The DOI matches its Crossref record; 219 of the 219 references it cites were found in a registry or an index.
Poly(ethylene glycol) in Drug Delivery: Pros and Cons as Well as Potential Alternatives
Abstract
Poly(ethylene glycol) (PEG) is the most used polymer and also the gold standard for stealth polymers in the emerging field of polymer‐based drug delivery. The properties that account for the overwhelming use of PEG in biomedical applications are outlined in this Review. The first approved PEGylated products have already been on the market for 20 years. A vast amount of clinical experience has since been gained with this polymer—not only benefits, but possible side effects and complications have also been found. The areas that might need consideration and more intensive and careful examination can be divided into the following categories: hypersensitivity, unexpected changes in pharmacokinetic behavior, toxic side products, and an antagonism arising from the easy degradation of the polymer under mechanical stress as a result of its ether structure and its non‐biodegradability, as well as the resulting possible accumulation in the body. These possible side effects will be discussed in this Review and alternative polymers will be evaluated.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“However, immunogenicity of PEG depends on the degree of PEGylation to which molecule it is coupled with and have been shown to induce unpredictable complement activation.[ 204 ]”
From Unraveling and Harnessing the Immune Response at the Cell–Biomaterial Interface for Tissue Engineering Purposes (2024) · cites this paper as [204]
In the citing paper
“Incorporating PEG-lipids further decreases recognition by the MPS and clearance by renal filtration17,127.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [127]
In the citing paper
“Moreover, anti-PEG antibodies could result in fast systemic clearance of subsequently administered PEGylated nanoparticles by accelerated blood clearance127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [127]
In the citing paper
“The accelerated blood clearance phenomenon may change the bioavailability and biodistribution of the drug encapsulated in PEGylated nanoparticles and, thus, cause side effects127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [127]
In the citing paper
“To ameliorate safety concerns, numerous natural and synthetic polymers have been investigated as alternatives to PEG, of which several are under evaluation in clinical trials127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [127]
In the citing paper
“Lipid components may activate host immune responses following systemic or local administration; for example, PEG-lipids could induce hypersensitivity reactions by stimulating the complement system127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [127]
In the citing paper
“Lipid components may activate host immune responses following systemic or local administration; for example, PEG-lipids could induce hypersensitivity reactions by stimulating the complement system127,169.”
From Lipid nanoparticles for mRNA delivery (2021) · cites this paper as [127]
Citations
Cites
Items 201–219 of 219
Allergic contact dermatitis from methoxy PEG‐17/dodecyl glycol copolymer (Elfacos® OW 100)
Coz, C. J. L., & Heid, E. (2001) · Contact Dermatitis · doi:10.1034/j.1600-0536.2001.044005308.x · Cited by 25
Romberg, B., Flesch, F. M., Hennink, W. E., & Storm, G. (2007) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2007.11.055 · Cited by 25
Investigation of the thermal decomposition of poly(2-hydroxypropyl methacrylate)
Demirelli, K., Çoşkun, M., Kaya, E., & Çoşkun, M. (2002) · Polymer Degradation and Stability · doi:10.1016/s0141-3910(02)00182-9 · Cited by 21
The Future of Biotechnology Testing in the Next Decade: A Perspective
Johnson, D. E. (2001) · International Journal of Toxicology · doi:10.1080/109158101750103314 · Cited by 20
Angioedema as a hypersensitivity reaction to polyethylene glycol oral electrolyte solution
Assal, C., & Watson, P. Y. (2006) · Gastrointestinal Endoscopy · doi:10.1016/j.gie.2006.02.008 · Cited by 18
Ranucci, E., Ferruti, P., Annunziata, R., Gerges, I., & Spinelli, G. (2006) · Macromolecular Bioscience · doi:10.1002/mabi.200500225 · Cited by 18
Ultrafine Hydrogel Nanoparticles: Synthetic Approach and Therapeutic Application in Living Cells
Gao, D., Xu, H., Philbert, M. A., & Kopelman, R. (2007) · Angewandte Chemie · doi:10.1002/ange.200603927 · Cited by 18
Nanorheology of Aqueous Polyethylene Glycol (PEG)
