Biomedical Engineering Reference
In-Depth Information
3 Applications of Biodegradable Thermogelling
Poly(Organophosphazenes)
Biodegradable thermogelling poly(organophosphazenes) have been widely used
in various biomedical applications. According to the discussion in the previous
sections, one of the advantages of this system over other currently used thermo-
gelling polymers as injectable in situ forming hydrogels lies on their convenient
tunability of properties depending on different applications by adjusting the type
of hydrophobic moieties, the length of hydrophilic segments and the compo-
sition of substituents. Also, post modification of poly(organophosphazenes)
backbone is possible by introducing additional functional groups during the
macromolecular substitution, which will render the biodegradable thermogelling
poly(organophosphazenes) more flexibility in designing multifunctional thermo-
sensitive hydrogel. In this section, applications of the reverse thermogelling sys-
tem based on poly(organophosphazenes) for drug delivery, bioimaging and tissue
engineering will be reviewed.
3.1 Delivery of Antitumor Drugs
A new drug delivery system (DDS) based on biodegradable thermogelling
poly(organophosphazenes) was developed for intratumoral delivery of chemother-
apeutic agents in order to provide drug localization within the tumor and divert
the drug from non-target organs to reduce toxicity and increase efficacy (Fig.
5
).
Hydrogels formed from poly(organophosphazenes) bearing hydrophobic IleOEt
and hydrophilic AMPEG550 along with hydrolysis-sensitive GlyLacOEt (
18
)
were found to be excellent solubilisers of hydrophobic antitumor drug, doxoru-
bicin, compared with that in phosphate buffered saline (PBS, 0.01 M, pH 7.4)
[
80
]. The aqueous polymer solution with doxorubicin showed a sol-gel transition
at physiological conditions. The release of doxorubicin from the hydrogel system
was significantly sustained over 20 days. The anticancer efficacy of the released
doxorubicin was constant over a prolonged period of times for more than 30 days,
when the P388D1 mouse lymphoblast cell line was evaluated. In another study, the
doxorubicin-loaded hydrogels based on the same poly(organophosphazenes) (
18
)
was evaluated on the human gastric cancer cell line, SNU-601 for their antican-
cer efficacy [
76
]. A sustained release was observed from the formulation of 10 %
w/w of hydrgel and 0.6 % w/w of doxorubicin with 40 and 90 % released over
5 weeks in vitro and in vivo. The hydrogel mass was well retained over 7 weeks
and exhibited excellent local tumor control with a slight initial burst when used
intratumorally. In addition, the anticancer efficacy of doxorubicin load in the
same hydrogels was also evaluated using the human gastric cancer cell line,
HSC44Luc within Balb/c female nude mice [
84
]. The suppressive effects of dox-
orubicin-loaded hydrogels on tumor growth were evaluated by means of in vivo
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