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Magnetically modulated Drug Delivery Systems: An Overview

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 Research J. Pharm. and Tech. 4(11):Nov. 2011

ISSN 0974-3618 www.rjptonline.org

REVIEW ARTICLE
Magnetically modulated Drug Delivery Systems: An Overview
Rajendra Jangde*
University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G.)
*Corresponding Author E-mail: rjangdepy@gmail.com

ABSTRACT:
A number of novel drug delivery systems have emerged encompassing various routes of administration, to achieve
controlled and targeted drug delivery, magnetic microcarriers being one of them. These microcarriers include magnetic
microspheres, magnetic liposomes, magnetic nanoparticles, magnetic resealed erythrocytes, magnetic emulsion etc.
Magnetic micro/nanoparticles and molecular magnetic labels have been used for great number of application in various
areas of biosciences, targeted drug delivery, imaging and in bio separation technology. These projects will discuss
about principle of magnetic targeting, mechanism of magnetic targeted drug delivery, benefits and drawbacks of
magnetic targeting, magnetic microcarriers and application of magnetism in targeted drug delivery and some other
field. Magnetically targeted drug delivery by particulate carriers is an efficient method of delivering drugs to localized
disease sites such as tumours. High concentrations of chemotherapeutic or radiological agents can be achieved near the
target site without any toxic effects to normal surrounding tissue. Non-targeted applications of magnetic microspheres
and nanospheres include their use as contrast agents and as drug reservoirs that can be activated by a magnet applied
outside the body. Historic and current applications of magnetic microspheres will be discussed, as well as future
directions and problems to be overcome for the efficient and beneficial use of magnetic carriers in clinical practice.

KEYWORDS: Magnetic microspheres, Nanospheres, nanocarries, microcarriers.

INTRODUCTION: ADVANTAGES OF MAGNET TARGETING: 3

Drug targeting is the delivery of drugs to receptors or
organ or any other specific part of the body to which one
wishes to deliver the drug exclusively. Delivery of drugs is
an important component of the treatment of diseases both
from a commercial and a scientific point of view, as the
method by which a drug is delivered can have a significant
effect on its efficacy. Scientifically, it is extremely
challenging, as the goal is to find a drug-delivery system
with the capability for site-specificity as well as controlled
release1.
Magnetic targeting has several advantages, which includes:
• Therapeutic responses in the target organs at only one
tenth of the free drug dose.
• Controlled drug release within target issues for
intervals of 30 min to 30 hrs.
• Avoidance of acute drug toxicity directed against
endothelium and normal parenchymal cells.
• Adaptable to any part of the body.
• This drug delivery system reduces circulating
concentration of free drug by a factor of 100 or more.

Magnetic Drug Targeting means the specific delivery of
chemotherapeutic agents to their desired targets, e.g. tumors
by using magnetic nanoparticles (ferrofluids) bound to these
agents and an external magnetic field which is focused on
the tumor. This type of target directed drug injection
attempts to concentrate a pharmacologic agent by
enhancing its efficacy while simultaneously minimizing
deleterious side effects2.
Received on 18.09.2011 Modified on 25.09.2011
Accepted on 03.10.2011 © RJPT All right reserved
Research J. Pharm. and Tech. 4(11): Nov. 2011; Page 1649-1657
DISADVANTAGES OF MAGNET TARGETING: 4
This novel approach suffers from certain disadvantages also
as given below:-
• Magnetic targeting is an expensive, technical approach
and acquires specialized manufacture and quality control
system.
• Its needs specialized magnet for targeting, advanced
techniques for monitoring, and trained personnel to perform
procedures.
• Magnet must have relatively constant gradients, in
order to avoid focal over dosing with toxic drugs.
• A large fraction (40-60%) of magnetite, which is
entrapped in carriers, is deposited permanently in target
tissues.
• Drug cannot be targeted to deep seated organs in the
body, so this approach is confined to the targeting of drugs

