Biomedical Engineering Reference
In-Depth Information
OR
N
P
n
OR
(9)
Cl
Cl
O
R
P
Cl
N
N
250
o
C
NaOR
NH
2
R'
N
Cl
Cl
N
P
P
n
n
vacuum
P
P
N
Cl
N
HR
'
Cl
Cl
(10)
(7)
(8)
NHR'
N
P
n
NHR'
(11)
Scheme 1
Synthetic route of poly(organophosphazenes)
The significant difference between poly(organophosphazenes) and other poly-
mers from the synthetic point of view lies in the introduction of side groups
after the polymer backbone is assembled. Thus, this macromolecular substitu-
tion allows the introduction of side groups that may not survive a polymeriza-
tion reaction. Also, properties can be controlled by use of different compositions
of side groups or through variations in co-substituent ratios [
99
]. For example,
poly(organophosphazenes) bearing isoleucine ethyl ester (IleOEt) and
ʱ
-amino-
ˉ
-methoxy-poly(ethylene glycol) with molecular weight of 350 (AMPEG350),
NP[(IleOEt)
x
(AMPEG350)
2-x
]
n
, one of the typical structures of the biodegradable
thermogelling poly(organophosphazenes) [
61
,
68
], are synthesized by introducing
the first nucleophile (IleOEt) while the progress of the reaction is being monitored
by NMR techniques. After complete reaction of the first nucleophile, an excess of
the second nucleophile (AMPEG350) is added to complete the halogen replace-
ment. The composition of the final products can be easily and precisely controlled
by using different feeding ratio of IleOEt and AMPEG350, leading to a series of
NP[(IleOEt)
x
(AMPEG350)
2-x
]
n
with x from 0.87 to 1.45. In addition, three or four
co-substituents can be introduced into the same poly(organophosphazene) in order
to finely tune the properties as shown in Table
1
. Therefore, the mechanical prop-
erties, biodegradability, and LCST can be controlled by varying the co-substitu-
ents, which will be discussed in the following sections.
The biodegradable thermogelling poly(organophosphazenes) have a molecu-
lar weight of about several 10
4
kDa, much lower than the molecular weight of
poly(alkoxy or aryloxyphosphazenes) which are usually above a million kDa
[
100
,
101
]. The reason is that the introduction of amino side groups involves the
release of hydrogen chloride. Although a strong base such as triethylamine is
used in order to remove the hydrogen chloride generated, the released hydrogen
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