3 Different Labile Units for Different Triggers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
3.1 Acid-Sensitive PEGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
3.2 Enzymatically Degradable PEGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
3.3 Alternative Labile Groups and Triggers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
4 Conclusions and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Abbreviations
APEG Amino-pendent polyacetal
AROP Anionic ring-opening polymerization
DOX
Doxorubicin
EO
Ethylene oxide
EPR
Enhanced permeability and retention
FDA
Food and Drug Administration
GSH
Glutathione
mPEG Poly(ethylene glycol) monomethyl ether
OLZ
Olsalazin
PDI
Polydispersity index M w /M n
PEG
Poly(ethylene glycol)
PEI
Poly(ethylene imine)
PG
Polyglycerol
PU
Polyurethane
TEG
Triethylene glycol
1 Introduction
[. . .] In biological processes as well, a slight percentage change in a macromolecule can
bring about profound changes in the chemical and physiological behavior of the macromolecular substance.
With these words, Hermann Staudinger referred in his Noble lecture to the
degradability of poly-oxymethylene (POM) in contrast to its α,ω-dimethyl ether
derivative [1], linking the structure–property relation of an entirely synthetic
polyacetal to biological processes. Sixty years later, we realize that his statement
is not only true for the natural macromolecules he had in mind, such as DNA or
proteins, but also for synthetic polymers designed for in vivo applications.
Besides POM, another polyether was intensively studied by Staudinger – poly
(ethylene glycol) (PEG) – as an early example of an “artificial high polymer”.
Staudinger and coworkers contributed key works both on the investigation of the
synthesis of PEG from ethylene oxide as well as on its physicochemical properties
(Table 1) [2–5]. Nowadays, this versatile polyether has become the gold standard
polymer in drug delivery systems. It exhibits a unique combination of desirable
properties rarely found for any other synthetic or natural polymer. PEG is nontoxic,
168
C. Dingels and H. Frey
3.1 Acid-Sensitive PEGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176
3.2 Enzymatically Degradable PEGs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
3.3 Alternative Labile Groups and Triggers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
4 Conclusions and Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 182
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 183
Abbreviations
APEG Amino-pendent polyacetal
AROP Anionic ring-opening polymerization
DOX
Doxorubicin
EO
Ethylene oxide
EPR
Enhanced permeability and retention
FDA
Food and Drug Administration
GSH
Glutathione
mPEG Poly(ethylene glycol) monomethyl ether
OLZ
Olsalazin
PDI
Polydispersity index M w /M n
PEG
Poly(ethylene glycol)
PEI
Poly(ethylene imine)
PG
Polyglycerol
PU
Polyurethane
TEG
Triethylene glycol
1 Introduction
[. . .] In biological processes as well, a slight percentage change in a macromolecule can
bring about profound changes in the chemical and physiological behavior of the macromolecular substance.
With these words, Hermann Staudinger referred in his Noble lecture to the
degradability of poly-oxymethylene (POM) in contrast to its α,ω-dimethyl ether
derivative [1], linking the structure–property relation of an entirely synthetic
polyacetal to biological processes. Sixty years later, we realize that his statement
is not only true for the natural macromolecules he had in mind, such as DNA or
proteins, but also for synthetic polymers designed for in vivo applications.
Besides POM, another polyether was intensively studied by Staudinger – poly
(ethylene glycol) (PEG) – as an early example of an “artificial high polymer”.
Staudinger and coworkers contributed key works both on the investigation of the
synthesis of PEG from ethylene oxide as well as on its physicochemical properties
(Table 1) [2–5]. Nowadays, this versatile polyether has become the gold standard
polymer in drug delivery systems. It exhibits a unique combination of desirable
properties rarely found for any other synthetic or natural polymer. PEG is nontoxic,
168
C. Dingels and H. Frey