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 Research J. Pharm. and Tech. 4(11):Nov. 2011

in superficial tissue only like skin, superficial tumour or to and then stopped with a powerful magnetic field in the
joints only target area. The magnetic fields are believed to harmless to
biological system and adaptable to any part of the human
Principles of magnetic targeting:- body. Up to 60% of an injected dose can deposited and
Magnetic drug delivery by particulate carriers is a very released in controlled manner in selected non
efficient method of delivering a drug to a localized disease reticuloendothelial organs (i.e not in liver / spleen / bone
site. Very high concentrations of chemotherapeutic or marrow).7
radiological agents can be achieved near the target site, such
as a tumour, without any toxic effects to normal Magnetic Drug Targeting: Mechanism:
surrounding tissue or to the whole body. Fig. 1 highlights Magnetic drug delivery by particulate carriers is a very
the concept of magnetic targeting by comparing systemic efficient method of delivering a drug to localized disease
drug delivery with magnetic targeting. In magnetic site. Magnetic drug transport technique is based on the fact
targeting, a drug or therapeutic radioisotope is bound to a that the drug can be either encapsulated into a magnetic
magnetic compound, injected into a patient’s blood stream, microsphere (or nanosphere) or conjugated on the surface of
and then stopped with a powerful magnetic field in the the micro/nanosphere. When the magnetic carrier is
target area.5 Depending on the type of drug, it is then slowly intravenously administered, the accumulation takes place
released from the magnetic carriers (e.g. release of within area to which the magnetic field is applied and often
chemotherapeutic drugs from magnetic micro-spheres) or augmented by magnetic agglomeration. The accumulation
confers a local effect (e.g. irradiation from radioactive of the carrier at the target site allows them to deliver the
microspheres; hyperthermia with magnetic nanoparticles). drug locally. Efficiency of accumulation of magnetic carrier
It is thus possible to replace large amounts of freely on physiological carrier depends on physiological
circulating drug with much lower amounts of drug targeted parameters eg. Particle size, surface characteristic, field
magnetically to localized disease sites, reaching effective strength, and blood flow rate etc. The magnetic field helps
and up to several-fold increased localized drug levels. to extravasate the magnetic carrier into the targeted area.
Magnetic carriers receive their magnetic responsiveness to a Very high concentration of chemotherapeutic agents can be
magnetic field from incorporated materials such as achieved near the target site without any toxic effect to
magnetite, iron, nickel, cobalt, neodymium– iron–boron or normal surrounding tissue or to whole both us possible to
samarium–cobalt. Magnetic carriers are normally grouped replace large amounts of drug targeted magnetically to
according to size. At the lower end, we have the ferrofluids, localized disease site, reaching effective and up to several
which are colloidal iron oxide solutions. Encapsulated fold increased drug levels.8
magnetite particles in the range of 10–500 nm are usually
called magnetic nanospheres and any magnetic particles of
just below 1–100 nm are magnetic microspheres. In
generals, magnetic liposome’s are also included when
speaking about magnetic carriers.6

Fig. 2. Concept of magnetic drug targeting.

Fig. 1. Principle of magnetic targeting

Flowchart of principle of magnetic targeting:-

The principle of magnetic targeting by comparing systemic Fig.3. Various nonmagnetic micro carries (nanoparticles,
drug delivery with magnetic targeting. In magnetic microspheres and microparticles etc.) are successfully utilized for
targeting, a drug or therapeutic radioisotope is bound to a drug targeting but they show poor site specificity and are rapidly
magnetic compound, injected into a patient’s blood stream, cleared off by RES (reticuloendothelial system)

