Author(s):
Cerqueira, Susana R.
; Pereira, Vitor H.
; Oliveira, Joaquim M.
; Sousa, Nuno
; Salgado, A. J.
; Reis, R. L.
Date: 2012
Persistent ID: http://hdl.handle.net/1822/24111
Origin: RepositóriUM - Universidade do Minho
Subject(s): Biodistribution; CNS; Nanoparticles
Description
The development of drug delivery systems (DDS) for targeted intracellular
delivery of therapeutic agents has been attracting great deal of
attention. In traumatic central nervous system conditions, where therapies
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(amidoamine)
(PAMAM) nanoparticles (NPs) were able to be uptaken by different
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 fluorescentlylabelled
NPs were administered in the cerebrospinal fluid of the cisterna
magna of adult male Wistar rats. Upon the intracisternal injection,
NPs were detected throughout the cortical and parenchimal areas
of the brain, namely in the prefrontal cortex, hippocampus and periventricular
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 differences in the BBB locomotory test were found in MP-NPs treated rats 1 month after injury.