addition to acrylates, as well as reactions of PEG with the corresponding acids [97],
acid anhydrides [86], acyl chlorides [90–94], and methyl carboxylates [30,
98–102]. Commonly, the polycondensation is conducted during the esterification
step, but the thiol oxidation of PEG cysteine diesters [89] and Michael addition of
dithiols to PEG di(meth)acrylates [95, 96] were also used to synthesize PEG
polyesters. Due to the numerous PEG-based polyesters synthesized for a wide
range of applications, we will focus on the works that studied the PEG polyester
degradability. Depending on the synthetic pathway and the size of the batched
telechelic PEGs, polyesters with molecular weights in the range of 1,000104,500 g mol
À1 and typical PDIs of 1.4-2.7 were generated. The ester-containing
PEGs can undergo enzymatic degradation, but only a few of them were examined
regarding this property [87, 91–93, 104]. Mero et al. observed almost no ester
cleavage in a pH 7.4 buffer at 37
C in 24 h, but rapid degradation in mouse plasma
within the same time [93]. Typically, the enzymatic degradation at 37
C and neutral
pH takes a few days to complete, but comparison of the results is difficult because
too many parameters vary (enzymes, linkers, PEG content, size of the PEG
segments, observed quantity, type of sample). Carboxylates can further be degraded
by simple hydrolysis under both acidic and basic conditions. In theory, degradation
rates are expected to be lowest under neutral conditions; however, in the presence of
basic moieties, the hydrolysis can be slower in more acidic media (Fig. 4) [86, 89,
104]. Not surprisingly, hydrophilic poly(ether ester)s are hydrolyzed faster than
hydrophobic derivatives under the same conditions [72, 88].
Fig. 4 Degradation of PEG cystine polyester at 37
C: Hydrolytic cleavage of ester moieties at
different pH values (solid symbols). Reduction of disulfides at pH 5.5 (c GCH ¼ 5 mmol)
(diamonds). From [89]. Copyright Wiley-VCH. Reproduced with permission
180
C. Dingels and H. Frey
acid anhydrides [86], acyl chlorides [90–94], and methyl carboxylates [30,
98–102]. Commonly, the polycondensation is conducted during the esterification
step, but the thiol oxidation of PEG cysteine diesters [89] and Michael addition of
dithiols to PEG di(meth)acrylates [95, 96] were also used to synthesize PEG
polyesters. Due to the numerous PEG-based polyesters synthesized for a wide
range of applications, we will focus on the works that studied the PEG polyester
degradability. Depending on the synthetic pathway and the size of the batched
telechelic PEGs, polyesters with molecular weights in the range of 1,000104,500 g mol
À1 and typical PDIs of 1.4-2.7 were generated. The ester-containing
PEGs can undergo enzymatic degradation, but only a few of them were examined
regarding this property [87, 91–93, 104]. Mero et al. observed almost no ester
cleavage in a pH 7.4 buffer at 37
C in 24 h, but rapid degradation in mouse plasma
within the same time [93]. Typically, the enzymatic degradation at 37
C and neutral
pH takes a few days to complete, but comparison of the results is difficult because
too many parameters vary (enzymes, linkers, PEG content, size of the PEG
segments, observed quantity, type of sample). Carboxylates can further be degraded
by simple hydrolysis under both acidic and basic conditions. In theory, degradation
rates are expected to be lowest under neutral conditions; however, in the presence of
basic moieties, the hydrolysis can be slower in more acidic media (Fig. 4) [86, 89,
104]. Not surprisingly, hydrophilic poly(ether ester)s are hydrolyzed faster than
hydrophobic derivatives under the same conditions [72, 88].
Fig. 4 Degradation of PEG cystine polyester at 37
C: Hydrolytic cleavage of ester moieties at
different pH values (solid symbols). Reduction of disulfides at pH 5.5 (c GCH ¼ 5 mmol)
(diamonds). From [89]. Copyright Wiley-VCH. Reproduced with permission
180
C. Dingels and H. Frey