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 Research J. Pharm. and Tech. 4(11):Nov. 2011
Magnet design:
The force exerted by a gradient magnetic field is an
important parameter that governs in magnetic targeting of
microcarries. The relationship of magnetic force to field
gradient and magnetic moment of particles is expressed by
following equation: 9
F = M H:
Where, f is force on particles; M is magnetic movement of
particles after saturation magnetism; H is magnetic field
gradient
This equation explains that spheres with increased magnetic
moment will experience force sufficient for extra vascular
migration at proportionately lower field gradients. The
Magnetic, moment of microsphere magnetic can be
increased in three ways
1. By magnetizing the spheres to saturation levels prior to
vascular targeting.
2. By clustering magnetite at the centre of each sphere to
produces large macro domains
3. By substituting one of the newer ferromagnetic materials
that as higher susceptibility than Fe3O4.
The acute and chronic toxicities of several new magnetic
alloys must be assessed before using them in delivery
devices.
Magnetically modulated microcarriers:
Magnetic microcarriers are site specific and by localization
of these microcarriers in the target area, the problem of their
rapid clearance by RES is also surmounted. Linear blood
velocity in capillaries is 300 times less i.e.0.05cm/sec as
compared to arteries, so much smaller magnetic field, 6-8
Koe, is sufficient to retain them in the capillary network of
the target area10. Magnetic carrier technology appears to be
a significant alternative for the bimolecular malformation
(i.e. composition, inactivation or deformation).These
microcarriers includes :-
A) Magnetic microsphere
B) Magnetic liposomes
C) Magnetic nanoparticles
D) Magnetic Resealed Erythrocytes
E) Magnetic Emulsion
F) Biomodulators
G) Magnetic neutrophils
A) Magnetic microspheres:
Magnetic microspheres are supramolecular particles that are
small enough to circulate through capillaries without
producing embolic occlusion (<4 m) but are sufficiently
susceptible (ferromagnetic) to be captured in microvessels
and dragged in to the adjacent tissues by magnetic fields of
0.5-0.8 tesla (T). Magnetic microspheres were prepared by
mainly two methods namely phase separation emulsion
polymerization (PSEP) and continuous solvent evaporation
(CSE). The amount and rate of drug delivery via magnetic
responsive microspheres can be regulated by varying size of
microspheres, drug content , magnetite content , hydration
state and drug release characteristic of carrier. The amount
of drug and magnetite content of microspheres needs to be
1651
delicately balanced in order to design an efficient
therapeutic system. Magnetic microsphere are characterized
for different attributes such as particle size analysis
including size distribution ,surface topography, and texture
etc. using scanning electron microscopy (SEM), drug
entrapment efficiency, percent magnetite content, and in
vitro magnetic responsiveness and drug release.11
Targeting by magnetic microspheres i.e. incorporation of
magnetic particles in to drug carriers (polymers) and using
an externally applied magnetic field is one way to
physically direct this magnetic drug carriers to a desired
site, Widder first reported on the use of magnetic albumin
microspheres.12
Fig 4. Magnetic targeting of Antitumour Microspheres to
pancrease
B) Magnetic liposomes:
Liposomes are simple microscopic vesicles in which lipid
bilayer structures are present with an aqueous volume
entirely enclosed by a membrane, composed of lipid
molecule. There are a number of components present in
liposomes, with phospholipids and cholesterol being the
main ingredients but in case of magneto liposomes
magnetite is one of the component of the liposomes.
Generally these are magnetic carrier which can be prepared
by entrapment of Ferro fluid within core of liposomes.
Magneto liposome can also be produced by covalent
attachment of ligands to the surface of the vehicles or by
incorporation of target lipids in the matrix of structural
phospholipids.13 Alternatively magnetoliposomes are
prepared using the phospholipid vesicle as a nanoreactor for
the in situ precipitation of magnetic nanoparticles. Vesicles
are also prepared containing didodecyl methyl ammonium
bromide; contain an ionic magnetic fluid. These
magnetoliposomes were effectively used for site specific
targeting, cell sorting and as magnetic resonance contrast
enhancing agent. Thermo sensitive magnetoliposomes can
release the entrapped drug after selective heating caused by
the electromagnetic fields. Magneto fluorescent liposomes
were used for increasing sensitivity of immune
fluorescence. The magneto liposomes are characterized for
their physical attributes i.e. size, shape, and size
distribution, surface charge, percent capture, percent
 Research J. Pharm. and Tech. 4(11):Nov. 2011

magnetite content, entrapped volume lamellarity through D) Magnetic Resealed Erythrocytes:

