Journal of Magnetism and Magnetic Materials 379 (2015) 102–107

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Journal of Magnetism and Magnetic Materials

journal homepage: www.elsevier.com/locate/jmmm

Mathematical modelling for trajectories of magnetic nanoparticles in a

blood vessel under magnetic field
Shashi Sharma n, V.K. Katiyar, Uaday Singh
Department of Mathematics, Indian Institute of Technology, Roorkee 247667, India

art ic l e i nf o a b s t r a c t

Article history: A mathematical model is developed to describe the trajectories of a cluster of magnetic nanoparticles in a
Received 16 September 2014 blood vessel for the application of magnetic drug targeting (MDT). The magnetic nanoparticles are in-
Received in revised form jected into a blood vessel upstream from a malignant tissue and are captured at the tumour site with
8 December 2014
help of an applied magnetic field. The applied field is produced by a rare earth cylindrical magnet po-
Accepted 11 December 2014
Available online 13 December 2014
sitioned outside the body. All forces expected to significantly affect the transport of nanoparticles were
incorporated, including magnetization force, drag force and buoyancy force. The results show that par-
Keywords: ticles are slow down and captured under the influence of magnetic force, which is responsible to attract
Magnetic nanoparticles the magnetic particles towards the magnet. It is optimized that all particles are captured either before or
Magnetic drug targeting
at the centre of the magnet (z r 0) when blood vessel is very close proximity to the magnet (d¼ 2.5 cm).
Particle trajectory
However, as the distance between blood vessel and magnet (d) increases (above 4.5 cm), the magnetic
nanoparticles particles become free and they flow away down the blood vessel. Further, the present
model results are validated by the simulations performed using the finite element based COMSOL
software.
& 2014 Elsevier B.V. All rights reserved.

1. Introduction [16]. A detail discussion on the current and future prospective of

The delivery of anticancer agents to the specific target sites
with minimum side effects is an important challenge in chemo,
radio and gene-therapy. Magnetic Drug Targeting (MDT) is one of
the promising methods for effective targeting and delivery of
drugs to a specific target with aid of a local magnetic field [1,2]. In
this method, magnetic carrier particles loaded with drug mole-
cules are injected into the microvasculature upstream from the
malignant tissue and attracted towards the targeted region in the
body with help of a local magnetic field [3–6]. MDT is growing due
to speedy progress in the growth of functionalized magnetic na-
noparticles, which are used for chemo, radio, and gene-therapy at
a tumour site [7,8]. It is also shown by various studies that MDT is
relatively safe and effective method for targeting drugs to a spe-
cific site [9–11].
Previous work on magnetic particles transport in the vascu-
lature for MDT is summarized in many review papers [12–14].
Kingsley et al. [15] examined the development of nanoparticles
based targeted drug delivery systems in detail. The magnetite
(Fe3O4) nanoparticles are generally used in targeted drug delivery
systems because of their biocompatibility and large magnetization
n
Corresponding author. Fax: þ91 1332 273560.
E-mail address: shashisharma1984@gmail.com (S. Sharma).
the targeted drug targeting through the blood stream by magnetic
drug carriers was presented by Yokoyama [17]. Lubbe et al. [10]
also elaborated the details of the usage of magnetic nanoparticles
as a carrier in medical applications through a review article. A
two-dimensional mathematical model for magnetic particle
transport as a drug carrier has been developed by Aviles et al. [18]
at the carotid bifurcation region. Shaw et al. [19] presented a
model to achieve high concentration of drug at the targeted region
in the impermeable micro-vessel by assuming blood as Herschel–
Bulkley fluid. Ritter et al. [20] studied the targeted of drug by the
magnetic carrier at a specific site by employing high gradient
magnetic separation technique using FEMLAB simulations. Rotariu
and Strachan [21] evaluated the targeting of magnetic nano-
particles at the tumour site located deep inside the body through
computational simulations. Furlani and Furlani [22] presented an
analytic model for transport and capture of therapeutic magnetic
nanoparticles in the human microvasculature for targeted drug
delivery applications. Design of an effective MDT system requires
research in three main areas: synthesis of composite drug and
magnetic particles, real-time imaging of magnetic particles as they
move through the blood stream, and development of technology
to steer the particles through the circulatory system and hold
them at the correct location [23]. The current work focuses on the
second and third area of research in the field of magnetic drug
targeting.

