Biomedical Engineering Reference
In-Depth Information
which is attributed to hydrophobic interactions between the tetralkyl groups of
organic salts and the non-polar side groups of the polymers, leading to ioni-
zation of the side groups [
56
,
71
,
88
]. Furthermore, the gelation property of
poly(organophosphazenes) also depends greatly on pH. As the pH decreased from
7.4 to 3.9, the
V
max
(the viscosity of the polymer solutions at
T
max
) of a neutral poly-
mer significantly decreased and the
T
max
of the polymer increased [
68
,
89
]. This is
due to a change in hydrophilic-hydrophobic balance by protonation in amine groups.
On the other hand, the opposite trend was observed when carboxylic acid groups
were present in a thermogelling poly(organophosphazene). This is due to the fact
that the acidic polymer becomes almost completely neutral at lower pH due to the
protonation of carboxylic acid groups [
88
,
89
]. Moreover, gelation behavior, as well
as the physical properties of thermogelling poly(organophosphazenes), can be also
controlled by adjusting the hydrophobic-hydrophilic balance after polymerization
through the blending of polymers [
57
,
75
,
86
]. By blending polymer
15
and [NP(Ile
OEt)
1.07
(GlyLacOEt)
0.02
(AMPEG550)
0.91
]
n
with a blend ratio of 3 to 1, a transparent
hydrogel with
T
max
at 37 ºC and good gel strength (
V
max
> 200 Pas) was achieved,
which could be effectively utilized as a locally injectable hydrogel. On the contrary,
none of each component exhibited efficient viscosity at 37 ºC individually [
57
].
2.3 Biodegradability and Hydrolysis Mechanism
Poly(organophosphazenes) have long been found to be sensitive to hydrolysis by
incorporating hydrolytically sensitive side groups as illustrated in Fig.
2
, of which
amino acid containing poly(organophosphazenes) resulted in many biodegrad-
able materials for various biomedical applications [
36
,
45
,
116
-
125
]. Thus, one
of the main reasons for understanding the mechanisms of hydrolysis of biodegrad-
able poly(organophosphazenes) is to study the possible toxic intermediates or end
products formed during hydrolysis.
Studies have shown that degradation rate of thermosensitive
poly(organophosphazenes) can be controlled over periods of days to months
by using different hydrophobic moieties, such as amino acid, depsipeptide
and dipeptide, adjusting length of PEG segments and varying the co-substit-
uent composition. Poly(organophosphazenes) containing glycine ester and
MPEG, for an instance, showed a decreased degradation rate in the order of
methyl > ethyl > benzyl esters [
58
]. Polymers substituted with
ʱ
-amino acid esters
hydrolyzed faster than that with
ʲ
-amino acid ester. Also, a more rapid hydroly-
sis occurred in both acidic and basic buffer solutions than in the neutral solution
[
58
]. Additionally, degradation rate can be accelerated significantly by either
incorporating depsipeptide ethyl esters or switching from MPEG to AMPEG seg-
ments [
60
,
68
,
90
,
113
]. The polymers with depsipeptide ethyl esters had half-lives
of less than 10 days at pH 7 and 37 ºC, while the polymers without depsipep-
tide ethyl ester, had a half-life over 40 days [
60
]. On other hand, the half-lives
of [NP(GlyOEt)
0.94
(AMPEG350)
1.06
]
n
at pH 5, 7.4 and 10 were 9, 16 and 5 days,
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