freeze fracture microscopy and P-NMR, phase behavior
drug release, quantitative determination of phospholipids
and cholesterol analysis.14
C) Magnetic nanoparticles:
Magnetic nanoparticles (MNPs) possess unique magnetic
properties and the ability to function at the cellular and
molecular level of biological interactions making them an
attractive platform as contrast agents for magnetic
resonance imaging (MRI) and as carriers for drug delivery.
Recent advances in nanotechnology have improved the
ability to specifically tailor the features and properties of
MNPs for these biomedical applications. To better address
specific clinical needs, MNPs with higher magnetic
moments, non-fouling surfaces, and increased
functionalities are now being developed for applications in
the detection, diagnosis, and treatment of malignant tumors,
cardiovascular disease, and neurological disease. Through
the incorporation of highly specific targeting agents and
other functional ligands, such as fluorophores and
permeation enhancers, the applicability and efficacy of
these MNPs have greatly increased. This review provides a
background on applications of MNPs as MR imaging
contrast agents and as carriers for drug delivery and an
overview of the recent developments in this area of
research.15
Resealed erythrocytes have various advantages as drug
carriers such as it is biodegradable, biocompatible, large
quantity of variety of material can be encapsulated within
small volume of cell and can be utilized for organ targeting
etc. Due to these advantages of resealed erythrocytes,
magnetic resealed erythrocytes came in to existence which
contains ferrofluides (magnetite) along with loaded drugs
within the cell. Magnetically responsive ibuprofen-loaded
erythrocytes were prepared and characterized in vitro. The
erythrocytes loaded with ibuprofen and magnetite
(ferrofluids) using the preswell technique18. The loaded cell
effectively responded to an external magnetic field. Various
process variables including drug concentration, magnetite
concentration, sonication of ferrofluids that could affect the
loading of drugs and magnetite were studied. The loaded
erythrocytes were characterized for in vitro drug efflux,
hemoglobin release, morphology osmotic fragility, in vitro
magnetic responsiveness and percent cell recovery. In the
continuous study, diclofenac sodium bearing erythrocytes
were prepared by preswell technique and characterized for
various in vitro parameters.19

The important properties of magnetic particles for medical

applications are nontoxicity, biocompatibility, injectability
and high-level accumulation in the target tissue or organ.
Magnetic nanoparticles modified with organic molecules
have been widely used for biotechnological and biomedical
applications as their properties can be magnetically
controlled by applying an external magnetic field16.
Furthermore, a novel application of magnetic nanoparticles
Fig 6 - Prevention of Arterial Thrombosis by Aspirin loaded
and magnetic forces for tissue engineering, termed
Magnetic Resealed Erythrocytes.
'magnetic force-based tissue engineering' has been
proposed. Particular attention had been paid to the Thrombosis absorbed or flushed due to the Force exerted
preparation methods that allow the synthesis of particles of by flow of Magnetic
nearly uniform size and shape.17 Erythrocytes under magnetic field, aspirin also released in
vicinity of thrombosis
(Thrombolytic effect)

