Biomedical Engineering Reference
In-Depth Information
it was known previously that the carboxylic groups (-COOH) of
HA are the recognition sites for HA receptors and hyaluronidases,
chemical modifications of HA-COOH would change its biological
behaviours in the body [17]. As pointed out by Zhong and co-
workers [17], the enzymatic degradation was delayed with increasing
degree of HA modification. Based on these findings, we and several
other groups designed and generated several HA functional blocks
to self-assemble and encapsulate siRNA and chemotherapeutic
drugs to deliver to the cancer cells efficiently. As HA is too anionic,
siRNA encapsulation directly into the polymer is almost impossible.
Hydrophobic modification of the HA backbone with a fatty acid
chain through a coupling reaction with the carboxylic acid group
of HA not only reduces the negative charge on the surface, but also
helps the derivative to self-assemble into particles. Increasing the
number of nitrogens in the fatty acid chain further neutralises the
negative charge and improves the siRNA encapsulation [16]. It has
also previously been published that these modified HA derivatives
preferentially accumulate in the liver after systemic administration.
In an attempt to address this, polyethylene glycol (PEG)-modified
HA blocks have been used along with the other HA derivatives.
In particular, the PEG surface enables nanoparticles to escape the
reticulo-endothelial system, thus minimising their removal at the
liver site [18].
3.3. Combinatorial-designed Hyaluronic Acid
Nanoparticles
3.3.1 Design of Multifunctional Hyaluronic Acid-based
Delivery Systems
We have synthesised a library of functionally different self-assembling
CD44 targeting HA-based macrostructures by varying the carbon
chain length, nitrogen content and polyamine side chain grafting
onto the HA backbone [19]. The modification of the anionic HA
polymer resulted in effective lowering/shielding of its negative charge
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