3. INTRODUCTION
A drug or therapeutic radionuclide is bound to or
co-incorporated along with magnetic compound and introduced
in to human body, then concentrated in the target area by
means of a magnetic field (using an internally implanted
permanent magnet or an externally applied field) is called as
magnetic drug delivery.
Drug release can proceed by simple diffusion or take place
through mechanisms requiring enzymatic activity or changes in
physiological conditions such as pH, osmolality, or temperature.
Drug release can also be magnetically triggered from the drugconjugated magnetic nanoparticles.
Magnetic targeting is of active targeting with the application of
physical force(magnetic force).
4.
The magnetic nanoparticles can be used for hyperthermia
applications, due to the heat they produce in an alternating
magnetic field The resulting temperature increase can be used
to modify or inhibit specific cell activities locally, or even to
release drugs in a precisely controlled, temperature-increase
activated manner.
Magnetic nanoparticles can also serve as contrast agents for
diagnostic applications such as magnetic resonance imaging.
Magnetic nanoparticles possess many characteristics that make
them promising as drug carriers and for use in biomedical
applications.
5.
Few of biochemical applications are summarized as below
The accumulation of magnetic nanoparticles can be used on its
own to starve the target tissue of oxygen, produce hypoxia and
induce necrosis in tumor cells (Gkiozos I et al ., 2007).
6.
With respect to lung disease, aerosol delivery of drugs by
inhalation represents the most straight forward strategy for
targeting the diseased tissue (Patton JS et al., 2005).This
approach of ‘targeted dose intensification’ for human lung cancer
therapy has been attempted in only a few previous studies.
Dames et al. in their study have brought aerosol delivery to an
advanced level of specificity by using magnetism to direct
magnetizable aerosol droplets specifically to desired regions of
the lungs.
To date, magnetic drug targeting has been explored mostly in
pre-clinical models for cancer therapy with intravascular
administration of ‘magnetic’ drug formulations.
7.
A schematic presentation of the concept of magnetic drug
targeting to tumor tissue on intravascular administration is
shown below.
Magnetic drug targeting with intravascular administration
8.
‘Nanomagnetosols’, as Dames et al. call their compositions for
magnetic drug targeting via the airways, can be generated easily
with state-of-the-art nebulizers that are in clinical use and contain
an appropriate quantity of iron oxide nanoparticles. These make
them susceptible to magnetic field guidance.
Targeted delivery of magnetic aerosol droplets
9.
The nanomagnetosol approach might allow more-specific targeting
of diseased lung areas not only in cancer but also in the case of
infectious lung diseases (Sharma S et al., 2001) .
The fact that plasmid DNA can be magnetically targeted to specific
regions of the lung via nanomagnetosols generates an interesting
link to a method known as ‘magnetofection’, (Plank C et al., 2005)
is a method of magnetic drug targeting applied to nucleic acids.
This would be an exciting extension to the current options for
In vivo gene delivery.
The amount of magnetic nanoparticles per aerosol droplet that
would be required to deflect nanomagnetosols sufficiently by
‘reasonable’ magnetic force in the force-field of an aerosol stream
under the constraints of lung anatomy. ‘Reasonable’ means that
such fields can be generated with affordable equipment with field
strengths that are compatible with clinical application.
10. PROPERTIES OF MAGNETIC MATERIALS
OF PURPOSE.
Superparamagnetic , ferro- and ferri magnetic particles.
Should be deflected in low magnetic field application.
Appropriate surface chemistries and functionalizations is also
important.
High thermal energy.
Non bio-interactive.
Biocompatible.
Nontoxic.
11. MAGNETIC MATERIALS IN USE
Iron oxide based magnetic nanoparticles
1)
superparamagnetic magnetite (Fe304)
2) maghemite (Fe203).
less deflection to magnetic strength at low magnetic field
applications
Cobalt based magnetic nanoparticles
toxicity
Iron based magnetic particles
sensitivity to oxidation
12. ADVANTAGES
Overcomes the natural deposition mechanism of inhaled
aerosol droplets in the lungs that only allows targeting of
the central airways or lung periphery but not local regions
in the lungs.
Offer a degree of flexibility in terms of magnetic drug
formulation that has not previously been possible.
Co-incorporation into aerosol droplets without further
physical association between the drug and nanoparticle.