Local thrombosis in animal arteries was prevented by

means of magnetic targeting of aspirin loaded red cell.
Thrombosis was induced in 18 dogs and 16 rabbit’s arteries
by surgically inverting a vascular wall flap into its lumen. A
completely occluding red thrombus was developed inside
the vessel after 4 to 5 hrs in 80% of cases. SmCo5 magnet
was secured externally to one of the arteries. The constant
magnetic field produced by the magnet had no influence on
the clot formation. Autologous red cells loaded with
ferromagnetic colloid compound and aspirin were
administered intravenously, and completely aborted
arteriothrombosis on magnet application side with no
deterioratory effect on clot formation in the control artery
Fig 5 -Schematic representation of retaining of Magnetic was recorded.20
nanoparticles at Rat Tail target segment
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 Research J. Pharm. and Tech. 4(11):Nov. 2011
E) Magnetic Emulsion:
Besides magnetic modulated systems, like
microcapsules/microspheres Magnetic emulsion was also
tried as drug carrier for chemotherapeutic agents. The
emulsion is magnetically responsive oil in water type of
emulsion bearing a chemotherapeutic agent which could be
selectively localized by applying an external magnetic field
to specific target site21.Akimoto and Morimoto prepared
magnetic emulsion by utilizing ethyl oleate based magnetic
fluid as the dispersed phase, casein solution as the
continuous phase and anticancer agent, methyl CCNU
trapped in the oily dispersed phase as active
chemotherapeutic agent. Magnetic emulsion appears to
have potential in conferring site specificity to certain
chemotherapeutic agent.22
F) Biomodulators:
Biological response modifiers (BMRs) alter host, tumor as
well as microbial responses in four ways23
1. Augmentation of host effectors mechanisms directed
against tumor cells or micro organisms.
2. Decrease in host response that interferes with tumor
resistance by a quantitative increase in endogenous effector
resistance by an increase in endogenous effector molecules
or redirecting their sites and duration of action.
3. Augmentation of tumor sensitivity to host cells by
dedifferentiating tumor cells.
4. Increase in host tolerance of conventional cancer
treatment.
There are basically two types of agents; Indirect and direct
agents. Indirect agents include white cell chemo attractant /
activator peptides, interleukins (1 to 4) and
immunomodulators such as interferon ( , , ). Direct
acting BMRs is the final lymphocytes effector molecules.
These are exemplified by antibodies, lymphotoxin and
tumor necrosis factor (TNF, also called as Cachetin).
G) Magnetic Neutrophils:
In certain clinical conditions, where patient sera contains
chemotactic factor in activators and neutrophils directed
inhibitors of chemotaxis , an indirect approach of targeting
white cells by chemo attraction fails. These disorders
include chronic lymphocytic leukemia, alcoholic cirrhosis,
Crohn’s disease, haemodialysis, sarcoidosis and Hodgkin’s
disease. Even though failure of chemotaxis is not observed
in all patients, such conditions are life threatening.
Therefore, a means of making neutrophils ingest magnetite
base system ought to be developed, so that the sites of
severe infection can be selectively approached for therapy24.
Applications of Magnetic systems:
Magnetic drug delivery system have many application in
various fields but out of these drug targeting utilizing
magnetic micro carriers is very important. Some of the
application of magnetically guided drug targeting especially
tumor targeting along with some other application utilizing
magnetic micro carriers has been summarized here25.
1653
Magnetic systems for the therapy of diseases:
Magnetic delivery of chemotherapeutic drugs to liver
tumours:-
The first clinical cancer therapy trial using Magnetic
microspheres (MMS) was performed by Lübbe in Germany
for the treatment of advanced solid cancer in 14 patients.
Their Magnetic microspheres were small, about 100 nm in
diameter, and filled with 4_-epidoxorubicin. The phase I
study clearly showed the low toxicity of the method and the
accumulation of the Magnetic microspheres in the target
area. However, MRI measurements indicated that more than
50% of the Magnetic microspheres had ended up in the
liver. This was likely due to the particles’ small size and
low magnetic susceptibility which limited the ability to hold
them at the target organ. The start up company FeRx in San
Diego developed irregularly shaped carbon-coated iron
particles of 0.5–5nm in diameter with very high magnetic
susceptibility and used them in a clinical phase I trial for the
treatment of inoperable liver cancer. They have treated 32
patients to date and are able to super-selectively (i.e. well
directed) infuse up to 60 mg of doxorubicin in 600 mg
Magnetic microspheres with no treatment-related toxicity.
The firm recently started a large phase I/II trial for the
treatment of hepatocellular carcinoma in China, Korea, and
the US. Current preclinical research is investigating the use
of magnetic particles loaded with different
chemotherapeutic drugs such as mitoxantrone, mitomycin
C, etoposide, paclitaxel or oxaliplate. In case of brain
tumors, the therapeutic ineffectiveness of chemotherapy is
mainly due to the impervious nature of the blood-brain
barrier (BBB), presence of drug resistance and lack of
tumor selectivity. Various novel biodegradable magnetic
drug carriers are synthesized and their targeting to brain
tumor is evaluated in vitro and in animal models. New
cationic magnetic amino dextran micro spheres (MADM)
have been synthesized. Its potentiality for drug targeting to
brain tumor was studied. This particle were retained in
brain tissue over a longer period of time. In one of such
examples magnetic doxorubicin in liposome, significant
anticancer effect in nude mice bearing colon cancer26.
Magnetic bioseparation:
Bioseparation is an important phenomenon for the success
of several biological processes. Therefore, prospective
bioseparation techniques are increasingly gaining
importance. Amongst the different bioseparation
techniques, magnetic separation is the most promising. The
development of magnetically responsive microspheres has
brought an additional driving force into play. Particles that
are bound to magnetic fluids can be used to remove cells
and molecules by applying magnetic fields and-in vivo-to
concentrate drugs at anatomical sites with restricted access.
These possibilities form the basis for well-established
biomedical applications in protein and cell separation.
Additional modifications of the magnetic particles with
monoclonal antibodies, lectins, peptides, or hormones make
these applications more efficient and also highly specific.
The isolation of various macro molecules such as enzymes,
enzyme inhibitors, DNA, RNA, antibodies and antigens etc.
 Research J. Pharm. and Tech. 4(11):Nov. 2011

