unit, but the resulting polymers are limited in their payload, unless synthesized by
multistep protection/deprotection protocols. Very recently, a number of strategies
have been employed that rely on custom-made PEGs by EO polymerization,
either from cleavable initiators or with comonomers that introduce cleavable
functionalities (in some cases upon polymer-analogous derivatization). However,
to date, none of the EO-based polymers has been tested regarding their biocompatibility, their degradation in vivo, or their suitability as drug carriers. In conclusion,
the development of (bio)degradable PEGs has become a fast-evolving field of
research that will eventually contribute to a new generation of polymer therapeutics, but will also have an impact on other areas of polymer research and materials
science.
References
1. Staudinger H (1953) Die makromolekulare Chemie. Nobel Lecture: Macromolecular chemistry. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1953/staudinger-lecture.
html
2. Staudinger H, Schweitzer O (1929) U ¨ ber hochpolymere Verbindungen, 20. Mitteil.: U ¨ ber die
Polya ¨thylenoxyde. Ber Dtsch Chem Ges 62:2395–2405
3. Staudinger H, Lohmann H (1933) U ¨ ber hochpolymere Verbindungen. 81. Mitteilung. U ¨ ber
eukolloides Polya ¨thylenoxyd. Justus Liebigs Ann Chem 505:41–51
4. Staudinger H, Lohmann H (1935) U ¨ ber hochpolymere Verbindungen, 125. Mitteil.:
Molekulargewichts-Bestimmungen an hochmolekularen Polya ¨thylenoxyden. Ber Dtsch
Chem Ges 68:2313–2319
5. Staudinger H, Staudinger M, Sauter E (1937) Mikroskopische Untersuchungen an
synthetischen hochmolekularen Stoffen. Z Physik Chem B 37:403–420
6. Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug
Discov Today 10:1451–1458
7. Kjellander R, Florin E (1981) Water structure and changes in thermal stability of the system
poly(ethylene oxide)-water. J Chem Soc Faraday Trans 1 Phys Chem Condensed Phases
77:2053–2077
8. Zalipsky S (1995) Functionalized poly(ethylene glycols) for preparation of biologically
relevant conjugates. Bioconjugate Chem 6:150–165
9. Li J, Kao WJ (2003) Synthesis of polyethylene glycol (PEG) derivatives and PEGylatedpeptide biopolymer conjugates. Biomacromolecules 4:1055–1067
10. Thompson MS, Vadala TP, Vadala ML, Lin Y, Riffle JS (2008) Synthesis and applications of
heterobifunctional poly(ethylene oxide) oligomers. Polymer 49:345–373
11. Dingels C, Scho ¨mer M, Frey H (2011) Die vielen Gesichter des Poly(ethylenglykol)s. Chem
unserer Zeit 45:338–349
12. Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Del Rev 55:1261–1277
13. Greenwald RB, Choe YH, McGuire J, Conover CD (2003) Effective drug delivery by
PEGylated drug conjugates: bioconjugates for effective drug targeting. Adv Drug Del Rev
55:217–250
14. Harris JM, Chess RB (2003) Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov
2:214–221
15. Pasut G, Sergi M, Veronese FM (2008) Anti-cancer PEG-enzymes: 30 years old, but still a
current approach. Adv Drug Del Rev 60:69–78
From Biocompatible to Biodegradable: Poly(Ethylene Glycol)s with. . .
183
multistep protection/deprotection protocols. Very recently, a number of strategies
have been employed that rely on custom-made PEGs by EO polymerization,
either from cleavable initiators or with comonomers that introduce cleavable
functionalities (in some cases upon polymer-analogous derivatization). However,
to date, none of the EO-based polymers has been tested regarding their biocompatibility, their degradation in vivo, or their suitability as drug carriers. In conclusion,
the development of (bio)degradable PEGs has become a fast-evolving field of
research that will eventually contribute to a new generation of polymer therapeutics, but will also have an impact on other areas of polymer research and materials
science.
References
1. Staudinger H (1953) Die makromolekulare Chemie. Nobel Lecture: Macromolecular chemistry. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1953/staudinger-lecture.
html
2. Staudinger H, Schweitzer O (1929) U ¨ ber hochpolymere Verbindungen, 20. Mitteil.: U ¨ ber die
Polya ¨thylenoxyde. Ber Dtsch Chem Ges 62:2395–2405
3. Staudinger H, Lohmann H (1933) U ¨ ber hochpolymere Verbindungen. 81. Mitteilung. U ¨ ber
eukolloides Polya ¨thylenoxyd. Justus Liebigs Ann Chem 505:41–51
4. Staudinger H, Lohmann H (1935) U ¨ ber hochpolymere Verbindungen, 125. Mitteil.:
Molekulargewichts-Bestimmungen an hochmolekularen Polya ¨thylenoxyden. Ber Dtsch
Chem Ges 68:2313–2319
5. Staudinger H, Staudinger M, Sauter E (1937) Mikroskopische Untersuchungen an
synthetischen hochmolekularen Stoffen. Z Physik Chem B 37:403–420
6. Veronese FM, Pasut G (2005) PEGylation, successful approach to drug delivery. Drug
Discov Today 10:1451–1458
7. Kjellander R, Florin E (1981) Water structure and changes in thermal stability of the system
poly(ethylene oxide)-water. J Chem Soc Faraday Trans 1 Phys Chem Condensed Phases
77:2053–2077
8. Zalipsky S (1995) Functionalized poly(ethylene glycols) for preparation of biologically
relevant conjugates. Bioconjugate Chem 6:150–165
9. Li J, Kao WJ (2003) Synthesis of polyethylene glycol (PEG) derivatives and PEGylatedpeptide biopolymer conjugates. Biomacromolecules 4:1055–1067
10. Thompson MS, Vadala TP, Vadala ML, Lin Y, Riffle JS (2008) Synthesis and applications of
heterobifunctional poly(ethylene oxide) oligomers. Polymer 49:345–373
11. Dingels C, Scho ¨mer M, Frey H (2011) Die vielen Gesichter des Poly(ethylenglykol)s. Chem
unserer Zeit 45:338–349
12. Caliceti P, Veronese FM (2003) Pharmacokinetic and biodistribution properties of poly(ethylene glycol)-protein conjugates. Adv Drug Del Rev 55:1261–1277
13. Greenwald RB, Choe YH, McGuire J, Conover CD (2003) Effective drug delivery by
PEGylated drug conjugates: bioconjugates for effective drug targeting. Adv Drug Del Rev
55:217–250
14. Harris JM, Chess RB (2003) Effect of pegylation on pharmaceuticals. Nat Rev Drug Discov
2:214–221
15. Pasut G, Sergi M, Veronese FM (2008) Anti-cancer PEG-enzymes: 30 years old, but still a
current approach. Adv Drug Del Rev 60:69–78
From Biocompatible to Biodegradable: Poly(Ethylene Glycol)s with. . .
183