http://dx.doi.org/10.1016/j.jmmm.2014.12.012
0304-8853/& 2014 Elsevier B.V. All rights reserved.
 S. Sharma et al. / Journal of Magnetism and Magnetic Materials 379 (2015) 102–107 103

In the present work, a mathematical model is developed to considering the gravitational force, respectively. Furthermore, we
describe the trajectories of a cluster of magnetic nanoparticles in a have not included Brownian motion because it is negligible when
blood vessel with the aid of a local magnetic field applied through particles are very small. The magnetic, fluidic and buoyancy forces
a cylindrical magnet positioned outside the body. The magnetic experienced by the carrier particles in the blood vessel under the
nanoparticles are flowing along the axis of blood vessel and influence of external magnetic field are calculated as given below.
magnetic field is applied perpendicular to the direction of the
blood flow. The mathematical equations used in the model are 2.1.1. Magnetic force
solved using classical fourth order Runge–Kutta method to predict If the magnetic particles are suspended in a fluid with per-
the magnetic particle trajectories within a blood vessel. The model meability μ f , the force experienced by the magnetic particles in an
is also used to optimize the position of outside magnet for mag- applied field H is [22] given as below,
netic particle capture at the tumour site for effective drug
targeting. 3χp
Fm = μ 0 Vp (H⋅∇) H
(χp + 3) (4)
2. Description and mathematical formulation 4
where Vp = 3
πR p3
is the volume of the particle and χp is the sus-
ceptibility of the particle. H is the externally applied magnetic
The present model is developed to predict the transport and
field.
capture of magnetic nanoparticles under the influence of magnetic
Here, μ0 = 4π × 10−7 H /m is the permeability of free space.
field. The magnetic nanoparticles are injected into the blood vessel
We consider the motion in x–z plane and therefore, the mag-
and their flow within blood (in the direction of z axis along the
axis of blood vessel) is targeted by applying an external magnetic netic force can be expressed as
field. The magnetic field is applied by a rare-earth cylindrical Fm = Fmx^
x + Fmz ^
z
magnet positioned outside the body. The magnet is assumed to be
infinite extent and oriented to the perpendicular direction of the The magnetic force can be decomposed into its components
blood flow (x direction). The schematic diagram of magnetic par- form as
ticle transport in a blood vessel is depicted in Fig. 1. The blood
3χp⎡ ∂Hx (x, z) ∂Hx (x, z) ⎤
vessel is assumed to be a cylindrical tube with laminar flow of Fmx (x, z) = μ 0 Vp ⎢Hx (x, z) + Hz (x, z) ⎥
⎣ ⎦
magnetic particles within blood parallel to its axis. (
χp + 3 ) ∂ x ∂z
(5)