Achieved
improvements
(magnetofection)
in
nucleic
acid
delivery.
13.
Similar pharmokinetics as would be seen for the drug or gene
vector on its own can be expected.
Used as versatile tools.
Because the magnetic force acting on a magnetic particle is
proportional to the third power of its radius, packaging a
multitude of magnetic nanoparticles in a larger carrier, such as
an aerosol droplet, greatly improves magnetic guidability
Dames et al.
low side effects , low dosing of drug.
14. DISADVANTAGES
Generating sufficient magnetic flux density and field gradient at
the target site, which will be at a distance of at least several
centimeters from the source of the field (e.g. a pole tip)
Even in the presence of higher magnetic force nanomagnetosols
penetration in to deeper lung tissues is limited by inertia for
inhalation nanoparticles.
Exerting sufficient magnetic force on magnetic nanocarriers to
counterbalance hydrodynamic forces has been one of the major
limitations in magnetic drug targeting with intravascular
administration to date.
15.
Particles below 500nm of MMAD are exhaled out (Ally, J. et
al., 2006) .
Iron oxide related toxicity
Accumulation of red blood cells on higher magnetic field
application.
Formation of magnetic agglomerates in case of ferri and ferro
magnetic nanoparticles.
16. RECENT APPLICATIONS
Rudolph C et al., (2005) investigated a novel method
which brings aerosol delivery to an advanced level of
specificity by making use of magnetic gradient fields to
direct
magnetizable
superparamagnetic
iron
aerosol
oxide
droplets
containing
nanoparticles
(SPION)
specifically to desired regions of the lungs in mice.
To target the effected region of cancerous lung in mice
Rudolph C et al., (2005) two independent methods used
to increase and localize aerosol deposition.
SPIONs nebulized through intratracheal aerosol device
and whole-body aerosol device.
17. Representation of the whole-body aerosol device. (a) A plastic box which
houses the mice is connected to the nebulizer via an aerosol spacer placed in
horizontal orientation. The detailed dimensions of the aerosol device are
described in Rudolph et al. . (b) To avoid the mice from adhering together
with their magnets, six small chambers of equal size are inserted into the
box made from a fine non-magnetic mesh. The mesh size should allow
unrestricted aerosol flow.
18. Schematic representation of the FlexiVent respirator(intra tracheal aerosol
device) system used for ventilation and aerosol application.
19. Fixation of a permanent magnet above the thorax of a mouse. The
permanent magnet is fixed on the fur covering the thorax of the
mice by using either tissue glue or any other instant adhesive.
20. CONCLUSION
Magnetic targeting of aerosol streams comprising active
agents could, at the very least, become a valuable research
tool.
In the best case scenario, nanomagnetosols might be
generated entirely from only three clinically approved
components:
approved
drugs,
approved
magnetic
nanoparticles and water or saline. This should greatly
accelerate product development.
21. REFERENCES
Rudolph C et al. Magnetic aerosol targeting of nanoparticles to
cancer: NANOMAGNETOSOLS. Methods Mol Bio. 2010, 624:267-280.
Dames P et al. Targeted delivery of magnetic aerosol droplets to
the lung. Nat. Nano. 2007, 2, 495–499.
Plank C et al. Localized nucleic acid delivery: a discussion of
selected methods. In DNA Pharmaceuticals,2005, pp. 55–116.
Sharma S et al. Development of inhalational agents for oncologic
use. J. Clin. Oncol. 2001, 19, 1839–1847.
Ally, J. et al. Factors affecting magnetic retention of particles in
the upper airways: an in vitro and ex vivo study. J. Aerosol Med.
2006, 19, 491–509
22.
Safarik I et al. Use of magnetic techniques for isolation of cells.
J.Chromatography .1999, B 772:33-53.
Gkiozos I et al. Developments in the treatment of non-small
cell lung cancer. Anticancer Res . 2007, 27(4C), 2823–2827.
Patton JS et al. The lungs as a portal of entry for systemic
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Ferrari M.et al. Applications of magnetic nanoparticles. Nat.
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Cunningham CH et al. Magnetic resonance imaging. Magn.
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23. IF BEING FEASIBLE IS THE ONLY OPTION OF LIFE, THEN THERE
IS NO ‘NO’ FOR ANY WORK. BUT BEING FEASIBLE IS ATYPICAL.
