Adv Polym Sci (2013) 262: 167–190
DOI: 10.1007/12_2013_235
© Springer-Verlag Berlin Heidelberg 2013
Published online: 5 October 2013
From Biocompatible to Biodegradable:
Poly(Ethylene Glycol)s with Predetermined
Breaking Points
Carsten Dingels and Holger Frey
Abstract Poly(ethylene glycol) (PEG) is the gold standard polymer for biomedical
applications. PEG is known for its biocompatibility and antifouling properties and
is widely used for bioconjugation. However, like other synthetic polymers in the
field, PEG is not biodegradable, limiting its use for parenteral formulations and
protein conjugation to a molecular weight range with a specific upper limit (commonly 40–60 kDa) to avoid polyether accumulation in human tissue. For these
biomedical applications, but also for other purposes such as cleavable hydrogels
and templates for porous membranes, several routes for the insertion of in-chain
biocleavable moieties, such as acetals or disulfides, into PEG have been developed.
Recently, the synthetic strategies have been extended from step-growth polymerizations of commercially available, telechelic PEGs to more sophisticated
routes based on ethylene oxide (co)polymerizations, permitting the incorporation
of predetermined breaking points at any position in the PEG chains.
Keywords Acetals Á Biodegradation Á Drug delivery Á PEGylation Á Poly(ethylene
glycol) Á Polyether
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
2 Synthetic Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
2.1 Modification of Commercial PEGs . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . 172
2.2 EO Polymerization Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
C. Dingels and H. Frey (*)
Institut fu ¨r Organische Chemie, Johannes Gutenberg-Universita ¨t Mainz, Duesbergweg 10-14,
55099 Mainz, Germany
e-mail: hfrey@uni-mainz.de
DOI: 10.1007/12_2013_235
© Springer-Verlag Berlin Heidelberg 2013
Published online: 5 October 2013
From Biocompatible to Biodegradable:
Poly(Ethylene Glycol)s with Predetermined
Breaking Points
Carsten Dingels and Holger Frey
Abstract Poly(ethylene glycol) (PEG) is the gold standard polymer for biomedical
applications. PEG is known for its biocompatibility and antifouling properties and
is widely used for bioconjugation. However, like other synthetic polymers in the
field, PEG is not biodegradable, limiting its use for parenteral formulations and
protein conjugation to a molecular weight range with a specific upper limit (commonly 40–60 kDa) to avoid polyether accumulation in human tissue. For these
biomedical applications, but also for other purposes such as cleavable hydrogels
and templates for porous membranes, several routes for the insertion of in-chain
biocleavable moieties, such as acetals or disulfides, into PEG have been developed.
Recently, the synthetic strategies have been extended from step-growth polymerizations of commercially available, telechelic PEGs to more sophisticated
routes based on ethylene oxide (co)polymerizations, permitting the incorporation
of predetermined breaking points at any position in the PEG chains.
Keywords Acetals Á Biodegradation Á Drug delivery Á PEGylation Á Poly(ethylene
glycol) Á Polyether
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 168
2 Synthetic Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
2.1 Modification of Commercial PEGs . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . 172
2.2 EO Polymerization Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 173
C. Dingels and H. Frey (*)
Institut fu ¨r Organische Chemie, Johannes Gutenberg-Universita ¨t Mainz, Duesbergweg 10-14,
55099 Mainz, Germany
e-mail: hfrey@uni-mainz.de