2.1. Mathematical formulation and

3χp ⎡ ∂Hz (x, z) ∂Hz (x, z) ⎤
The transport of magnetic nanoparticles in the vascular system Fmz (x, z) = μ 0 Vp ⎢Hx (x, z) + Hz (x, z) ⎥
is governed by a number of forces [24], however, in the present χp + 3 ⎣
( ) ∂x ∂z ⎦
(6)
study, we considered the dominant magnetic, drag and buoyancy
forces and a steady flow analysis is implemented. where H (x, z) = Hx (x, z) ^
x + Hz (x, z) ^
z
The motion of nanoparticles is governed by using the Newton's The components of magnetic field for an infinite cylindrical
second law magnet, which is magnetized perpendicular to its axis, can be
d vp represented inside the blood vessel as below [22].
mp = ∑ Fext (1) Here,
dt
2 ⎡ 2 2⎤
⎣ (x + d) − z ⎦
where m p and vp are the mass and velocity of the magnetic particle Ms R m
Hx (x, z) =
and ∑ Fext represents all the external forces exerted on the particle. 2 ⎡ (x + d)2 + z 2⎤2
d vp ⎣ ⎦ (7)
The inertial term m p dt is very small, and could be ignored.
Then Eq. (1) becomes and
2
∑ Fext = 0 (2) Ms R m 2(x + d) z
Hz (x, z) =
2 ⎡ (x + d)2 + z 2⎤2
and ⎣ ⎦ (8)

∑ Fext = Fm + F f + Fb (3) Here, Ms , Rm and d are the magnetization of the magnet, radius
of the magnet and distance of magnetic nanoparticles from the
where Fm ,F f and Fb are the magnetic, fluidic and buoyancy force centre of the magnet.
The partial derivatives of above these components of magnetic
field w.r.t. x and z can be evaluated as

∂Hx (x, z) (x + d) ⎡⎣ (x + d)2 − 3z 2⎤⎦

2
= − Ms R m
∂x ⎡ (x + d)2 + z 2⎤3
⎣ ⎦ (9a)

z ⎡3(x + d)2 − z 2⎤⎦

∂Hx (x, z) 2 ⎣
= − Ms R m
∂z ⎡ (x + d)2 + z 2⎤3
⎣ ⎦ (9b)

z ⎡z 2 − 3(x + d)2⎤⎦
Fig. 1. Schematic diagram of the magnetic nanoparticles transport in a blood
∂Hz (x, z) 2 ⎣
= Ms R m
vessel. The cylindrical magnet is positioned outside the vessel to apply the mag- ∂x ⎡ (x + d)2 + z 2⎤3
⎣ ⎦ (9c)
netic field.
104 S. Sharma et al. / Journal of Magnetism and Magnetic Materials 379 (2015) 102–107

∂Hz (x, z) (x + d) ⎡⎣ (x + d)2 − 3z 2⎤⎦ 2.1.4. Equations of motion

2
= Ms R m We have the velocity components of the magnetic particles in x
∂z ⎡ (x + d)2 + z 2⎤3
⎣ ⎦ (9d) and z direction by putting Eqs. (10), (11), (17), (18) and (19) in Eq.
(2). The equation of motion for particle travelling along the axis of
Using Eqs. (7), (8) and (9), we can simplified the Eqs. (5) and (6) blood vessel can be written as
as
dx 1 d 2 2
vp, x = = μ 0 R p2 Ms2 R m4 − R p (ρp − ρ f ) g
3μ 0 Vp χp Ms2 R m4 (x + d) dt 3η (d2 + z 2)3 9η (20)
Fmx (x, z) =
(χp + 3) 2 ⎡⎣ (x + d)2 + z 2⎤
3
⎦ (10) and
⎡ ⎛ x ⎞2⎤
dz 1 z
3μ 0 Vp χp Ms2 R m4 z vp, z = = μ 0 R p2 Ms2 R m4 + 2v¯ f ⎢1 − ⎜ ⎟ ⎥
Fmz (x, z) = dt 3η (d2 + z 2)3 ⎢⎣ ⎝ R v ⎠ ⎥⎦ (21)
( ) 2 ⎡⎣ (x + d)2 + z 2⎤⎦
3
χp + 3
(11)
The Eqs. (20) and (21) are coupled and solved numerically
We consider that x/d⪡1, means the distance from the magnet to using classical fourth order Runge–Kutta method to predict the
the blood vessel is much larger than the diameter of the blood trajectories of magnetic particles in radial and axial directions.
vessel itself and χp ⪢1. In the present model, the iron oxide (Fe3O4) particles of radius
Based upon these assumptions, the magnetic force components (R p = 300 nm ) are taken into account as magnetic nanoparticles
reduces to with density ρp = 5000 kg/m3 to study their transport in a blood
vessel under magnetic field. It is assumed that the magnetic sus-
d ceptibility of Fe3O4 particles is very large in comparison to 1
Fmx (x, z) = 3μ 0 Vp Ms2 R m4
2[d2 + z 2]3 (12) ( χp ⪢1). Further a rare earth NdFeB cylindrical magnet was used to
apply the magnetic field positioned outside the body. The dia-
and
meter of magnet is 4 cm (Rm = 2 cm ) and its saturation magneti-
z zation is 106 A/m. The magnet is positioned at 2.5, 3.5, 4.5, 5.5 and
Fmz (x, z) = 3μ 0 Vp Ms2 R m4
2[d2 + z 2]3 (13) 6.5 cm from the centre of axis of blood vessel to the centre of
magnet to study their effect on particle trajectories. The radius of
blood vessel (R v ) is selected 75 μm and average flow velocity (v¯ f ) is
2.1.2. Fluidic force 10 mm/s. The viscosity (η) and density ( ρ f ) of the blood is assumed
The fluidic force on the magnetic particles is given by to be 3.2  10  3 N s/m2 and 1060 kg/m3, respectively.
F f = − 6πηR p (vp − v f ) (14)

