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.
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