Biomedical Engineering Reference
In-Depth Information
commercially prepared and utilized for clinical use (e.g., Ferridex® , Combidex ® ,
Resovist®, and AMI-228/ferumoxytrol); all of these particles differ in terms of
their surface coatings, which include dextran, carbohydrate, and citrate [6-8, 22,
33- 38] .
Dextran-coated iron oxide nanoparticles have become an important part of clini-
cal cancer imaging, and have been shown to increase the accuracy of cancer nodal
staging [39-41]. These particles have also been utilized to better delineate primary
tumors [42], to image angiogenesis [43], and in the detection of metastases [44,
45]. The particles have also been used to image the infl ammatory components of
atherosclerosis [46] . A modifi cation of dextranated iron oxide with targeting
ligands, such as antibodies [47], has also been achieved to increase the affi nity of
the nanoparticles for their target tissues. One of the main drawbacks, however, is
that the dextran coating is in equilibrium with the surrounding medium, as it is
not strongly associated with the iron oxide core.
In one report, it was noted that dextran-coated iron oxide nanoparticles had the
crosslinking (caging) of dextran and its amination [48]. The resultant particle,
crosslinked iron oxide (CLIO), allows for a simple functionalization via amide
bond formation, and also offers superb stability under harsh conditions (e.g., a
change in size of the dextran coat to increase circulation time). Although CLIO
has served as an ideal model compound for many experimental applications, is
unlikely to be developed for clinical use, given the epichlorohydrin- induced cross-
linking involved (this is similar to Sephadex particles). In order to circumvent this
situation, magnetic nanoparticle preparations with biodegradable, high- affi nity
coatings are currently being developed by the present authors' group, and by
others.
6.2.3
Physico - Chemical Characterization of MNP s
Previously, MNPs have been characterized using X-ray diffraction (XRD), vibrating
sample magnetometry ( VSM ), scanning electron microscopy ( SEM ), transmission
electron microscopy (TEM), and atomic force microscopy (AFM) [49]. The molecu-
lar weight and number of functional groups on the MNP's surface have been
determined using analytical methods such as gel permeation chromatography
(GPC), nuclear magnetic resonance spectroscopy (NMR), potentiometric titration,
high - performance
liquid
chromatography
(
HPLC ),
and
ultraviolet
(UV)
spectroscopy.
6.2.4
Plasma Stability and Pharmacokinetic Profi le of the MNP s
The biological properties, interaction with plasma proteins, and biodistribution
(monitored as the pharmacokinetic profi le) of the MNPs throughout the body
depends on physico-chemical factors such as particle size, surface charge, protein
adsorption ability, surface hydrophobicity or hydophilicity, drug loading and
