Hyaluronic Acid-based Scaffolds for Brain Tissue Engineering - Hyaluronic Acid for Biomedical and Pharmaceutical Applications - page 128

release formulation of protein drugs. Hydrophilic HA hydrogel
networks can be exploited as a depot for sustained release of
protein drugs without denaturation. In addition, HA has excellent
physicochemical properties such as its biocompatibility, and non-
immunogenic, non-inflammatory, and completely biodegradable
characteristics.
Strategies for delivery of neurotrophic factors using HA-based
scaffolds have been investigated. An injectable hydrogel for drug
delivery has been developed by Shoichet's laboratory, composed
of a physical blend of HA and methylcellulose (MC), which could
undergo gelling at body temperature for in situ CNS therapy.
The material has been shown to be biocompatible, bioresorbable and
to attenuate inflammation in the CNS [39, 40]. The HA-MC system
for the delivery of growth factors to the stroke injured brain has also
been used for repairing the injured spinal cord [41, 42]. Hydrophilic
proteins diffused through the HA-MC matrix typically within 24 h.
To obtain an extended release profile for these therapeutic agents, the
factors are loaded into PLGA nanospheres which are then dispersed
within the HA-MC. Although proteins diffuse in vitro through the
particles and through the gel alone quite quickly, the combination of
the two gives a non-intuitive linear release profile with a low burst
release [43]. Hydrophobic drugs, such as the vasodilator nimodipine,
have been dispersed in their solid form directly in HA-MC. MC
helps to solubilise hydrophobic drugs from five to ten fold over their
normal solubility in aqueous solution [44]. This allows an extended
release profile that can be tailored by changing the size of the solid
drug particles.
Considering the formation of glial scarring that could inhibit axon
regeneration, researchers have been paying more attention to using
HA-based scaffolds to deliver antibodies to the growth axonal growth
inhibitors (e.g., Nogo, MAG and OMgp) or their receptors. Studies
have shown that sustained delivery of the Nogo-66 receptor antibody
(anti-NgR) into the brain tissue after injury blocked the inhibition
of neurite outgrowth by myelin-associated glycoprotein (MAG) in
a dose-dependent manner, which was effective in overcoming the