Biomedical Engineering Reference
In-Depth Information
2-methoxyestradiol [
77
]. A 10 % polymer solution significantly increased the sol-
ubility of 2-methoxyestradiol by about 10
4
times compared to that of PBS solu-
tion. In the in vitro release study, the release mechanism of 2-methoxyestradiol
was mainly dominated by diffusion, hydrophobic interaction, and surface ero-
sion of the matrix. The in vivo antitumor activity of 2-methoxyestradiol-loaded
hydrogels was evaluated by using MDA-MB-231 cell in six-week-old Balb/c
nude female mice. It was found that the hydrogel loaded with 15 mg/kg 2-meth-
oxyestradiol showed the improved antitumor over 4 weeks and antiangiogenic
activity relatively to the original formulation. Similar studies were also conducted
on another anticancer drug, silibinin, using thermosensitive hydrogels based on
polymer
18
as matrix [
78
]. The aqueous solution of polymer
18
enhanced the sol-
ubility of silibinin (0.0415 g/ml) up to 2,000 times, compared with that of PBS
(84.55 mg/ml). In the in vitro degradation study, about 80 % of the hydrogel was
degraded in pH 6.8 media in a month, which was faster than the hydrogel in pH
7.4 with 40 % degradation over 4 weeks. In the in vivo anticancer activity evalua-
tion, the silibinin-loaded hydrogel with a drug concentration of 10 mg/kg showed
the inhibition effect of cancer growth for 40 days just with a single intratumoral
injection. Hence, thermosensitive hydrogel based on poly(organophosphazenes)
exhibit the diversity and feasibility on several different anticancer drugs as an effi-
cient injectable local DDS.
In contrast to the drug release formulation formed by physical mixture between
polymer solution and drugs, a poly(organophosphazene)-drug conjugate hydrogel
has been developed as an improvement for locally controlled delivery of cancer
therapeutics [
63
,
64
,
84
]. An additional functional group, through which a target
anticancer drug can be conjugated in the post modification onto polymer, can be
easily introduced on poly(organophosphazene) backbones during macromolecular
substitution reaction. In this way, improved solubility of hydrophobic drugs, desir-
able pharmacokinetics, and enhanced antitumor activity can be achieved. Also,
multidrug resistance (MDR) will be overcome through slow drug release and an
enhanced permeation and retention (EPR) effect because of the accumulation of
the polymer-drug conjugate within solid tumors [
127
,
128
]. For example, the dox-
orubicin-poly(organophosphazene) conjugates were synthesized through the con-
jugation of doxorubicin with free carboxylic acid on polyphosphazene backbone
(
19
) [
63
]. The resultant conjugates aqueous solution exhibited a sol-gel transition
at body temperature by tuning the hydrophilic-hydrophobic balance through the
composition of co-substituents. Based on the in vivo antitumor activities of the
locally injected conjugate, the conjugate hydrogel (44.5 mg/kg) showed effective
tumor growth inhibition for a prolonged period over 28 days, indicating the active
doxorubicin was released slowly and effectively accumulated locally in the tumor
sites. In addition, polymer
19
was also utilized to form poly(organophosphazene)-
paclitaxel conjugate by a covalent ester linkages between paclitaxel and carboxylic
acid on polymer backbone [
64
]. The conjugates showed a faster degradation and
release profile in acidic condition (pH 6.8) than in neutral condiction (pH 7.4). The
internalized poly(organophosphazene)-paclitaxel conjugate by tumor cells will be
released intracellularly after exposure to lysosomal enzymes or lower pH (4.0-6.5)
Search WWH ::
Custom Search