Biomedical Engineering Reference
In-Depth Information
PEO (5 kDa)-PCL (18 kDa) copolymer. Although triblock copolymers
will be covered in a following section, it is worthwhile to note that
72% of paclitaxel was loaded into the PEO (5 kDa)-PCL (18 kDa)-
PEO (5 kDa). It is likely that a PCL (18 kDa)-PEO (5 kDa)-PCL (18
kDa) triblock would be superior in paclitaxel loading. However, this
copolymer upon radical polymerization would likely phase separate
from solution. Therefore, the diblock copolymer with the largest
PCL core would remain the best option for a potential paclitaxel
formulation. Aside from paclitaxel, there are some anticancer
compounds that have a series of derivatives, which each have
diff erent levels of cytotoxicity.
Cucurbitacins, a family of STAT3 onco-signaling inhibitors, or
have an interesting trend where derivatives' cytotoxicity is linearly
related to hydrophobicity [55]. In this case, it may be feasible to
utilize the same core with diff erent block lengths for a series of
derivatives. Molavi
et al
. investigated the release, and
in vitro
and
in
vivo
activity of cucurbitacin I and B from PEO-PCL and poly(α-benzyl
carboxylate ε-caprolactone)(PBCL)-PEO micelles. The addition of
a benzylic carboxylate functional group to the PCL core increases
the lipophilicity, and thus smaller block lengths compared with
conventional PCL may facilitate similar thermodynamic affinities
of the target drug to the core. A series of diblock copolymers
employing a PEO block length of 5 kDa, PCL blocks of 5 or 24 kDa,
or PBCL at 4.7 kDa were utilized to encapsulate cucurbitacin I and B.
Cucurbitacin B diff ers only in an acetyl group in place of a hydroxyl
at the 25
¢
position of cucurbitacin I [56]. Therefore cucurbitacin
B has an axis of symmetric polarity, and is slightly more lipophilic
than cucurbitacin I. The loading efficiency increases with PCL block
length for both derivatives (~30-65%). However a substantial
increase in efficiency occurs with cucurbitacin B in the 4.7 kDa PBCL
core (92%) over cucurbitacin I (74%). This increase could be due to
the greater lipophilicity of cucurbitacin B. All release profiles were
Fickian, and the PEO-PCL (5 kDa) and PEO-PBCL (4.7 kDa) profiles
were nearly identical for both derivatives. At 8 h, approximately
all of the cucurbitacin I had been released, whereas 40-60% of
cucurbitacin B was released. The sustained release of cucurbitacin B
could be due to its lower polarity increased affinity for the non-polar
core. Cucurbitacin I in PEO-PCL (24 kDa) was more potent (IC50 of
10 μM) than cucurbitacin B (IC50 of 50 μM) against a B16.F10 cell
line (melanoma of C57/black origin) after 24 h. For both derivatives
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