Biomedical Engineering Reference
In-Depth Information
O(CH
2
C
H
2
O)
n
C
H
3
NH-PNIPAM
O(CH
2
CH
2
O)
n
CH
3
P
N
P
N
P
N
n
n
n
O(CH
2
CH
2
O)
n
CH
3
(12)
NHCH
2
COOCH
2
CH
3
(13)
NHCH(CH
2
CH(CH
3
)
2
)COOCH
2
CH
3
(14)
NH(CH
2
CH
2
O)
n
CH
3
O(CH
2
CH
2
O)
7
CH
3
O(CH
2
CH
2
O)
7
CH
3
P
N
P
N
P
N
n
n
n
NHCH(CH(CH
3
)CH
2
CH
3
)COOCH
2
CH
3
(15)
GlyPheLeuEt
(16)
GlyPheIleEt
(17)
Fig. 3
Examples of thermosensitive poly(organophosphazenes)
media derived from polymers containing alkyl ether with varying chain length
(
12
) [
107
-
109
]. However, chemical crosslinking by gamma radiation or ultravio-
let irradiation was necessary in order to form thermo-responsive hydrogels. Later,
an amphiphilic graft poly(organophosphazene) containing PNIPAM as hydro-
philic segments and amino acid ester as hydrophobic parts with LCST 32.6 ºC
was synthesized (
13
) [
110
-
112
]. Above its LCST, nanoparticles from the aggre-
gation of self-assembled micelles were formed, which showed the potential as
injectable carriers for the delivery of hydrophobic compounds. Furthermore, the
authors report that the poly(organophosphazenes) do not degrade significantly
during the time-frame of the release experiments, which may limit their biomedi-
cal applications in human body [
112
]. Continued efforts to develop thermosensi-
tive poly(organophosphazenes) led to the discovery of a series of cyclic trimers
[
59
,
103
-
106
] and polymers [
55
,
58
,
62
,
113
,
114
], a) bearing mono-methoxy-
poly(ethylene glycol) (MPEG) and amino acid (
14
) or depsipeptide ester as shown
in Tables
2
and
3
. All the cyclic trimers and polymers showed a LCST in range
of 21.5-98.5 ºC, depending on the kinds of amino acid, length of MPEG and the
mole ratio of the two substituents. The effect of salts, solvents, and surfactants
on the LCST was studied in detail [
15
,
58
,
114
]. Nevertheless, no formation of
reverse thermogelling hydrogels was reported from both cyclic trimers and poly-
mers mentioned above, which exhibited sol-precipitation behavior upon exposure
to an increased temperature.
The ability to impart a reverse themosensitive response sol-gel transition as a
function of temperature in poly(organophosphazenes) was first developed by Song
and coworkers with a typical structure of
15
, NP[(IleOEt)
x
(AMPEG350)
2-x
]
n
[
61
]. Typically, an aqueous solution of
15
with a concentration of 10 wt% exhib-
ited four-phase transitions with temperature gradually increasing: a transpar-
ent sol, a transparent gel, an opaque gel, and a turbid sol as illustration in Fig.
4
.
As x increased from 0.55 to 1.13, the LCST of
15
decreased from 74 to 37 ºC,
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