Biomedical Engineering Reference
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glucuronic carboxylate residue of HA to aminated magnetic NP
using 2-chloro-4,6-dimethoxy-1,3,5-triazine as the coupling agent.
These HA coated magnetic NP were studied on a human monocytic
cell line, THP-1. These cells possess CD44 expression and can be
differentiated into adherent and macrophage-like cells by exposure to
phorbol 12-myristate 13-acetate which serves as a model for human
macrophages [69]. In this study it was observed that the magnetite
core was transiently present inside the cell; however the fluorescein
conjugated to HA was observed in the nucleus. This indicated that
HA coated superparamagnetic iron oxide nanoparticles (SPION) can
be utilised for nuclear drug delivery without inducing the nanotoxicity
associated with the magnetic NP. These HA-coated SPION were
subsequently utilised to deliver Dox to cancer cells. These Dox
loaded HA-SPION were rapidly taken up by cancer cells and the
internalisation of HA-SPION by cancer cells was much higher than
the NP without HA coating. Dox loaded NP (Dox-HA-SPION) was
much more potent than free Dox to kill not only drug-sensitive but
also multidrug-resistant cancer cells [70]. Another most efficient
method to develop HA coated metallic NP is to use dopamine
conjugated HA. Lee and co-workers have successfully utilised the
HA-dopamine conjugate with monodisperse magnetite nanocrystals,
which displayed excellent aqueous stability and CD44 mediated
uptake [71]. MRI of the cells incubated with magnetic nanocrystals
exhibited enhanced relaxation rate in CD44 expressing HCT116
cells over NIH3T3 cells.
8.5 Purification of Hyaluronic Acid Conjugates
HA and other glycosaminoglycans possess several charged functional
groups, such as carboxylates and sulfates. The purification of
bioconjugates derived from these polymers is somewhat tricky and
generally overlooked. The most common method of purification is by
performing dialysis with membranes of suitable pore size in water for
several days. Using organic solvent mixtures like methanol-water or
acetone-water for dialysis is helpful to eliminate organic impurities.
However, with the aminated by-products or substrates present in the
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