Biomedical Engineering Reference
In-Depth Information
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n
4
y
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Figure
11.6
Synthesis
and
assembly
process
of
NK012.
(Reproduced
from
Matsumura
60a
with permission from Elsevier.)
11.3.3 Drug Polymers
An alternative to using the drug molecules themselves as a part of the
nanocarrier is to directly use biofunctional drug molecules as monomers to
prepare backbone-type polymer-drug conjugates, or drug polymers. One such
example is polycurcumin (PCurc; Figure 11.7).
65
Inspired by the bihydroxyl
functionality of the curcumin molecule, curcumin was used as a co-monomer
to make the curcumin-containing PCurc by polycondensation polymerization.
A series of water-soluble PCurcs were prepared with different covalent bonds
(e.g., ester, disulfide, acetal) with high and fixed curcumin-loading content and
efficiency in comparison with previously developed curcumin-loading nano-
medicines.
66
For instance, curcumin was condensed with divinyl ether to
produce linear polycurcumin linked via acetal bonds. To make the polymer
water soluble, PEG-diol was used as a co-monomer. Water-soluble poly-
curcumin, PCurc 8, could contain up to 25 wt% curcumin. The polymers were
stable at neutral conditions, but hydrolyzed rapidly at lysosomal pH to release
curcumin (Figure 11.7A), causing high toxicity to three cancer cell lines (even
more cytotoxic than the parent curcumin itself) (Figure 11.7B) and remarkable
antitumor activity in the SKOV-3 intraperitoneal xenograft tumor model
(Figure 11.7C).
Another drug polymer we developed is the platinum(IV)-coordinated
polymer using the platinum(IV) prodrugs DHP and DSP as co-monomers
