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[Home](https://www.sigmaaldrich.com/US/en)[Drug Delivery](https://www.sigmaaldrich.com/US/en/applications/materials-science-and-engineering/drug-delivery)Polyethylene Glycol (PEG) Selection Guide
# Polyethylene Glycol (PEG) Selection Guide
### Read more about
- [What is Polyethylene Glycol](https://www.sigmaaldrich.com#what-is-polyethylene-glycol)
- [Featured Peg Products](https://www.sigmaaldrich.com#featured-peg-products)
- [How is Polyethylene Glycol Used?](https://www.sigmaaldrich.com#how-is-polyethylene-glycol-used)
- [Find the Right PEG for Your Research Application](https://www.sigmaaldrich.com#find-the-right-peg)
- [References](https://www.sigmaaldrich.com#references)
 Selection Guide")
__Poly(ethylene glycol) (PEG) structure__
## [](https://www.sigmaaldrich.com)What is Polyethylene Glycol?
Poly(ethylene glycol) (PEG) is a synthetic, hydrophilic, biocompatible polymer with widespread use in biomedical and other applications. PEGs are synthesized using a ring-opening polymerization of ethylene oxide to produce a broad range of molecular weights and molecular weight distributions (polydispersity); however, discrete PEGs ([dPEG® reagents](https://www.sigmaaldrich.com/US/en/search/polyethylene-glycol-dpeg%C2%AE?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol%20dPEG%C2%AE&type=product)) are synthesized with a single, specific molecular weight. PEGs can be synthesized in linear, branched, Y-shaped, or multi-arm geometries. PEGs can be activated by the replacement of the terminal hydroxyl end group with a variety of reactive functional end groups enabling crosslinking and conjugation chemistries.
## Featured PEG Products
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## [](https://www.sigmaaldrich.com)How is Polyethylene Glycol used?
PEGs are non-toxic, FDA-approved, generally nonimmunogenic, and are frequently used in many biomedical applications including bioconjugation,1 drug delivery,2,3 surface functionalization,4 and tissue engineering.5 Bioconjugation with PEG (also known as PEGylation) is the covalent conjugation of drug targets such as peptides, proteins, or oligonucleotides with PEG for the optimization of pharmacokinetic properties.6 In drug delivery, PEGs can be used as linkers for antibody-drug conjugates (ADCs)7 or as a surface coating on nanoparticles to improve systemic drug delivery.6 PEG [hydrogels](https://www.sigmaaldrich.com/US/en/technical-documents/technical-article/materials-science-and-engineering/tissue-engineering/degradable-polyethylene-glycol-hydrogels) are water-swollen, three-dimensional, polymer networks resistant to protein adhesion and biodegradation.8 PEG hydrogels are produced by crosslinking reactive PEG end groups and are commonly used in tissue engineering and drug delivery.
## [](https://www.sigmaaldrich.com)Find the right PEG for Your Research Application
Four general characteristics are considered when selecting PEGs for bioconjugation, drug delivery and tissue engineering research applications:
__Functionality__
- [Monofunctional PEGs](https://www.sigmaaldrich.com/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product) contain a single chemically-reactive end and are used for PEGylation, surface conjugation, and nanoparticle coating.
- PEGs containing two reactive ends, which can either have the same ([homobifunctional PEG](https://www.sigmaaldrich.com/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product)) or different ([heterobifunctional PEG](https://www.sigmaaldrich.com/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product)) reactive groups are useful for conjugation and crosslinking for hydrogels
__Polymer Architecture__
- [Linear PEGs](https://www.sigmaaldrich.com/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product) are commonly used for PEGylation, bioconjugation, and crosslinking
- Multi-arm PEGs ([4-](https://www.sigmaaldrich.com/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product),6-,[8-](https://www.sigmaaldrich.com/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product)arm) can be crosslinked into hydrogels and scaffolds for drug delivery or tissue engineering
- [Y-shaped PEGs](https://www.sigmaaldrich.com/search/y-shaped-pegs?focus=products&page=1&sort=relevance&term=Y-shaped%20pegs&type=product) are typically used for PEGylation, as the branched structure may improve stability *in vivo.*
__Reactivity__
- Covalent conjugation: PEGs with reactive end groups, such as an N-hydroxysuccinimide ester, thiol, or carboxyl group, can be covalently conjugated to corresponding functional groups. The conjugation chemistry chosen determines site of attachment and number of PEGs per molecule.
- [Click chemistry](https://www.sigmaaldrich.com/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product) requires PEGs with azide or alkyne reactive groups. Click chemistry is a rapid, selective, and bioorthogonal method for conjugation or hydrogel formation.
