Biomedical Engineering Reference
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NH(CH
2
CH
2
O)
11
CH
3
NHCH(CH(CH
3
)
CH
2
CH
3
)
COOEt
NH(CH
2
CH
2
O)
11
CH
3
NHCH(CH(CH
3
)CH
2
CH
3
)
COOEt
PN
P
N
PN
P
N
n
n
NHCH(CH(CH
3
CH
2
CH
3
)
COOEt
NHCH
2
COOCH(CH
3
)COOEt
NHCH(CH(CH
3
)CH
2
CH
3
)
COOEt
NHCH
2
CONHCH
2
COOH
(18)
(19)
Fig. 5
Chemical structures of thermogelling poly(organophosphazenes) for drug delivery
bioluminescence, a more sensitive method for measuring tumor load. The study
showed tumor growth was suppressed much more effectively among mice treated
with polymer gel loaded with a dose of doxorubicin (30 mg/kg) compared with
those given intravenous doxorubicin (15 mg/kg). The results indicated that local
intratumoral delivery of doxorubicin with a large dose can be performed by using
poly(organophosaphazenes) thermogels, while restricting its biodistribution to
tumor tissue and reducing systemic exposure and toxicity.
Another widely used antineoplastic drug is paclitaxel. It has been shown to
exhibit a significant activity against various solid tumors. However, due to its
hydrophobicity, paclitaxel shows very poor solubility in water and has hypersensi-
tivity reactions associated with its formulation, containing Chremophor
TM
EL and
ethanol [
126
]. Therefore, an injectable DDS based on poly(organophosphazenes)
thermgels was developed for the local delivery of paclitaxel. Paclitaxel-loaded
hydrogel based on polymer
18
was injected into six-week-old female Balb/c nude
mice with the HSC44Luc human gastric cancer cell line [
87
]. The study showed
that a hydrogel combined with paclitaxel (15 mg/kg) was a more effective treat-
ment for peritoneal carcinomatosis than PBS or hydrogel alone in a mouse model.
Although a paclitaxel solution had a similar antitumor effect, sever side effects
were observed with a higher drug load (30 mg/kg). Furthermore, both human colo-
rectal cancer cell line, DLD-1, and humane gastric cancer cell line, SNU-601 were
also used to evaluate the antitumor efficacy of paclitaxel-loaded hydrogel (
18
).
The in vitro and in vivo release of the formulation with 0.6 % w/w drug and 10 %
w/w hydrgel were found to be 40 and 90 % of the dose over 4 weeks with a sus-
tained manner [
83
]. The local tumor was well controlled for 42 days with a slight
initial burst when used intratumorally. Therefore, a poly(organophosphazene)
hydrogel mixed with anticancer drug, paclitaxel may be a safe and effective treat-
ment for patients with peritoneal carcinomatosis.
Several other anticancer drugs were also evaluated for their effect on the prop-
erties of thermogels, release profile, antitumor efficacy in both in vitro and in vivo.
The polymer solution of
18
can dramatically enhance the solubility of antican-
cer drug, 5-fluorouracil from 3.39 mg/ml in PBS (pH 7.4, 4 ºC) up to 34.26 mg/
ml [
66
]. An increased
T
max
and a decreased
V
max
were observed for the 5-fluo-
rouracil loaded hydrogel. According to the study, the release mechanism of
5-fluororacil from poly(organophosphazene) hydrogels was only a diffusion-con-
trolled drug release. Besides, a prolonged release profile can be achieved by using
poly(organophosphazenes) with higher content of AMPEG, due to the hydro-
philic interaction between 5-fluorouracil and AMPEG segments. Additionally,
polymer
18
was also used to enhance the bioavailability of the antitumor drug,
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