from different sources including nutrient media,
fermentation broth, tissues extracts and body fluids, has
been done by using magnetic absorbents. In case of enzyme
separation, the appropriate affinity ligands are immobilized
on polymer coated magnetic carrier or magnetizable
particles. Immobilized protein A or protein G on silanized
magnetite and fine magneto tactic bacteria can be used for
isolation and purification of Ig G. Mono sized super
paramagnetic particles, Dyna beads, have been used in
isolation of mRNA, genomic DNA and proteins27.
Magnetically induced Hyperthermia for treatment of
cancer:
Heat treatment of organs or tissues, such that the
temperature is increased to 42–460C and the viability of
cancerous cells reduces, is known as hyperthermia. It is
based on the fact that tumor cells are more sensitive to
temperature than normal cells. In hyperthermia it is
essential to establish a heat delivery system, such that the
tumor cells are heated up or inactivated while the
surrounding tissues (normal) are unaffected.
a) Intracellular hyperthermia:
The alternative approach is to use fine particles as heat
mediators instead of needles or rods such that hyperthermia
becomes noninvasive. When fluids containing submicron-
sized magnetic particles (typically 1–100nm) are injected,
These particles are easily incorporated into the cells, since
their diameters are in the nanometer range. These magnetic
particles selectively heat up tissues by coupling AC
magnetic field to targeted magnetic nano particles. As a
result, the whole tumor can be heated up uniformly. This is
called intracellular hyperthermia. It has been shown that
malignant cells take up nine times more magnetic nano
particles than normal cells. Therefore the heat generated in
malignant cells is more than in normal cells. Also, as blood
supply in the cancerous tissues is not normal, the heat
dissipation is much slower. Hence, the temperature rise in
the region of tumor is higher than in the surrounding normal
tissues. It is therefore expected that this therapy is much
more concentrated and localized28.
effective than hyperthermia itself. The approach involves
use of magnetic carriers containing a drug to cause
hyperthermia using the standard procedure, followed by the
release of encapsulated drug that will act on the injured
cells. It is anticipated that the combined treatment might be
very efficient in treating solid tumor. Several reasons are
given for the enhanced effect. Tumors are poorly
vascularised and it can be hard for therapeutic agents to
reach their target. Heat increases the perfusion of a tumor
and therefore drugs are transported more effectively into the
target tissues. In addition, heat makes blood vessels more
permeable to drugs. This occurs preferentially in tumors
where blood vessels tend to be structurally incomplete. On
the other hand, normal blood vessels are surrounded by a
basement membrane and other perivascular cells and not
significantly affected by heat. It has recently been reported
that hyperthermia increases the rate of liposome leakage
into tumors by a factor of 2–5 depending on the type of
tumor. In normal tissues however, enhancement of
liposome leakage is not reported. The magnetic component
in microspheres can also be used for purposes other than
targeting. Langer et al. embedded magnetite or iron beads
into a drug-filled polymer matrix and then showed that they
could activator increase the release of the drug from the
polymer by moving a magnet over it or by applying an
oscillating magnetic field. The micro-movement within the
polymer seemed to have shaken the matrix or produced
“micro-cracks,” and thus made the influx of liquid,
dissolution and efflux of the drug possible. In this way, it
was possible to magnetically activate the release of insulin
from a depot underneath the skin. Done repeatedly, this
would allow for pulsatile drug delivery30.

