Biomedical Engineering Reference
In-Depth Information
NHS ester was grafted on to hydrazide modified HA which
was subsequently crosslinked with HA aldehyde derivatives
by hydrazone linkage. The drug-loaded hydrogel induced less
inflammation than HA gel without the drug [85]. HA hydrogels
are also used for delivering peptides and therapeutic proteins/
growth factors by conjugating these therapeutic molecules to
HA or by simple mixing. The first method requires additional
HA conjugation before hydrogel preparation which might reduce
the bioactivity of these therapeutic macromolecules, therefore
encapsulating the protein by simple mixing with the hydrogel
component is more efficient for delivering proteins. This strategy is
successfully demonstrated for encapsulating bone morphogenetic
protein-2 which displayed good stability and sustained release
[25]. The
in vivo
evaluation of this hydrogel revealed neobone
formation with a highly ordered collagen matrix mimicking
natural bone regeneration [25]. Other sensitive growth factors
like human basic fibroblast growth factor (FGF-2) can also be
delivered from a HA hydrogel system by conjugating heparin to
the HA hydrogel. As heparin has specific protein binding sites
for FGF-2, heparin containing HA hydrogel displayed controlled
release (60%) over 14 days [30]. Native HA have also been used
for protein delivery. HA and recombinant human insulin were co-
spray dried to form a dry powder suitable for inhalation. Animal
testing revealed that HA microparticles containing insulin (10%
w/w) were found to extend the mean residence time and terminal
half-life when compared to spray dried pure insulin [86].
Physically crosslinked HA hydrogel containing vasoactive intestinal
peptide-loaded liposomes was developed for the treatment of
endotoxin-induced uveitis. Interactions between HA chains and
liposomes increased the viscosity of the gel and resulted in a delayed
release of the vasoactive intestinal peptide [87]. However, the low
stability of HA microparticles and physically crosslinked HA hydrogel
is a limitation for protein delivery applications.
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