Spinal cord injury severely affects thousands of people every year
worldwide. Current treatments based on pharmacological agents have a
limited efficacy, mainly due to the lack of specificity of the drugs used. To
surmount this problem one could use intracellular drug delivery systems
designed to specifically target a defined cell population and promote
neuroprotection and/or tissue regeneration. It has been recently shown that
carboxymethylchitosan/polyamidoamine (CMC/PAMAM) dendrimer
nanoparticles are easily internalized by CNS cells, which can make them
amenable for the intracellular release of methylprednisolone (MP) to
specific cell populations, namely astrocytes and glial cells, avoiding in this
sense its secondary effects on neuronal cell populations. Therefore the aim
of this work consisted on the surface engineering of a polyamidoamine
dendrimer core with natural-based and biocompatible polymers in order to
obtain novel macromolecules to be employed as targeted and intracellular
MP delivery devices. MP was loaded into the CMC/PAMAM dendrimer
nanoparticles using a precipitation route. FTIR analysis revealed that the
drug was incorporated into the bulk of the CMC/PAMAM dendrimer
nanoparticles. Particle size analysis revealed the MP-loaded CMC/
PAMAM dendrimer nanoparticles have a size ranging between 63 and 155
nm. Moreover, these nanoparticles possess a positive zeta potential at pH 3,
while for pH 6.9, 7.4 and 10 the latter was negative. Finally, the binding of a
F’(a,b) portion of a CD11b antibody to the nanoparticles, in order to render
them a cell targeted profile against microglial cells, was confirmed by UV/
VIS analysis. The biological proof of concept of these MP-loaded CMC/
PAMAM dendrimer nanoparticles is currently under study.
| 
