Targeted Drug Delivery - Nanomaterials for Medical Applications - page 211

IFN-γ-adsorbed DMSA-coated MNPs can be used as an efficient in vivo drug
delivery system for tumor immunotherapy.
To study the mechanism of cellular uptake, the lymphatic biodistribution of
superparamagnetic NP ferumoxtran, AMI 227/Sinerem™/Combidex was char-
acterized in rats. 172 Within 90 min after catheterization of the thoracic lymph
duct and i.v. injection of ferumoxtran, high concentrations were found by MR
relaxometry and atomic absorption spectroscopy in the thoracic lymph. There
were no NMs found in the lymph cells which indicated that ferumoxtran was
extracellular. 170 The highest concentration of NMs was reached 12 h later in all
node groups and then plateaued thereafter.
In another study, the biodistribution of dox-loaded MNPs was assessed in
mice after i.v. injection. 173 The results of electron spin resonance (ESR) showed
that the dox-MNPs decreased the dox bioavailability in the heart and kidney
compared with the free unconjugated dox. The dox-MNPs bioavailability at the
target site was effectively increased by an applied magnetic field of 210 mT and
gradient of 200 mT/cm which also reduced the hepatic clearance resulting in the
increased plasma bioavailability. 173 This response was attributed to possible in
vivo inhibition of phagocytic cells by the applied magnetic fields.
In a separate study using magnetic vectoring system with more complex
external magnetic fields to target a tumor and enhance tumor extravasation
of systemically administered magnetite-based, silica-coated MNP prodrug
constructs were administred. 174 The biodistribution of magnetite MNPs were
found widely distributed in tissues including the heart, liver, spleen, lungs,
kidneys, brain, stomach, small intestine, and bone marrow, with the majority
in the liver and spleen. Fe 3 O 4 MNP levels in brain tissue were higher in the
MNP-treated group than in the controls, indicating penetration of the BBB.
These observed localization have already been achieved as validated by MRI
and SEM in tumor tissues from human ovarian and breast carcinoma xenograft
models. 175,176
Superparamagnetic Fe 3 O 4 poly e-caprolactone (PCL) NPs (~165 nm) were
prepared by Gang et al. 177 with magnetizations of ~10.2 emu/g. These PCL NPs
showed improved pharmacokinetic behavior. The potential for enhanced anti-
tumor effects were examined in nude mice with subcutaneous (s.c.) xenografts
of human pancreatic adenocarcinoma cells using the PCL NPs that were loaded
with gemcitabine. The magnetic targeting exhibited 15-fold higher intratumoral
drug levels compared with free gemcitabine administration.
The chemoadsorptive properties of activated carbon had been exploited in
the form of silica-coated iron-carbon composite NPs (200-300 nm) for drug
loading and for magnetic iron targeting. 178 Using dox loaded NPs, the dox con-
tent of pig hepatic tissue was ~24-fold higher in the magnetically targeted left
lobe than that in the nontargeted right lobe following intra-arterial infusion. 178
From these observatios, it was suggested that the NPs penetrated through the
capillary wall around the tissue interstitium and hepatic cells under the external
magnetic field.