Polymer
capsules fabricated
via
the layer-by-layer
(LbL) approach have emerged as promising biomedical systems for the
release of a wide variety of therapeutic agents, owing to their tunable
and controllable structure and the possibility to include several
functionalities in the polymeric membrane during the fabrication process.
However, the limitation of the capsules with a single functionality
to overcome the challenges involved in the treatment of complex pathologies
denotes the need to develop multifunctional capsules capable of targeting
several mediators and/or mechanisms. Oxidative stress is caused by
the accumulation of reactive oxygen species [
e.g.
, hydrogen peroxide (H
2
O
2
), hydroxyl radicals
(
•
OH), and superoxide anion radicals (
•
O
2
–
)] in the cellular microenvironment
and is a key modulator in the pathology of a broad range of inflammatory
diseases. The disease microenvironment is also characterized by the
presence of proinflammatory cytokines, increased levels of matrix
metalloproteinases, and acidic pH, all of which could be exploited
to trigger the release of therapeutic agents. In the present work,
multifunctional capsules were fabricated
via
the
LbL approach. Capsules were loaded with an antioxidant enzyme (catalase)
and functionalized with a model drug (doxorubicin), which was conjugated
to an amine-containing dendritic polyglycerol through a pH-responsive
linker. These capsules efficiently scavenge H
2
O
2
from solution, protecting cells from oxidative stress, and release
the model drug in acidic microenvironments. Accordingly, in this work,
a polymeric microplatform is presented as an unexplored combinatorial
approach applicable for multiple targets of inflammatory diseases,
in order to perform controlled spatiotemporal enzymatic reactions
and drug release in response to biologically relevant stimuli.