The development of drug delivery systems (DDS) for targeted intracel-

lular delivery of therapeutic agents has been attracting great deal of

attention. In traumatic central nervous system conditions, where thera-

pies have been revealing to be highly inneficient and non-specific, these

targeted DDS could be highly beneficial. We have previously shown

in vitro studies where the carboxymethylchitosan (CMCht)/ poly(amido-

amine) (PAMAM) nanoparticles (NPs) were able to be uptaken by dif-

ferent cell types (neurons and glial cells), while not evidencing any

cytotoxicity. In the present study, in vivo biodistribution of the CMCht/

PAMAM NPs was investigated. Following intravenous injection in adult

male Wistar rats, the NPs showed to be stable in circulation and able to

be internalized by cells from different tissues (e.g., brain, liver, kidney

and lung). Afterwards, methylprednisolone (MP)-loaded fluorescently-

labelled NPs were administered in the cerebrospinal fluid of the cis-

terna magna of adult male Wistar rats. Upon the intracisternal injec-

tion, NPs were detected throughout the cortical and parenchimal areas

of the brain, namely in the prefrontal cortex, hippocampus and peri-

ventricular areas after 24 h. More recently, ongoing studies are focusing

on the therapeutic value of these methylprednisolone-loaded NPs

administered following a spinal cord lesion in rats. Significant differ-

ences in the BBB locomotory test were found in MP-NPs treated rats 1monthafterinjury