b) Magnetic fluid hyperthermia (MFH):

Magnetic fluids can be defined as fluids, consisting of
ultramicroscopic particles. (~100Å) of magnetic oxide.
Magnetic fluid hyperthermia is based on the fact that sub
domain magnetic particles produce heat through various
kinds of energy losses during application of an external AC
magnetic field. If magnetic particles can be accumulated
only in the tumor tissue, cancer specific heating is available,
various biocompatible magnetic fluids. Cationic
magnetoliposomes and affinity magnetoliposomes have
been used for hyperthermia treatment29.

c) Combination therapy:
There also exists the combination therapy which would
induce hyperthermia treatment followed by chemotherapy Fig.7. Magnetic control of pharmacokinetic parameter rand
or gene therapy. A combination of chemotherapy or Improvement of Drug releases
radiation therapy with hyperthermia is found much more
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 Research J. Pharm. and Tech. 4(11):Nov. 2011
Magnetic targeting of radioactivity:
Magnetic targeting can also be used to deliver therapeutic
radioisotopes. The advantage of this method over external
beam therapy is that the dose can be increased, resulting in
improved tumor cell eradication, without harm to nearby
normal tissue. Different radioisotopes can treat different
treatment ranges depending on the radioisotope used—the
emitters 90Y for example will irradiate up to a range of
12mm in tissue. Unlike chemotherapeutic drugs, the
radioactivity is not released, but rather the entire radioactive
microsphere is delivered to and held at the target site to
irradiate the area within the specific treatment range of the
isotope. Once they are not radioactive anymore,
biodegradation of the microspheres occurs (and is desired).
Initial experiments in mice showed that intra peritoneally
injected radioactive poly lactic acid based MMS could be
concentrated near a subcutaneous tumor in the belly area,
above which a small magnet had been attached31. The dose-
dependent irradiation from the emitter 90Y-containing
MMS resulted in the complete disappearance of more than
half of the tumors. Magnetic targeted carriers (MTC; from
FeRx), which are more magnetically responsive iron carbon
particles, have been radio labelled in the last couple of years
with isotopes such as 188Re , 90Y, 111In and 125I and are
currently undergoing animal trials32.
Miscellaneous Applications:
The most important application of magnetic particles is as
contrast agent for magnetic resonance imaging in diagnosis
of diseases. The most commonly used super paramagnetic
material is Fe3O4 with different coatings such as dextrans,
polymers, and silicone. Supra magnetic iron oxide (SPIO) it
has been mainly used as a liver-specific contrast agent for
intravenous application. It may also be used for detection of
metastases in non-enlarged lymph nodes. Magnetic
elements have been successfully used in gastrointestinal
surgery for tissue fixation. Which form hermetic seal after
surgery and passibility of the gastrointestinal tract is
maintained and the patient can able to eat immediately after
operation. Magnetically guided ferro fluid nanoparticles
were used in retinal repair. Magnetically guided interstitial
diffusion of the nanoparticles up to 20mm of the gel over
periods of 72 hours was shown to be possible, thus
demonstrating that essentially all points on the retinal
surfaces are reachable from elsewhere in the ocular interior.
Apart from their application in drug delivery, magnetism
have sound applications in biosciences and biotechnologies
like immobilization, detection of biologically active
compound and xenobiotic, detection, isolation and study of
cells and cells organelles. Similar to chemotherapeutic
drugs, many other drugs including peptides and proteins can
be adsorbed or encapsulated into magnetic microspheres or
nanospheres. Normal pharmaceutical technology is
employed to influence release kinetics. Ongoing work
describes the encapsulation of the peptide octreotide and the
protein tumor necrosis factor alpha (TNF). A very recent
development in the field of magnetic targeting is the use of
