Self-assembled
colloidal gels are highly versatile 3D nanocluster platforms with
potential to overcome the rapid clearing issues associated with standard
free nanotherapeutics administration. However, the development of
nanoassembled colloidal gels exhibiting autonomous multiparticle release
from the bulk particle network remains elusive. Herein, we generated
multiparticle colloidal gels from two nanosized building blocks: cationic
poly(d,l-lactide-co-glycolide)–polyethylenimine
(PLGA–PEI) nanoparticles and anionic zein–hyaluronan
(HA) nanogels that assemble into macrosized 3D constructs via attractive
electrostatic forces. The resulting colloidal gels exhibited high
stability in complex culture medium as well as fit-to-shape moldable
properties and injectability. Moreover, nanoassembled colloidal gels
encapsulated bioactive quercetin flavonoids with high loading efficacy
and presented remarkable anti-inflammatory activities, reducing key
proinflammatory biomarkers in inflammation-activated macrophages.
More importantly, because of their rationally selected building blocks
zein−HA/PLGA−PEI, self-assembled colloidal platforms
displayed autonomous multiparticle shedding. Both positive and negative
particles released from the colloidal system were efficiently internalized
by macrophages along time as evidenced by quantitative particle uptake
analysis. Overall, the generated nanostructured gels represent an
implantable versatile platform for focalized multiparticle delivery.
In addition, the possibility to combine a higher number of particle
species with different properties or stimuli-responsiveness enables
the manufacturing of combinatorial nanostructured gels for numerous
biomedical applications.
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