Author(s):
Cerqueira, Susana R. 
; Oliveira, Joaquim M. ; Mano, J. F. ; Sousa, Nuno ; Salgado, A. J. ; Reis, R. L.
Date: 2013
Persistent ID: http://hdl.handle.net/1822/25640
Origin: RepositóriUM - Universidade do Minho
Subject(s): Nanomedicine; Neuroregeneration; Spinal cord injury
Description
Unlike fish, amphibia and even mammalial peripheral nerves, human central nervous
system (CNS) axons have a very limited regeneration capability and do not
spontaneously re-grow if lesioned. After damage or disruption, for instance caused by
brain/ spinal cord injury (SCI) or stroke, a cascade of cellular and biochemical reactions
occurs around the lesion site that creates a harsh environment for axons to regenerate.
Immune and glial cells around the injury are also responsible for the production of
molecules that restrain the axon re-growth, such as myelin associated inhibitors and
chondroitin sulfate proteoglycans. Additionally, astrocytes and fibroblasts contribute to
the formation of a scar around the damaged tissue that physically blocks axon repair.
Thus, and in view of the latest findings it is imperative to block these inhibitory
reactions and induce a more adequate environment for tissue repair and regeneration.
In our lab, we are currently developing biomaterial-based strategies to repair the injured
CNS, focusing on spinal cord. The absence of effective therapies in SCI repair is in part
due to its extreme complexity, but also to the lack of efficiency and targeting of the
existing drugs. In order to target the detrimental cellular responses that follow the injury
in a more specific and sustained manner, we developed a nanoparticle-based drug
delivery system intended to target glial cells and modulate the inflammatory processes
in SCI. Poly/(amido)amine (PAMAM) dendrimer nanoparticles grafted with
carboxymethylchitosan (CMCht) were loaded with the anti-inflammatory corticosteroid
methylprednisolone. The nanoparticles were shown to be internalized by glial cells
without affecting its metabolic viability, while releasing the drug in a sustained and
prolonged manner. Nanoparticle administration in spinal cord injured rats induced
improved recovery in these animals, suggesting that nanoparticles can limit the damage
extent and contribute to nerve repair/ sparing. We believe that strategies such as this, intending to minimize the secondary events that
follow nervous injury can be an opportunity for successful treatments in CNS tissue
repair.
