Biomaterials, Biodegradables and Biomimetics Research Group

Conference Abstract -ISI Web of Science Indexed

Intracellular Methylprednisolone Release to Glial Cells Using An Engineered Dendrimer Nanoparticle System


Objectives: SCI therapies do not present effective solutions due to the lack of
efficiency of the drugs used. One possible approach to circumvent this could
be the use of cell-specific intracellular drug delivery systems that could act on
the neuroprotection and regeneration of the lesion. Thus, we are proposing the
use of a dendrimer-based nanoparticle system composed of a polyamidoamine
(PAMAM) core and grafted with carboxymethylchitosan (CMCht). These
nanoparticles will be loaded with methylprednisolone (MP), an anti-inflammatory
corticosteroid that would be carried to the site of lesion.
Methods: CMCht/PAMAM dendrimer nanoparticles (NPs) were synthesized
and MP was incorporated. MP-loaded NPs were labeled with fluorescein
isothiocianate (FITC) to evaluate internalization and intracellular trafficking.
Particle size and zeta potential analysis were performed using the Zetasizer
equipment. MP release profile was assessed by HPLC in two different buffer
solutions (pH 5.0 and pH 7.4). Finally, glial and microglial cultures were
established to evaluate the NPs behavior when in contact with these cells.
Results: MP-loaded NPs possess diameters around 109 nm and are stable at
physiological pH. They do not affect glial cells viability or proliferation. Also, they
were easily internalized by all CNS cell types reaching 100% internalization 24
hours after NPs addition. MP release profile revealed an initial burst within the
first 24 hours followed by a sustained release for periods up to 14 days. The antiinflammatory
profile of these NPs was assessed in microglial cell cultures. The MP
released from the NPs induced a significant decrease on microglial viability.
Conclusions: These results indicate that these dendrimer-based NPs have
potential to be used as modulators of the inflammatory events in SCI sites.
Additionally, they are excellent intracellular delivery carriers, entering the
cells at high rates and releasing the incorporated drug within its cytoplasmic
compartment, and allowing its action to be carried out.

The International Journal of Artificial Organs
dendrimer nanoparticles, glial cells, intracellular delivery
Open Access
Peer Reviewed
Year of Publication
Date Published
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