Biomedical Engineering Reference
In-Depth Information
surface. This allows for a good stability of metal oxide-based nanoparticles in
aqueous solutions. Among the acids most often used to stabilize magnetic iron
oxide-based particle suspensions are citric, tartaric, and dimercaptosuccinic acids
[65-67]. When monomeric anionic stabilizers are used for stabilization purposes,
one critical factor which infl uences stability is the zeta-potential (
), which is the
surface charge at the slipping plane. Thus, charged particles will repel each other
(double-layer repulsion) and produce stable suspensions. Particles with
ζ
−
30 mV
<
+30 mV, at a given pH, are generally found to be stable. For example,
citrate- stabilized 7 nm - diameter iron oxide particles (VSOP - C184 [22] ) have
suffi cient stability - both prior to and on injection - to be used as positive contrast
agents for MRI angiography. As noted previously, however, this application is
dependent on the nanoparticles remaining dispersed, as even a small amount of
aggregation will signifi cantly increase the negative contrast.
ζ
<
4.3.2
Modifi cation Using Polymeric Stabilizers
Most potential nanoparticulate MRI contrast agents are stabilized by polymers
which contain a variety of functional groups, including carboxylic acids, hydroxyls,
phosphates, and sulfates [61]. In this case, the stabilization of nanoparticles can
be achieved due to a group of interactions that are collectively termed steric forces
[68, 69]. Aside from the magnetic interactions, in most cases attractive van der
Waals' forces occur between the polymeric chains, although repulsive contribu-
tions also exist from the osmotic and elastic forces. The former arise from the
unfavorable exclusion of solvent molecules from the interparticle space of two
approaching particles, while the latter is due to the entropic penalty associated
with reduced conformational mobility of the compressed or interdigitated chains
of stabilizer molecules on adjacent particles; hence, this effect operates only at very
short approach distances. In practice, the total force is usually repulsive, and this
results in a stabilization of the particles. When modeling the surface interactions,
the interaction potential is usually expressed as a sum of the three contributions
integrated over the surfaces of the nanoparticles. Usually, the double- layer repul-
sion, which is described by the Derjaguin, Landau, Verwey, and Overbeek (DLVO)
model, is not included [70, 71].
Due to their good solubility in water, biocompatibility, and also permeability,
polysaccharides such as dextran or carboxydextran are among the most popular
polymer coatings used for the stabilization of magnetic nanoparticles. Dextran-
stabilized magnetic nanoparticles can be prepared using a coprecipitation method,
with
in situ
coating by polysacchatide [72]. The most likely mechanism of dextran
adsorption, however, involves collective hydrogen bonding between the dextran
hydroxyl groups and the iron oxide particle surface [73].
Partially oxidized dextran can also be covalently linked to the amino groups of
aminopropylsilane-coated magnetic nanoparticles via the formation of a Schiff 's
base bond [74]. One of the commercially available dextran-stabilized magnetic
fl uids, Ferumoxtran-10 (also known as AMI 227; Sinerem® and Combidex®),
consists of superparamagnetic magnetite cores approximately 5 nm in diameter
