Biomedical Engineering Reference
In-Depth Information
Tumor remission has been achieved not only in small animals such as rabbits and
rats [118, 120, 121], but also in much larger animals such as swine [122, 123]. For
example, in a study conducted by Alexiou
et al.
[118] , ferrofl uids bound to mito-
xantrone were concentrated in VX-2 carcinomas in New Zealand White rabbits by
using an external magnetic fi eld. The application of an external alternating mag-
netic fi eld resulted in a signifi cant, complete, and permanent remission of squa-
mous cell carcinoma, with no signs of toxicity compared to the control group (no
treatment). Alexiou
et al.
[124] then conducted a follow-up study to investigate the
in vitro
and
in vivo
capabilities of ferrofl uids bound to mitoxantrone, and found
the concentration of the chemotherapeutic agent in the tumor region to be much
higher than with regular, systemic chemotherapy.
Pulfer
et al.
[121] evaluated the ability of uncharged magnetic nanoparticles
(10-20 nm) to target intracerebral rat glioma-2 tumors
in vivo
. In order to deter-
mine the ways in which particle size infl uenced the blood-tumor barrier uptake,
these authors injected nanoparticles (4 mg kg
− 1
) intra-arterially into male Fisher
344 rats bearing rat glioma-2 tumors, and then applied magnetic fi elds of between
0 and 6000 G to the rat brains for 30 min. The animals were killed at either 30 min
or 6 h after injection, and the tissues collected and analyzed for their magnetite
content. It was found that, in the presence of a magnetic fi eld, the nanoparticles
localized in brain tumor tissue at levels of 41% and 48% of the dose per gram of
tissue after 30 min and 6 h respectively, which was signifi cantly greater than their
uptake in nontarget tissues. In the absence of a magnetic fi eld, levels of only 31%
and 23% dose per gram were achieved at the same time points. A TEM analysis
of the brain tissue revealed magnetic nanoparticles in the interstitial space of the
tumors, but only in the vasculature of normal brain tissue. These results suggested
that changes in the vascular endothelium of tumor tissue had promoted a selective
uptake of the uncharged magnetic nanoparticles, and thus provided a basis for the
development of novel drug-loaded nanoparticles as targeted drug delivery systems
for brain tumors.
Goodwin [122, 123] and coworkers used a swine model to investigate drug target-
ing and retention abilities in regions of interest after an intra-arterial infusion of
doxorubicin, coupled to magnetically targeted particles composed of elemental iron
and activated carbon. The placement of an external magnet over the tumor region
enabled an effi cient targeting of the doxorubicin-coupled magnetic particles [105].
Recently, Alexiou
et al.
[124] achieved a degree of success in quantifying the
distribution of magnetically targeted carriers in a rabbit model using a high-
performance liquid chromatography analysis of mitoxantrone bound to ferrofl u-
ids, having demonstrated the uptake of magnetically targeted carriers in HeLa cells
in vitro
. In order to overcome problems associated with the spatial confi guration
of these delivery systems, Kubo
et al.
[125] implanted permanent magnets at solid
osteosarcoma sites in hamsters, and then used magnetoliposomes to deliver cyto-
toxic compounds. These authors discovered a fourfold increase in drug delivery to
the tumor site compared to normal intravenous (nonmagnetic) delivery. Kubo
et al.
also reported a signifi cant increase in antitumor activity and a reduction in
weight-loss-inducing side effects. The use of implanted magnetic grids to target