where vp and v f are the velocity of particle and fluid respectively. η 3. Results and discussion
and R p are the viscosity of blood and radius of the magnetic par-
ticles, respectively. Fig. 2 shows the calculated vertical and horizontal components
We assume that the blood vessel is cylindrical and blood flow is of the magnetic field (Hx and Hz ) along the axis of blood vessel. The
fully laminar parallel to the axis. On the basis of these assump- magnetic field components (Hx and Hz ) along the axis of blood
tions, the blood velocity is given by vessel (−3Rm ≤ z ≤ 3Rm ) are calculated using the Eqs. (7 and 8) for
d¼ 2.5 cm. It can be observed through Fig. 2 that Hx obtains the
⎡ ⎛ x ⎞2⎤ maximum value (4000 Gauss) at the centre of magnet (z /Rm = 0),
v f (x) = 2v¯ f ⎢1 − ⎜ ⎟ ⎥ whereas Hz oscillates around the central axis of blood vessel and
⎢⎣ ⎝ R v ⎠ ⎥⎦ (15) shows the peaks towards the edges of magnet (z /Rm = ± 1) that
changes their direction from one edge to the other.
We consider the motion in x–z plane and therefore, the fluidic
The vertical and horizontal components of the magnetic force
force can be expressed as
(Fmx and Fmz ) along the axis of blood vessel (−3Rm ≤ z ≤ 3Rm ) are
F f = F fx ^
x + F fz ^
z (16)

The fluidic or drag force can be decomposed into its compo-

nents form as

F fx = − 6πηR p vp, x (17)

⎛ ⎛ ⎛ x ⎞2⎞ ⎞
F fz = − 6πηR p ⎜vp, z − 2v¯ f ⎜⎜1 − ⎜ ⎟ ⎟⎟ ⎟
⎜ ⎝ R v ⎠ ⎠ ⎟⎠
⎝ ⎝ (18)

