Biomedical Engineering Reference
In-Depth Information
5.4.2.2 Attachment through Charge-Charge Interaction
One of the most studied inorganic NPs for drug delivery is IOMNP. IOM-
NPs have been Food and Drug Administration approved for human use
in the form of the drugs Ferridex, Resovist, Combidex, and AMI-288/feru-
moxytol that are successfully utilized as MRI contrast agents.
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Attachment
of drugs to IOMNPs can be done through charge-charge interaction using
carboxyl- or amine-surface modification.
Dox is one of the most commonly studied drug for NP delivery because it
offers several advantages for research aside from its use as an effective antican-
cer drug. The hydrochloride form of dox is water soluble, it is fluorescent, and
can be monitored before and after loading into the NP. Purification to eliminate
excess or unloaded dox can be accomplished through centrifugation, dialysis,
or magnetization.
Procedure for charge-charge loading of dox on NMs
(All the procedures in this topic are for research purposes only.)
(1)
Take 100 mg of carboxyl-surface-modified IOMNP and disperse in physi-
ological saline (0.15 M NaCl, pH 7.0-7.5).
(2)
Take doxorubicin hydrochloride and dissolve in physiological saline at 0.1
to 2 mg/mL depending upon the loading of the drug required.
(3)
Follow the Table below for loading dox at various ratios on IOMNP.
(4)
Incubate with shaking at RT for at least 60 min.
(5)
Remove excess dox by centrifugation, dialysis, or magnetization. The cen-
trifugation speed needs to be optimized depending upon the size of the
IOMNPs. The MW cutoff of the dialysis tubing also needs to be chosen
based on the size of the IOMNPs. Magnetization is recommended for
≥25 nm but not for <25 nm because the process may take more than 24 h.
(6)
Resuspend the IOMNPs (
Figure 5.4
) in the physiological saline solution
and refrigerate until use.
To check the efficiency of loading of the dox in IOMNPs, place the IOMNP-
dox in saline at pH 2-5. Incubate at RT for 30 min with gentle shaking. Mag-
netize or centrifuge to precipitate the IOMNPs. Measure the absorbance or
fluorescence signal from the dox.
Figure 5.4
shows the 10-nm IOMNP loaded
with dox (top) followed by the supernatant after release of the dox at pH 4.
The bottom contains the saline used to wash the IOMNPs after the release of
the dox. The supernatant contained minimal amount of dox compared with the
supernatant solution.
5.4.2.3 Attachment through HI
Attachment through HI can be achieved with hydrophobic NMs and hydropho-
bic drugs through physical association of targeting ligands to the nanocarrier
surface. HI has the advantage of eliminating the use of rigorous and potentially
destructive chemicals that weaken the efficacy of the drugs. However, there are