Zhang, X., & Granick, S. (2002) · Macromolecules · doi:10.1021/ma011626s · Cited by 17
Preliminary experiments on polymer degradation in a turbulent shear field
White, D. A. (1970) · Chemical Engineering Science · doi:10.1016/0009-2509(70)80002-1 · Cited by 16
Soo, P. L., Dunne, M., Liu, J., & Allen, C. J. (2008) · Springer eBooks · doi:10.1007/978-0-387-77668-2_12 · Cited by 16
Anaphylaxis to polyethylene glycol (PEG) in a multivitamin tablet
Kwee, Y. N., & Dolovich, J. (1982) · Journal of Allergy and Clinical Immunology · doi:10.1016/s0091-6749(62)80463-1 · Cited by 11
Contrast Echocardiography and Clinical Safety
Calvo, D., de la Hera, J. M., & Lee, D. (2006) · Revista Española de Cardiología (English Edition) · doi:10.1016/s1885-5857(06)60782-2 · Cited by 9
Contraste ecocardiográfico y seguridad clínica
Calvo, D., de la Hera, J. M., & Lee, D.-H. (2006) · Revista Española de Cardiología · doi:10.1157/13087068 · Cited by 8
Clothing dermatitis from Naphthol AS
Coz, C. J. L., & Lepoittevin, J. (2001) · Contact Dermatitis · doi:10.1034/j.1600-0536.2001.044006366.x · Cited by 8
Kwon, O. H., Nho, Y. C., & Lee, Y. M. (2003) · Journal of Industrial and Engineering Chemistry · Cited by 7
Succinoylated Poly[N-(2- Hydroxyethyl)-L-Glutamine] Derivatives for Drug Delivery
Winne, K. D., Roseeuw, E., Pagnaer, J., & Schacht, E. H. (2004) · Journal of Bioactive and Compatible Polymers · doi:10.1177/0883911504048327 · Cited by 7
Shibaev, L. A., Melenevskaya, E. Y., Моисеевич, Г. Б., Yakimanskii, A. V., Ratnikova, O. V., & Gribanov, A. V. (2008) · Journal of Macromolecular Science Part B · doi:10.1080/00222340701849038 · Cited by 5
Acute hypersensitivity to dentifrice
Ito, M., Watanabe, D., Kobayashi, M., Tamada, Y., & Matsumoto, Y. (2006) · Contact Dermatitis · doi:10.1111/j.0105-1873.2006.0775k.x · Cited by 5
Flagged first, then by citations
Research works printed but not linked: 13
- Bhadra D., 2002, Pharmazie, 57, 5
- Woodle M. C., 1990, Proc. Int. Symp. Controlled Release Bioact. Mater., 17, 77
- 2007, Encyclopedia of Polymer Science and Technology
- Kwon O. H., 2003, J. Ind. Eng. Chem., 9, 138
- Le Coz C.‐J., 2001, Contact Dermatitis, 44, 308
- J. M. Metselaar Dissertation Dept. Pharmaceutics Utrecht Institute for Pharmaceutical Sciences Utrecht University The Netherlands 2006.
- de Groot M. C. H., 2004, Ned. Tijdschr. Geneeskd., 148, 1887
- Hinds K. D., 2005, Biomaterials for Delivery and Targeting of Proteins and Nucleic Acids
- 10.1021/ie070287 · DOI
- Li C., 1999, Clin. Cancer Res., 5, 891
- Li C., 1998, Cancer Res., 58, 2404
- You E. S., 2007, J. Ind. Eng. Chem., 13, 219
- 10.1021/ma052593 · DOI
Cited by
Sorted by citations
Cancer nanomedicine: progress, challenges and opportunities
Shi, J., Kantoff, P. W., Wooster, R., & Farokhzad, O. C. (2017) · Nature Reviews Cancer · doi:10.1038/nrc.2016.108 · Cited by 5,873
PEGylation as a strategy for improving nanoparticle-based drug and gene delivery
Suk, J. S., Xu, Q., Kim, N., Hanes, J., & Ensign, L. M. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2015.09.012 · Cited by 4,523
Lipid nanoparticles for mRNA delivery
Hou, X., Zaks, T., Langer, R., & Dong, Y. (2021) · Nature Reviews Materials · doi:10.1038/s41578-021-00358-0 · Cited by 4,076
Kamaly, N., Yameen, B., Wu, J., & Farokhzad, O. C. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00346 · Cited by 3,070
Nanoparticles in Photodynamic Therapy
Lucky, S. S., Soo, K. C., & Zhang, Y. (2015) · Chemical Reviews · doi:10.1021/cr5004198 · Cited by 2,999
Metadata
- Authors
- Knop, K., Hoogenboom, R., Fischer, D., & Schubert, U. S.
- Affiliations
- Dutch Polymer Institute (NL)
- Friedrich Schiller University Jena (DE)
- Venue
- Angewandte Chemie International Edition
- Publisher
- Wiley
- Published
- 2010-07-20
- Volume
- 49
- Issue
- 36
- Pages
- 6288-6308
- ISSN
- 1433-7851 (ISSN-L)
- 1521-3773
- OpenAlex
- W2164841185
- Cited by
- 3,533
- References
- 219
- Citations by year
- 2026: 176 · 2025: 207 · 2024: 191 · 2023: 213 · 2022: 255 · 2021: 270 · 2020: 259 · 2019: 260 · 2018: 277 · 2017: 234 · 2016: 275 · 2015: 254 · 2014: 206 · 2013: 180 · 2012: 159
- FWCI
- 7.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Angewandte Chemie International Edition (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- polyethylene glycol, PEGylation, stealth polymers, polymeric drug delivery, hypersensitivity, pharmacokinetics, polymer degradation
- MeSH terms
- Biocompatible Materials, Drug Carriers, Pharmaceutical Preparations, Polyethylene Glycols, Polymers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