2.1.3. Buoyancy force

Buoyancy force considering the gravitational force in a viscous
fluid is given by
^
Fb = − Vp (ρp − ρ f ) g x (19)

where ρp and ρ f are the particle and fluid density, respectively and
Fig. 2. The vertical (Hx) and horizontal component (Hz) of the magnetic field along
g = 9.8 m /s2 is the acceleration due to gravity. the axis of blood vessel.
 S. Sharma et al. / Journal of Magnetism and Magnetic Materials 379 (2015) 102–107
Fig. 3. The vertical (Fmx) and horizontal component (Fmz) of the magnetic force
along the axis of blood vessel.
shown in Fig. 3. The magnetic force components (Fmx and Fmz )
along the axis of blood vessel are calculated using the Eqs. (12 and
13). It is observed that horizontal component of the magnetic force
(Fmz ) shows similar profile as the magnetic field counterpart (Hz )
with reverse direction. Therefore, Fmz oscillates around the central
axis of blood vessel and shows the maximum value towards the
edges of magnet (z /Rm = ± 1). Consequently, as a magnetic particle
travels horizontally above the magnet from left to right, it ex-
periences a horizontal acceleration as it passes through the leading
edge of magnet. However, deceleration is experienced as it passes
through the trailing edge. As a result, horizontal component of the
magnetic force (Fmz ) is responsible for the oscillatory movement of
nanoparticles within the blood vessel. Moreover, the vertical
component of magnetic force (Fmx ) is strongest at the centre of the
magnet (z /Rm = 0) and its strength decreases as towards edges of
the magnet (z /Rm = ± 1). The value of Fmx is 0.20 pN at the centre of
magnet. This force is attractive in nature and responsible to attract
or capture the magnetic particles towards the magnet.
The trajectories of magnetic particles flowing in a blood vessel
at various positions are calculated using the Eqs. (20 and 21)
and shown in Fig. 4. The trajectories are presented for a range of
initial positions along the x axis from x ¼ 0.8Rv,  0.6Rv,  0.4Rv,
0.2Rv, 0, 0.2Rv, 0.4Rv, 0.6Rv, 0.8Rv and 1.0Rv. The particles are
assumed to be of radius 300 nm. The blood vessel is selected as a
cylindrical tube of diameter 75 μm and an average flow velocity is
10 mm/s. The magnet is placed close to blood vessel with a
distance of 2.5 cm. In these curves, the radial position (x) of
magnetic particles is normalized with respect to the radius of
blood vessel (R v ) and axial position (z) is normalized with respect
Fig. 4. Trajectories of magnetic nanoparticles in a blood vessel at various positions
for d ¼ 2.5 cm.
105
Fig. 5. Variation in vertical component of magnetic field (Hx) and force (Fmx) at
different d values.
to the radius of magnet (Rm ). It is observed that all particles are
captured either before or at the centre of the magnet (e.g. z r0)
when the distance between blood vessel and magnet (d) is 2.5 cm
and vertical component of magnetic field (Hx ) is around
4000 Gauss (as shown in Fig. 2). The particles flowing near the
lower surface of the blood vessel (x¼  0.8Rv) starts to capture first
near the leading edge of magnet and all the particle including
closer to the upper surface of blood vessel are captured up to the
centre of magnet (z /Rm = 0). The early capture of lower surface
magnetic particles is due to large magnetic force experienced by
these particles because of close proximity with the magnet.
The variation in vertical component of magnetic field (Hx ) and
magnetic force (Fmx ) with respect to distance between blood vessel
and magnet (d) is shown in Fig. 5. It is observed that the vertical
component of magnetic field as well as magnetic force is high near
the magnet and decreases as we increase the distance between
blood vessel and magnet (d). The vertical component of magnetic
field (Hx ) and magnetic force (Fmx ) is calculated at the centre of
blood vessel (x ¼z ¼0) using the Eqs. (7 and 12). Fig. 5 shows that
Hx decreases from 4000 to 330 Gauss and Fmx from 0.20 to
0.001 pN as we increase the distance between blood vessel and
magnet (d) from 2 to 7 cm, respectively.
The effect of distance (d) between magnet and blood vessel on
particle trajectories is shown in Fig. 6. It is noticed by this curve
that all particles at the centre of blood vessel are captured by the
magnet when the distance between the centres of the blood vessel
