Biomedical Engineering Reference
In-Depth Information
On the other hand, Jin and co-workers encapsulated doxorubicin
(Dox) in their amphiphilic polymer micellar system that was composed
of hydrophilic HA and hydrophobic ceramide (CE) [24]. Both HA and
CE have been reported to have several favourable properties for use
as drug delivery systems. These authors managed to conjugate CE to
the HA oligomers to make an amphiphilic HA derivative. Then they
successfully encapsulated the hydrophobic Dox into the hydrophobic
core of the hyaluronic acid-ceramide (HACE)-based NP by a solvent
evaporation method. These particles are highly negatively-charged,
just like the particles that we made with cisplatin, due to the ionised
carboxylic group of HA being located in the shell. This property
implies that the aggregation could be prevented by electrostatic
repulsion. Considering several of the properties that these HA
particles have, it was very clear that these could be used as efficient
anti-cancer drug delivery systems. Interestingly, another group used
HA as a targeting ligand to specifically target tumours [25]. To do
that, they conjugated lower MW HA to pre-formed liposomes. As
known previously, liposomes have the capabilities to encapsulate
both hydrophobic and hydrophilic drugs. Eliaz and Szoka together
for the first time demonstrated the delivery of chemotherapeutics
to cancer cells by HA-modified liposomes [26]. They demonstrated
nicely that the Dox-encapsulated HA-modified liposomes were much
more potent than the Dox alone treatment. It was clear from these
data that the drug reaches the critical compartment more efficiently
than the free form. Targeting cancer cells using higher MW HA
bound liposomes however was first demonstrated by Peer and his
group [27-29]. He and his colleagues showed that the loading of
chemotherapy drugs such as Dox or mitomycin C (MMC) into high
MW HA particles generated a 100-fold increase in drug potency in
cells that overexpress CD44, but not in cells with poor expression of
CD44. This group demonstrated elegantly how the affinity towards
the CD44 receptors was controlled by adjusting the molecular weights
of NP surface HA from weak binding for low MW HA to binding
with higher affinity for high MW HA using their library of lipid NP
(
Table 3.2
).
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