- Polymerization and photopolymerization can be achieved rapidly using acrylate-terminated PEGs under mild reactive conditions
__Molecular Weight__
- Bioconjugation: PEGs with molecular weights ≥5 kDa are typically used for conjugation to small molecules, siRNA, and peptides. Low molecular weight PEGs (≤5 kDa) are often used for PEGylation of proteins.
- Surface conjugation and crosslinking can be completed with PEGs that are < 40 kDa
- Hydrogel formation: PEG molecular weight will influence the hydrogel mesh size and mechanical properties. Typically, PEGs ≥5 kDa molecular weight are used.
### Common functional groups and their corresponding reactive groups are listed in the table below.
__Functional Groups____Reactive Groups__
[Primary Amine](https://www.sigmaaldrich.com/US/en/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product) (–NH2)[NHS⧧ Ester](https://www.sigmaaldrich.com/US/en/search/polyethylene-glycol-nhs?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol%20NHS&type=product)
Aldehyde
Anhydride
EpoxideIsocyanate
Sulfonyl Chloride
Fluorobenzene
Imidoester[Carbodiimide](https://www.sigmaaldrich.com/US/en/search/carbodiimide-peg?focus=products&page=1&perpage=30&sort=relevance&term=carbodiimide%20peg&type=product)
Acyl Azide
Carbonate
Fluorophenyl Ester
[Thiol](https://www.sigmaaldrich.com/US/en/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product) (–SH)[Maleimide](https://www.sigmaaldrich.com/US/en/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product)
[Pyridyl disulfide](https://www.sigmaaldrich.com/US/en/search/peg-pyridyl-disulfide?focus=products&page=1&sort=relevance&term=PEG%20Pyridyl%20disulfide&type=product)Haloacetyl
[Vinylsulfone](https://www.sigmaaldrich.com/US/en/search/polyethylene-glycol-vinylsulfone?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol%20Vinylsulfone&type=product)Iodoacetyl
[Carboxyl](https://www.sigmaaldrich.com/US/en/search/polyethylene-glycol?focus=products&page=1&sort=relevance&term=Polyethylene%20Glycol&type=product) (–COOH)Amines
Carbonyl (–CHO)[Hydrazides](https://www.sigmaaldrich.com/US/en/search/mpeg-hydrazide?focus=products&page=1&sort=relevance&term=mPEG-Hydrazide&type=product)Alkoxyamines
⧧N-Hydroxysuccinimide
⤒1-Ethyl-3-\[3-dimethylaminopropyl]carbodiimide hydrochloride)
⤓Dicyclohexylcarbodiimide
### References
1\.
Hermanson GT. 2013. Bioconjugate Techniques,. Burlington, Elsevier Science.
2\.
Translating Polymer Science for Drug Delivery; PDDT. 2015. Translating Polymer Science for Drug Delivery; . Aldrich Materials Science: Milwaukee, WI,.
3\.
Parveen S, Sahoo SK. 2011. Long circulating chitosan/PEG blended PLGA nanoparticle for tumor drug delivery. European Journal of Pharmacology. 670(2-3):372-383. [https://doi.org/10.1016/j.ejphar.2011.09.023](https://doi.org/10.1016/j.ejphar.2011.09.023)
4\.
Manson J, Kumar D, Meenan BJ, Dixon D. 2011. Erratum to: Polyethylene glycol functionalized gold nanoparticles: the influence of capping density on stability in various media. Gold Bull. 44(3):195-196. [https://doi.org/10.1007/s13404-011-0023-8](https://doi.org/10.1007/s13404-011-0023-8)
5\.
Fairbanks BD, Schwartz MP, Bowman CN, Anseth KS. 2009. Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: polymerization rate and cytocompatibility. Biomaterials. 30(35):6702-6707. [https://doi.org/10.1016/j.biomaterials.2009.08.055](https://doi.org/10.1016/j.biomaterials.2009.08.055)
6\.
Suk JS, Xu Q, Kim N, Hanes J, Ensign LM. 2016. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery. Advanced Drug Delivery Reviews. 9928-51. [https://doi.org/10.1016/j.addr.2015.09.012](https://doi.org/10.1016/j.addr.2015.09.012)
7\.
Jain N, Smith SW, Ghone S, Tomczuk B. 2015. Current ADC Linker Chemistry. Pharm Res. 32(11):3526-3540. [https://doi.org/10.1007/s11095-015-1657-7](https://doi.org/10.1007/s11095-015-1657-7)
8\.
Hoffman AS. 2002. Adv. Drug Deliv. Rev.. 54(1), 3-12.
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