Biomedical Engineering Reference
In-Depth Information
DMSO at room temperature, to result in positively charged and pH- responsive
particles. Finally, when a mixture of citric acid and 2-bromo-2-methyl propionic
acid ligands was used, water- soluble (and water - methanol - soluble) particles could
be obtained, on which both polystyrene sulfonate and poly(NIPAAm) brushes
could be grown through ATRP. Amino-functionalized PEG chains could also be
attached to the citric acid-coated nanoparticles using carbodiimide-promoted ami-
dation chemistry.
The surface-initiated ATRP of NIPAAm on MNPs prepared via the high-tem-
perature decomposition of Fe(acac)
3
route can also be achieved by utilizing
2-(4-chlorosulfonylphenyl) ethyltrichlorosilane as the initiator and conducting the
ATRP in DMSO at 40 °C for 10 h [66]. The preserved active chlorine groups on the
MNPs after ATRP of NIPAAm were then used to link up with the heparin mol-
ecules in formamide. The heparinized MNPs retained a high level of magnetiza-
tion (33 emu g
− 1
), and exhibited no signifi cant cytotoxicity towards mouse
macrophages (RAW 264.7). As a result of the inhibitory effect of the bound heparin
on protein adsorption and cell membrane association processes, the heparinized
MNPs were able to delay phagocytosis by the mouse macrophages. The uptake of
the heparinized MNPs by macrophages after 8 h was approximately 30% of that
for the as-synthesized particles. The activity of the immobilized heparin was also
preserved, as illustrated by the effectiveness of the heparinized magnetite nanopar-
ticles in preventing blood clotting
in vitro
. Such MNPs, with an increased plasma
circulation time and antithrombotic properties, may be useful in applications
where the targeted local delivery of heparin is desired, for example in the preven-
tion or reduction of restenosis.
In another surface-initiated ATRP method, a polymeric shell consisting of
NIPAAm crosslinked with PEG 400 dimethacrylate (PEG400DMA) was conferred
on MNPs [67]. Either oleic or citric acid was added to the MNPs immediately after
coprecipitation from the mixed ferric and ferrous salts by ammonium hydroxide
to obtain hydrophobic (oleic acid-coated) or hydrophilic (citric acid-coated) nanopar-
ticles. Subsequent ligand exchange of the oleic acid coating with 2 - bromo - 2 - methyl
propionic acid (BMPA), and the citric acid coating with either 2-bromopropionyl
bromide (BPB) or bromopropyl trimethoxysilane (BPTS), provided initiating sites
for the ATRP of NIPAAm in ethanol at 60 °C. The hydrodynamic diameter of oleic
acid-coated particles dispersed in hexane was determined to be approximately
25 nm by DLS measurements, while that of citric acid-coated MNPs dispersed in
deionized water was approximately 70 nm. The particle sizes of the poly(NIPAAm)-
PEG400DMA-functionalized particles in water were all in the range of 150-300 nm,
depending on the ATRP reaction time and the temperature at which the DLS was
conducted. A larger particle size was obtained when the reaction time was 24 h
compared to 12 h, due to an increase in the polymer shell thickness. At lower
temperatures (20-30 °C), the poly(NIPAAm) shell was more hydrated, and this
contributed to the increased hydrodynamic size of the composite. As the tempera-
ture was increased above the LCST of poly(NIPAAm), the polymer shell took on
a collapsed state, and this resulted in the reduced hydrodynamic diameter of the
functionalized particles.
