Biomedical Engineering Reference
In-Depth Information
(p = 0.005), and a 3.6-fold enhancement in the target selectivity index of nanopar-
ticle accumulation in glioma over the normal brain (p = 0.025). In the magnetically
targeted animals, the glioma retention of MNPs persisted for
∼
100 min following
removal of the external magnetic fi eld.
10.3.1.3
PEG - Coated MNP s via the Coprecipitation Method
A one-pot synthesis of MNPs coated with copolymers of PEG has also been
reported [29, 30]. The iron oxide nanoparticle dispersions were prepared by copre-
cipitation of Fe
2+
and Fe
3+
from an aqueous solution by a base in the presence of
the graft copolymer. One of the copolymers of PEG used was poly(glycerol
monoacrylate)-
g
- poly(PEG methyl ether acrylate) ( PGA -
g
- PEG ) [29] . PGA -
g
- PEG
was prepared by the acid hydrolysis of poly(solktal acrylate)-
g
- poly(PEG methyl
ether acrylate), which was synthesized via the copolymerization of solktal acrylate
and PEG methyl ether acrylate by atom transfer radical polymerization (ATRP).
The size of the superparamagnetic magnetite nanoparticles could be controlled
from 4 to 18 nm by varying the graft density of the copolymers.
In another method, the poly(oligo(ethylene glycol) methacrylate-
co
- methacrylic
acid) (P(OEGMA-
co
-MAA)) copolymer was used [30]. This copolymer was prepared
via a two-step procedure: a well-defi ned precursor poly(oligo(ethylene glycol) meth-
acrylate-
co
-
tert
- butyl methacrylate), P(OEGMA -
co
-
t
BMA) (M
n
= 17 300 g mol
− 1
; M
w
/
M
n
= 1.22), was fi rst synthesized by ATRP in the presence of the copper (I)
chloride/2,2
-bipyridyl catalyst system, and subsequently selectively hydrolyzed in
acid conditions. The resultant P(OEGMA-
co
-MAA) was directly utilized as a poly-
meric stabilizer in the MNP synthesis via the coprecipitation of iron salts method.
The diameter of the MNPs could be tuned in the range 10- 25 nm by varying the
initial copolymer concentration. The PEGylated MNPs exhibited a long-term col-
loidal stability in physiological buffer. Intravenous injection into rats showed no
detectable signal in the liver within the fi rst 2 h, while maximum liver accumula-
tion was found after 6 h, providing indirect proof of a prolonged circulation of the
MNPs in the bloodstream.
A third copolymeric system used for the one-pot synthesis of polymer-coated
MNPs comprised a “ surface anchoring moiety ” 3 - (trimethoxysilyl)propyl methac-
rylate ( TMSMA ) and a protein - resistant PEG methacrylate ( PEGMA ) moiety [31] .
The poly- (TMSMA -
r
-PEGMA) is a random copolymer synthesized from TMSMA
and PEGMA by a radical polymerization reaction [32]. The ferrous and ferric
chlorides were mixed with poly(TMSMA-
r
-PEGMA) before addition of the base to
precipitate the nanoparticles. An external magnetic fi eld was applied to the solu-
tion using a rare earth magnet to separate the MNPs from the remaining unre-
acted polymer in solution. After washing with distilled water, the MNPs were
heated at 80 °C for 1 h to achieve crosslinking between the entangled polymer
chains on the particle surface. The core sizes of the coated MNPs were in the range
of 4-8 nm, with a hydrodynamic diameter of 16 nm. The poly(TMSMA-
r
- PEGMA) -
coated MNPs dispersed well in phosphate-buffered saline (PBS) over a range of
pH conditions (pH 1-10). In addition, DLS data revealed that their sizes were not
altered even after 24 h of incubation in 10% serum containing cell culture medium,
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