magnetically enhanced gene therapy. Advantages of such an
1655
approach are targeted gene transfection at rapid speed and
high efficiencies. It is also possible to use only the
mechanical-physical properties of magnetic particles or
ferrofluids for therapy. One example is the embolization
(clogging) of capillaries under the influence of a magnetic
field. In this way, tumors could be specifically starved of
their blood supply. Another elegant example is the use of
magnetic fluids to prevent retinal detachment, thus
preventing the patients from going blind. A magnetized
scleral buckle, similar to a rubber band, is placed around the
eye. The magnetic fluid is then injected into the eye and
immediately drawn towards the buckle by its magnetic
forces33.
Magnetic systems for the diagnosis of diseases:
The most important diagnostic application of magnetic
nanospheres is as contrast agents for magnetic resonance
imaging (MRI). Saini tested 0.5–1 _m sized ferrites in vivo
for the first time in 1987. Since then, smaller super
paramagnetic iron oxides (SPIOs) have been developed into
unimodular nanometer sizes and have since 1994 been
approved and used for the imaging of liver metastases
(ferumoxide based Feridex I.V., or Endorem in Europe) or
to distinguish loops of the bowel from other abdominal
structures (GastroMark, or Lumirem in Europe) 34.
Magnetic systems for magnetic cell separation:
The era of using magnetic particles with surface markers
against cell receptors started in 1978. Currently, many
different kits for the sample preparation, extraction,
enrichment and analysis of entire cells based on surface
receptors, and subcellular/molecular components such as
proteins, mRNA, DNA are available. Analytical
procedures, such as many different immunoassays, are often
based on magnetic separation. More information is
available from the firms providing these kits, such as Dynal,
Miltenyi, Bangs Laboratories, micromod. One important
application of magnetic cell separation is the purging of
malignant cells from auto logous stem cell products,
depletion of T cells, and selection of specific lymphocyte
subsets with potential antileukemic activity. In this way, a
cancer patient’s stem cells can be extracted, purified, and
then injected again after he has gone through a harsh
cancer. The therapeutic applications of immune magnetic
cell selection are based on antibodies that bind to cancer
cell antigens such as CD10, CD19 or CD20. Two machines
for magnetic cell separation have recently received FDA
approval, Cellpro’s “Ceprate SC stem cell collection
system” and Baxter’s “Isolex 300I.” A third system is
approved in Europe, Miltenyi’s “ClinicMACS” system35.
Magnetic Systems in Contraceptive Drug Delivery
In these magnetically controlled systems, the drug and
small magnetic beads are uniformly dispersed within a
polymer material. On exposure to aqueous media, the drug
is released in a diffusion controlled fashion. Moreover, the
rate can be increased or modulated on application of an
oscillating external magnetic field (Robinson and Lee,
1987). These system may be useful when drug delivery is
 Research J. Pharm. and Tech. 4(11):Nov. 2011

designed responsive to the changes in steroid secretion of implanted devices. However, utility of such implants has
during the menstrual cycle36. been compromised due to irreproducibility of magnetic
modulation and necessity of surgery to replace such
Future Perspectives:- implants after complete drug release. Externally
Conceptually, magnetic targeting is a very promising programmable infusion pump, need magnetic modulation
approach. However, there are a number of physical, only to a limited extent for activating radiometry circuits to
magnetism-related properties which require careful allow bi-directional information transfer. These pumps are
attention. First, the magnetic force, which is defined by its potentially useful and exhibit the flexibility required in the
field and field gradient, needs to be large and carefully complex clinical applications of the forthcoming future.
shaped to fit the target area. For in vivo applications, this is
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