Descrição
In living organisms, there are phenomena that require the presence of
specific biomolecules with distinct function and in variable concentra-
tions at a given time, such as the healing and regeneration of tissue
and organ lesions. In this work, we propose the use of a compartment-
ed drug delivery device for the multiple release of bioactive agents. It
consists of nanostructured microcapsules confined within a millimetric
container that can be easily handled, mimicking the concept of cells
which possess organelles with specialized functions. Each hierarchical
structure was conceived using the layer-by-layer (LbL) method to form
micro and macrocapsules that could individually carry either molecules
and release them with distinct kinetics or magnetic nanoparticles
(MNPs) to be used in targeted therapies. Furthermore, the internal
microcontainers were constructed with a temperature-responsive elas-
tin-like recombinamer (ELR) to further add smart properties to the pro-
posed system. Sacrificial CaCO3 microparticles empty or entrapping
either rhodamine or Fe3O4 MNPs were incubated in chitosan and ELR
solutions using LbL for the conception of the microcapsules. Then, the
microcapsules were suspended in alginate which was ionically cross-
linked in CaCl2 drop-wise. Rhodamine could be encapsulated at this
point in the alginate. The bead was coated with chitosan and alginate
to build the external macrocapsule compartment. All structures were
coated with 3 bilayers. The CaCO3 cores were chelated and the alginate
beads liquefied using EDTA. Fluorescence microscopy using FITC and
rhodamine markers showed a uniform distribution of the microcap-
sules within the macroreservoir. The release of rhodamine from either
in the micro or macrocapsule was assessed at 25 and 37 °C in PBS.
While the release from the macrocapsule follows a profile similar to
that of traditional drug delivery systems, it is more sustained and
delayed when released from the internal compartments. Such retention
is more pronounced at 37 °C (65% of release in comparison to 90%).
This is due to the temperature responsive behavior of ELRs, which
undergo a phase transition and make the LbL shell less permeable. For
the magnetic response, the incorporation of the MNPs was observed by
transmitted light microscopy. The attraction of the devices was
observed by applying an external magnetic field along a defined trajec-
tory. The results let foresee the use of such multilayer devices as com-
partmented structures to encapsulate growth factors, MNPs and stem
cells for their controlled differentiation and maintenance or for guided
regeneration of tissues and organs.
; Castro, E. 
