This study reports, first, on the preparation and cross-linking
of multilayers composed of poly(2-isopropyl-2-oxazoline-
co
-ethyleneimine) (PiPOX-PEI) and tannic acid (TA). PiPOX was synthesized
by cationic ring-opening polymerization (CROP) and partially hydrolyzed,
yielding a random copolymer PiPOX-PEI. It was then coassembled at
the surface with TA using the layer-by-layer (LbL) technique. Multilayers
were exposed to NaIO
4
solution to induce covalent bond
formation between PEI units of PiPOX-PEI and TA. Cross-linking with
NaIO
4
enhanced the stability of the multilayers, especially
under basic conditions. Second, the potential of PiPOX-PEI and TA
multilayers as a stimuli-responsive dual drug-releasing platform was
examined using curcumin (CUR) and doxorubicin (DOX) as model drugs.
These drugs were chosen as they can act in a combinatorial manner
to increase cell death. The surface of CUR-containing CaCO
3
microparticles was modified with PiPOX-PEI and TA multilayers and
postloaded with DOX. We found
that LbL particles could release DOX in a pH-responsive manner, whereas
temperature-induced release was observed only when the temperature
was raised above 40 °C. The DOX and CUR released from the LbL
particles could act synergistically on HCT-116 cells. Cross-linking
increased the DOX release from LbL particles but decreased the CUR
release from the core. Corroborating the release data, the synergy
observed with the non-cross-linked particles was lost with the cross-linked
particles, and the decrease in the viability of HCT-116 cells was
attributed mainly to the release of DOX. Overall, we describe here
NaIO
4
-induced cross-linking of PiPOX-PEI/TA LbL films,
the effects of pH, temperature, and cross-linking on DOX and CUR release
from multilayers, and comparison of the combinatorial effect of DOX
and CUR for cross-linked and non-cross-linked LbL microparticles through
cell viability assays.
