@inproceedings {15748, title = {Dendrimer-based nanoparticle delivery system for the sustained and intracellular delivery of methylprednisolone to CNS cells: potential application in spinal cord injury treatment}, journal = {Histology and Histopathology}, volume = {26}, year = {2011}, month = {2011-07-27 00:00:00}, pages = {323-324}, abstract = {

Spinal Cord Injury (SCI) is a traumatic condition where the
post-trauma regeneration is difficult to accomplish due to
the extremely harsh environment that follows the injury.
One possible approach that could successfully act on the
neuroprotection and/or regeneration of the lesioned area
would be the use of cell-specific intracellular drug
delivery systems. Methylprednisolone (MP) is an antiinflammatory
drug currently employed in the clinical
practice to treat SCI. However, it presents low efficacy
even when used in high doses, causing several adverse
side effects in patients. Thus, we are proposing the use of
a dendrimer-based nanoparticle system composed of a
polyamidoamine (PAMAM) core and grafted with the
natural polymer carboxymethylchitosan (CMCht). Being
so, CMCht/PAMAM dendrimer nanoparticles (NPs) were
synthesized and MP was incorporated in the NPs. MPloaded
NPs were labeled with fluorescein isothiocianate
to evaluate internalization and intracellular trafficking.
Characterization results indicated that MP-loaded NPs
possess diameters around 109 nm and negative zeta
potential values at the physiological pH. When incubated
with glial cells (200μg/ml) the MP-loaded NPs were easily
internalized by all CNS cell types reaching 100\%
internalization 24 hours after NPs addition. MP release
profile was assessed by HPLC. Results revealed an initial
burst within the first 24 hours followed by a sustained
release for periods up to 14 days. Finally, the antiinflammatory
profile of these NPs was assessed in pure
microglial cell cultures using 1 mg/mL and 1.5 mg/mL NPs
addition. The MP released from the NPs induced a
significant decrease on cell viability (around 50\% when
compared to the control). These results indicate that
these NPs might be used to modulate the action of
inflammatory cells in SCI sites. Additionally, as they are
also internalized by astrocytes and oligodendrocytes one
may hypothesize whether the behavior of these cells may
also be modulated by MP-loaded NPs.

}, keywords = {intracellular drug delivery, Nanoparticles, neuroprotection, spinal cord injury}, author = {Cerqueira, S. R. and Oliveira, J. M. and Mano, J. F. and Sousa, N. and Salgado, A. J. and Reis, R. L.} }