Biomedical Engineering Reference
In-Depth Information
CDDP or DOX was combined with LGA unit through respective chelation
or electrostatic attraction, and its release from the drug-loaded micellar
nanoparticle was accelerated at the acidic pH, mimicking the endosomal/
lysosomal microenvironment (Figure 15.1B). In an
in vivo
assay towards
A549-bearing female BALB/c nude mice, the CDDP-loaded mPEG-
b
-
PLG micelle showed approximative antitumor ei cacy but signii cantly
lower body weight loss in comparison with free CDDP [42]. Preferably,
mPEG-
b
-PLGA-DOX micellar nanoparticle exhibited both low toxicity
and higher antitumor ei cacy against human NSCLC xenograt ed tumor
model (Figure 15.1C) [41]. Additionally, Chen's group also developed the
grat and block copolymers consisting of PLGA as pH-responsive DOX
carriers for their therapeutic ef ect against hepatic carcinoma [21, 43].
DOX was loaded into micelles through nanoprecipitation, and
in vitro
DOX release was accelerated as either the length of PLGA segment or
pH decreased. Remarkably, the galactosylated DOX-loaded block copoly-
mer exhibited improved antitumor ei cacy against HepG2 cells (a human
hepatoma cell line); conversely, the OEGylated one
in vitro
and
in vivo
exhibited great potential as a highly specii c drug delivery platform for
enhanced chemotherapy ei cacy in human hepatoma [21].
Bae and coworkers have developed the DOX-loaded poly(ethylene
glycol)-
block
-poly(L-histidine) (PEG-
b
-PLH) micellar platforms [44,
45]. h e
in vitro
internalization of DOX toward A2780 cells (a human
ovarian cancer cell line) cultured with the DOX-loaded micelle was
improved more than i ve times by decreasing the pH from 7.4 to 6.8,
which resulted in an enhanced
in vitro
cellular antiproliferative activity
at pH 6.8 [45]. At er being administrated to A2780 xenograt ed nude
mice, the pH-responsive DOX-loaded micelle showed signii cantly
enhanced antitumor ei cacy and markedly increased half-life time com-
pared to free DOX.
In addition, various antitumor drugs (i.e., DOX) have been covalently
conjugated in the polypeptides via acid-labile linkers to fabricate pH-
responsive micelle-like drug delivery systems. Kataoka and coworkers
have developed a PEG-poly(L-aspartate-hydrozone-doxorubicin) (PEG-
b
-P(LA-
H
-DOX)) diblock copolymer, in which DOX was conjugated to
the LA unit via an acid-cleavable hydrazone bond with a substitution ratio
of 67.6 mol% [46, 47]. h e copolymer formed into micelle (~ 65 nm) with
the DOX-conjugated polypeptide segment as a core and PEG block as a
shell. DOX was stably conjugated within the micelles at a pH more than
6.5, whereas the release of DOX was triggered at acidic pH. h e DOX-
conjugated micelle was trapped in endocytic compartments, and exhib-
ited enhanced
in vitro
and
in vivo
antitumor ei cacy toward SBC-3 cells (a
