Biodegradable Thermogelling Poly(Organophosphazenes) and Their Potential Biomedical Applications - In-Situ Gelling Polymers: For Biomedical Applications - page 53

acid groups on poly(organophosphazene) backbone through covalent linkage.
Protamine was conjugated to polymer 19 by an amide linkage [ 67 ]. The aqueous
solution of the cationic polymer conjugates formed a gel at 37 ºC regardless of
hGH presence. The release studies showed that the hGH loaded hydrogel based
on poly(organophosphazene)-protamine conjugate had a prolonged release period
and the initial burst release was significantly suppressed. In the in vivo pharma-
cokinetic and pharmacodynamic studies, an elevated plasma level of hGH was
induced by a single administration of hGH-loaded hydrogel until 5 days as well
as an increased plasma level of insulin-like growth factor-1 until 13 days. With the
same concept, polyethylenimine (PEI) was also conjugated on polymer 19 to form
cationic poly(organophosphazene)-PEI conjugates [ 86 ]. However, it was reported
that a single administration showed equivalent efficacy with only four days' daily
administration of hGH solution alone.
3.3 Long-Term Magnetic Resonance Contrast Platform
Poly(organophosphazene) thermogels have been utilized as a novel platform for
a long-term imaging system, such as magnetic resonance imaging (MRI) due
to their injectability, biodegradability, localizability, and sustainability [ 79 , 81 ,
82 ]. Thus, it is not compulsory for the intravenous administration of the contrast
agents every time due to the short half-life of the agents in vivo when a medical
imaging diagnosis or a theragnosis is performed. A thermosensitive and magnetic
hydrogel comprising cobalt ferrite (CoFe 2 O 4 ) nanoparticles as contrast agents
and hydrogels based on polymer 18 was designed for long-term magnetic reso-
nance imaging [ 81 ]. The magnetic hydrogel showed extremely low cytotoxicity
and adequate magnetic properties for use in long-term MRI. Approximately 70 %
weight loss of the magnetic hydrogel was observed over 28 days in vitro. In the
in vivo study, the applicable potentiality as a long-term MR contrast platform was
successfully estimated over 4-5 weeks. Later, a long-term theranostic hydrogel
based on polymer 18 , but with longer AMPEG segment, specifically designed for
solid tumors was developed by cooperating both cobalt ferrite nanoparticles and
paclitaxel [ 82 ]. The resultant hydrogel had an approximately 70 % weight loss at
the twenty-eight day. About 71.16 13.34 % of paclitaxel and 93.68 1.06 %
of iron in the theranostic hydrogel were released in vitro. In the in vivo test of
the theramostic hydrogel in solid tumor-bearing nude mice, the increase of tumor
volume was suppressed between the second and third week. Simultaneously, the
long-term MR imaging was also accomplished for the same periods. In addition,
the same magnetic hydrogel but with a different anticancer drug, 7-ethyl-10-hy-
droxycamptothecin, was used as MRI-monitored long-term therapeutic hydrogel
for brain tumors [ 79 ]. The hydrogel can be injected into the area of brain tumor
stereotactically within a very small-sized pin hole to minimize the drawbacks of
surgical treatments.