and the magnet is up to 4.5 cm. The magnetic field strength at
4.5 cm is 790 Gauss (Fig. 5). Further increase in the value of d to
5.5 and 6.5 cm, particles become free under the influence of
Fig. 6. Trajectories of magnetic nanoparticles flowing at the centre of blood vessel
at different d values ranging from 2.5 to 6.5 cm.
106 S. Sharma et al. / Journal of Magnetism and Magnetic Materials 379 (2015) 102–107
Fig. 7. Simulated trajectories of magnetic nanoparticles at different d values: (a) d ¼2.5, (b) d ¼3.5, (c) d ¼4.5 and (d) d¼ 5.5 cm.
attractive magnetic force (Fmx ) and they flow away down the blood
vessel. This is because the strength of magnetic force (Fmx ) is
proportional to the distance between blood vessel and magnet as
shown in Fig. 5. As the distance (d) increases, the vertical com-
ponent of magnetic force (Fmx ), which is responsible for capturing
the magnetic particles, decreases and results the free movement of
magnetic particles due to weak strength of attractive magnetic
force. So, it is optimized by this study that the distance between
magnet and blood vessel should be kept maximum up to 4.5 cm
(field strength  790 Gauss) to capture the magnetic particles to-
wards the magnet.
Further, the trajectories of magnetic nanoparticles are pre-
dicted using the particle tracing module of finite element based
COMSOL software. The dominant magnetic and fluidic drag forces
are considered to predict the transport of magnetic nanoparticles
in a cylindrical tube. Moreover, the diameter of tube, radius of
particle and strength of magnet are taken same as included in the
above model. The meshing around the geometry was 10 μm to
obtain precise trajectories of magnetic nanoparticles. The trajec-
tories of magnetic nanoparticles at different distances of cylind-
rical magnet from blood vessel ranging from 2.5 to 5.5 cm are
shown in Fig. 7. It can be noticed through Fig. 7 that all particles
are captured before or at the centre of magnet when the magnet is
in close proximity of blood vessel (d ¼ 2.5 cm). Further, as d value
increases to 3.5 cm, the magnetic particles are captured partially
and some particles flow away from the magnet in a laminar
fashion. Further enhancement in the distance of magnet to the
blood vessel (d ¼4.5 cm) results more particles free under the in-
fluence of magnet. Most of the particle become free and move in a
laminar style as the d value increases to 5.5 cm. The results in-
dicate that the distance between blood vessel and magnet is an
important parameter to capture the magnetic particles towards
the magnet. As the distance between magnet and blood vessel
increases the less number of particles captured. This is due to the
fact that magnetic force (Fmx ), which is responsible for capturing
the magnetic particles, decreases with d (as shown in Fig. 5) and
results the free movement of magnetic particles. Results obtained
through COMSOL software support our model results and conse-
quently validate our model.
4. Conclusions
In summary, a mathematical model is developed to predict the
trajectories of a cluster of magnetic nanoparticles in a blood vessel
under the influence of a permanent magnet positioned outside the
body. All forces, including magnetization, drag and buoyancy ex-
pected to significantly affect the transport of nanoparticles are
incorporated. The results show that all particles are captured ei-
ther before or at the centre of the magnet (zr0) when magnet is
very close proximity to the blood vessel (d ¼2.5 cm). This is due to
the influence of strong magnetic force, experienced by the mag-
netic particles, which is responsible to attract them towards the
magnet. It is optimized by this study that magnetic particles are
captured up to the 4.5 cm distance (d) between the blood vessel
and magnet. Further increase in d value (above 4.5 cm) results the
free movement of magnetic particles. In addition, the present
model results are validated through simulations performed using
COMSOL software.
Acknowledgements
One of the authors Ms. Shashi Sharma is thankful to Ministry of
Human Resource Development (M.H.R.D.), Govt. of India for re-
search fellowship. Authors are also thankful to Head, Department
of Physics, NIT Kurukshetra to allow using COMSOL software.
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