Biomedical Engineering Reference
In-Depth Information
3.2.2 Potential of Hyaluronic Acid in Tumour Targeted
Delivery
Tumour targeting activity of HA has a very strong scientific foundation.
As previously discussed, HA is implicated in the metastatic disease
process and many tumours overexpress receptors for HA. Receptor
bound HA is known to be actively internalised by tumour cells where
it is degraded within the lysosomes to oligosaccharides. Owing to its
various important biological functions and excellent physiochemical
properties, HA and modified HA have been extensively investigated
for biomedical applications such as tissue engineering, drug delivery
and molecular imaging [4-6]. In particular, since HA can specifically
bind to various cancer cells that overexpress CD44, studies have
been focused on the applications of HA for anticancer therapeutics
[2, 7-10]. In addition to the targeting ability, the HA polymer also
has several favourable properties to be an excellent delivery vehicle.
It is biodegradable, biocompatible, non-toxic, non-immunogenic
and non-inflammatory, which makes it ideal for a drug delivery
application [2, 11]. This delivery vehicle can also provide protection
to its cargo and imparts solubility to hydrophobic drugs [12-14]. The
shortcomings of using HA, however are that it is rapidly cleared from
the blood circulation by means of recognition by HA receptors in
reticulo-endothelial system organs and degradation by hyaluronidases
[1]. Chemical modifications or ionic complexation of HA allows its
reorganisation into nanoparticles, which reduces HA degradation
and prolongs its circulation time [15]. A relatively simple chemical
structure also allows HA to be further modified to create a wide
range of possible drug delivery carriers.
3.2.3 Manipulating the Properties of Hyaluronic Acid for
Drug Delivery
Various chemical modifications can be performed including
conjugating HA to drug molecules, grafting hydrophobic or cationic
side chains, as well as crosslinking of HA chains into nanogels to
improve the circulation time of the HA derivative [16]. Because
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