drug delivery systems can be found in a substantial monograph on polyphophoesters published recently [137].
Various PEG-based polyurethanes (PUs) have been synthesized, mainly to
introduce pendant functionalities along the polymer backbone [138–143], and are
usually considered nondegradable under physiological conditions. Biodegradability
has been described for numerous polyurethane materials, but seems to occur
predominantly at additionally present cleavable units. Therefore, poly(ester urethane)s degrade faster than poly(ether urethane)s [162]. Similar findings were
reported for PEG-based PU films using α-chymotrypsin in aqueous, buffered
solution. A sample containing an enzymatically cleavable trypsin chain extender
eroded much faster than a PU film without such a moiety [144]. The hydrolytic
degradation of PEG-based PUs is slow and was investigated on samples
synthesized without any chain extender at pH 7.4 (37
C) (15% reduction of M w
within 12 days) [145].
4 Conclusions and Outlook
Based on several speeches at the end of Staudinger’s career, in which he
emphasized the importance of macromolecular chemistry for the mechanisms of
life, it is a safe bet that the combination of synthetic and biological macromolecules
would have found his strong approval. It is interesting to note that PEG, as one of
the polymers in the focus of his research [2–5], eventually became the gold standard
polymer for biomedical applications and bioconjugation and therefore one of the
major bridges between these fields. Although PEG has been of scientific interest for
several decades, new insights and methods for tuning its properties are of high
current interest.
To tackle PEG’s most important disadvantage in biomedical applications – its
biopersistence – various synthetic pathways have been investigated for inserting
into the backbone of PEG a variety of different degradable moieties that can be
cleaved under conditions found within organisms. Besides polymer therapeutics,
degradable PEGs have also been investigated for the reversible fixation of volatile
scents and the synthesis of cleavable hydrogels. The rate of degradation strongly
depends on the constitution and chemical environment of the linker as well as the
size of the PEG segments. Care has to be taken when comparing the degradation
data for different methods. Main parameters that have to be taken into account are
the temperature, pH, type of enzyme, concentrations (in case pseudo-first-order
kinetics do not apply), and the measured quantity (number of remaining linkers,
amount of released telechelic PEG, residual molecular weight). Although many of
the presented PEGs gave promising results as biodegradable drug carriers, most of
these materials were synthesized in polycondensation reactions and therefore
exhibit certain drawbacks, such as broad molecular weight distributions as a direct
result of the step-growth kinetics. On the other hand, well-defined degradable PEGs
can be obtained by coupling monofunctional PEGs to a (multi)functional labile
182
C. Dingels and H. Frey
Various PEG-based polyurethanes (PUs) have been synthesized, mainly to
introduce pendant functionalities along the polymer backbone [138–143], and are
usually considered nondegradable under physiological conditions. Biodegradability
has been described for numerous polyurethane materials, but seems to occur
predominantly at additionally present cleavable units. Therefore, poly(ester urethane)s degrade faster than poly(ether urethane)s [162]. Similar findings were
reported for PEG-based PU films using α-chymotrypsin in aqueous, buffered
solution. A sample containing an enzymatically cleavable trypsin chain extender
eroded much faster than a PU film without such a moiety [144]. The hydrolytic
degradation of PEG-based PUs is slow and was investigated on samples
synthesized without any chain extender at pH 7.4 (37
C) (15% reduction of M w
within 12 days) [145].
4 Conclusions and Outlook
Based on several speeches at the end of Staudinger’s career, in which he
emphasized the importance of macromolecular chemistry for the mechanisms of
life, it is a safe bet that the combination of synthetic and biological macromolecules
would have found his strong approval. It is interesting to note that PEG, as one of
the polymers in the focus of his research [2–5], eventually became the gold standard
polymer for biomedical applications and bioconjugation and therefore one of the
major bridges between these fields. Although PEG has been of scientific interest for
several decades, new insights and methods for tuning its properties are of high
current interest.
To tackle PEG’s most important disadvantage in biomedical applications – its
biopersistence – various synthetic pathways have been investigated for inserting
into the backbone of PEG a variety of different degradable moieties that can be
cleaved under conditions found within organisms. Besides polymer therapeutics,
degradable PEGs have also been investigated for the reversible fixation of volatile
scents and the synthesis of cleavable hydrogels. The rate of degradation strongly
depends on the constitution and chemical environment of the linker as well as the
size of the PEG segments. Care has to be taken when comparing the degradation
data for different methods. Main parameters that have to be taken into account are
the temperature, pH, type of enzyme, concentrations (in case pseudo-first-order
kinetics do not apply), and the measured quantity (number of remaining linkers,
amount of released telechelic PEG, residual molecular weight). Although many of
the presented PEGs gave promising results as biodegradable drug carriers, most of
these materials were synthesized in polycondensation reactions and therefore
exhibit certain drawbacks, such as broad molecular weight distributions as a direct
result of the step-growth kinetics. On the other hand, well-defined degradable PEGs
can be obtained by coupling monofunctional PEGs to a (multi)functional labile
182
C. Dingels and H. Frey