular weight PEG has very distinct properties from high molecular weight PEG. From about 100 to 600 or 700 g/mol, PEG is a liquid at room temperature, with a syrupy consistency. As it gets heavier, it morphs into a soft solid, finally developing a hard, crystalline structure at over 2000 g/mol. If you check out the product page for PEG on Lab Alley, you will notice that there is a range of different molecular weights, with some sold as a liquid, and others in granules.

Side note, don’t be confused by the term polyethylene oxide, or PEO. It’s actually the same as PEG, but typically refers to molecular weights of over 100,000.

Here are some examples of how the molecular weight determines the application of PEG:

The molecular weight determines the metabolism of PEG in the body. This is important to understand, because as we’ll see in the next section, PEG has wide usage in drug delivery systems.

Furthermore, there are many different derivatives of PEG. That is, it can have different functional groups attached to it. For example, instead of the non-derivatized PEG, which has a hydroxyl group at the end of the ethylene glycol chain, there could be a thiol, an aldehyde, or an amine, all of which exhibit different chemistry. This changes the reactivity of the polymer, and therefore the functionality.

The chemistry of PEG makes it an excellent solubilizing agent. It can effectively bridge the gap between hydrophilic and hydrophobic substances. This makes it a useful emulsifier, especially as a food additive. It has excellent water-holding capacity, so it can be used to form hydrogels. These characteristics make it ideal for drug delivery systems.

Safety Profile
The non-toxicity of PEG is the prerequisite for almost all of its applications. It’s also what makes it so difficult a polymer to replace – while other synthetic polymers may deliver the same functionality, they may not necessarily be biological inert.

PEG is special because it does not typically illicit an immune response from the body. Generally speaking, PEG is biologically inert. It does not significantly adsorb to proteins, or get taken up by cells, and it causes a negligible degree of inflammation.

Higher molecular weight PEG is more inert. That is, the gastrointestinal and dermal absorption decrease as PEG gets heavier. Acceptable intake is considered to be up to 10 mg/kg bodyweight, daily. Beyond this dosage could begin to cause toxicity and an immune response, but these side effects are extremely rare.

Polyethylene glycol in action
To wrap up, let’s take a quick look at a few real examples of how PEG might be used clinically, specifically in drug delivery systems.
1. Cancer therapy. A recent review covered the uses of PEG-based hydrogels for drug delivery systems in cancer therapy. The reviewers note that PEG is ideal due to its low cellular toxicity, excellent stability in circulation, and its versatility.
2. Bone regeneration. A 2023 paper looked at the use of PEG hydrogels for drug delivery systems that promote bone regeneration. The authors note that PEG is ideal because it is highly biocompatible and has good hydrophilicity.
3. Skin regeneration. A 2022 paper reviewed the use of PEG to deliver skin sprays to promote wound healing and skin regeneration. The use of PEG in a spray enables drug deliver of wounds of large surface area.

Although PEG is a synthetic molecule, it is readily accepted by the body. It is easy to manipulate its size and functional groups, depending on the application in mind. Thanks to its high adaptability and low toxicity, PEG has been established as a critically important polymer, especially in food and drug delivery systems.

References
Anisha A. D’souza & Ranjita Shegokar (2016) Polyethylene glycol (PEG): a versatile polymer for pharmaceutical applications, Expert Opinion on Drug Delivery, 13:9, 1257-1275, DOI: 10.1080/17425247.2016.1182485 

H.W. Leung, Polyethylene Glycol, Editor(s): Philip Wexler, Encyclopedia of Toxicology (Third Edition), Academic Press, 2014, Pages 1043-1044, ISBN 9780123864550, https://doi.org/10.1016/B978-0-12-386454-3.00050-6. 

Pleguezuelos-Beltrán, Paula et al. “Advances in spray products for skin regeneration.” Bioactive materials vol. 16 187-203. 8 Mar. 2022, doi:10.1016/j.bioactmat.2022.02.023

Sun, Shouye et al. “Drug delivery systems based on polyethylene glycol hydrogels for enhanced bone regeneration.” Frontiers in bioengineering and biotechnology vol. 11 1117647. 30 Jan. 2023, doi:10.3389/fbioe.2023.1117647

Wang Z, Ye Q, Yu S, Akhavan B. Poly Ethylene Glycol (PEG)-Based Hydrogels for Drug Delivery in Cancer Therapy: A Comprehensive Review. Advanced Healthcare Materials. 2023 Jul;12(18):e2300105. DOI: 10.1002/adhm.202300105. PMID: 37052256.