- Email: [email protected]
In vitro study of deep capture of paramagnetic particle for targeting therapeutics
ARTICLE IN PRESS Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
Contents lists available at ScienceDirect
Journal of Magnetism and Magnetic Materials journal homepage: www.elsevier.com/locate/jmmm
In vitro study of deep capture of paramagnetic particle for targeting therapeutics Ning Pei a,, Zheyong Huang b, Wenli Ma c, Junbo Ge b, Wenling Zheng c a
College of Science, Shanghai University, 99 Shangda Road, 200444 Shanghai, China Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 200032 Shanghai, China c South Genomics Research Center, South Medical University, 88 Tiangui Boulevard, 510800 Guangzhou, China b
a r t i c l e in fo
abstract
Article history: Received 24 October 2008 Available online 22 April 2009
Magnetic targeting, a promising therapeutic strategy for localizing systemically delivered drug to target tissue, is limited by magnetic attenuation. To satisfy the need of deep magnetic targeting, a special apparatus in which the magnetic flux density can be focused at a distance from the pole was designed. To test the aggregation property of this apparatus, we observed the accumulation of 500-nm paramagnetic particles as flowing through a tube served as a model of blood vessels. The relationship of the accumulation of the paramagnetic particles, the magnetic flux density, the magnetic field gradient and the fluid velocity was studied by theoretical considerations. & 2009 Elsevier B.V. All rights reserved.
PACS: 87.90.+y Keywords: Magnetic drug targeting Paramagnetic particle In vitro Magnetic flux density
1. Introduction Magnetic drug targeting (MDT) is a promising strategy for achieving localized drug delivery to tumor tissue [1–7]. Compared with traditional chemotherapy, the accumulation and retention of the magnetic drug carrier particles can be enhanced by using an external magnetic field, which is focused on the area of the tumor. Furthermore, MDT improves the effectiveness of the treatment by reducing the total dose needed to reach the therapeutic benefit, exposure of healthy tissue to the treatment and side effects [8,9]. In recent studies the magnet or general electromagnet [10–13] has been used to produce the magnetic field, which has some inherent limitations for the magnetic flux density is maximal at the magnet pole face and cannot be focused at a distance from the magnet [14]. Therefore, the application of the magnetic drug targeting has been limited to the superficial tumor, such as cutaneous carcinoma, mammary cancer. For treating deeper tumor, invasive approach, as implant assisted MDT, has been developed to implant wires, stents, magnetic particles as seeds or magnet at the target site to help attract and retain the magnetic drug carrier particles [15,16]. However, the cost and risk of surgery encumbers the wide clinical application. To overcome these limitations, a special self-made apparatus to produce the magnetic field which can be focused at a distance from the magnet was designed. To test the aggregation property of Corresponding author. Tel.: +86 21 66135082; fax: +86 21 66134208.
E-mail address: [email protected] (N. Pei). 0304-8853/$ - see front matter & 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2009.04.041
this apparatus, the accumulation of 500-nm paramagnetic particles was observed while the particles flowed through a tube served as a model of blood vessels under the different magnetic flux densities, magnetic field gradients and flow rates. The relationship of the accumulation of the paramagnetic particles, the magnetic flux density, the magnetic field gradient and the flow rate was studied by theoretical considerations.
2. Method 2.1. Experimental apparatus The experimental apparatus is shown in Fig. 1. The magnetic pole with the coil was cylindrical with hole in the middle. When current was through the coil, the magnetic field is z-axial symmetry in the cylindrical space between the poles. Thin quartz tube of an internal diameter of 4 mm was positioned vertically through the hole of the magnetic poles. The suspension of 500-nm paramagnetic particles was supplied by a 50 ml syringe. The flow rates were controlled by a syringe pump. The magnetic field was measured using a model 51,662 Leybold Tesla meter. 2.2. Experimental procedure The total 10 ml ethanol particle suspension, at a concentration of 0.01 mg Fe/ml, was placed in the syringe at each time. The
ARTICLE IN PRESS 2912
N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
The magnetic flux density of common electromagnet is maximal at the magnet pole face and decreases remarkably at a
distance from the magnet. In this paper, the magnetic pole with the coil was made of cylindrical iron with hole in the middle. When current was through the coil, the magnetic field was z-axial rotational symmetry in the cylindrical space (B-C) between the poles. Fig. 2 shows the flux tubes in the air gap between the poles with hole and without hole. Due to the fringing effects, there were more flux tubes, G2 and G3, in the air gap of the poles with hole than that without hole. So the magnetic field was focused at the center of the air gap and reduced dramatically along the z-axis. Because of the shield of magnetic poles, the magnetic flux density in the hole of the poles (A-B and C-D) was so minute that it could be neglected. Therefore, the magnetic flux density is maximal at the O site along the tube of A-D as shown in Fig. 3, which is the magnetic flux density distribution of the poles with hole calculated by finite-element analysis. And the test result was also consistent with it. Fig. 4 showed the dependence of the magnetic flux density measured by Tesla meter on z when r was 0 mm, the current in the
Fig. 1. Experimental apparatus and the system of coordinates.
Fig. 3. Flux density (magnitude) plot in hole of the magnetic poles.
optical microscopy images of the tubing segment located at O site were acquired after all the 10 ml particle suspension flowed through the tube. To study the effect of the magnetic field density and gradient on the accumulation of the paramagnetic particles, the magnetic field densities (B) were varied from 218 to 640 mT, corresponding to the magnetic field gradients (qB/qz) of 12–38.4 T/m, while keeping the same fluid velocity of 0.8 mm/s. Then to study the effect of the fluid velocity on the accumulation of the paramagnetic particles, keeping the same magnetic flux density of 720 mT, corresponding to the magnetic field gradient of 48 T/m, the fluid velocities were varied from 0.8 to 2.6 mm/s.
3. Results and discussion
Fig. 2. Flux tubes at the air gap: (a) poles without hole and (b) poles with hole in the middle.
ARTICLE IN PRESS N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
2913
Fig. 6. Paramagnetic particles aggregated at the O site far from the face of the poles.
Fig. 4. B–z relation of the apparatus.
Fig. 5. B-current and qB/qz-current relations at O site.
coil was 5 A and the distance between the pole faces was 10 mm. It can be seen the maximum of the magnetic flux density was located at O site. The magnetic flux density B at O site could vary from 0 to 800 mT and the magnetic gradient from 0 to 48 T/m with the current as shown in Fig. 5. When the paramagnetic particles went through from A to D, the magnetic attraction force on the particles was approximately zero in the route of A-B and C-D and increased to the maximal at the O site in the route of B-O, then decreased dramatically in
the route of O-C. The paramagnetic particles would be attracted and aggregate at the O site far from the face of the poles by the magnetic field when the paramagnetic particle suspension flowed through the tube as shown in Fig. 6. This means the instrument could make a deep accumulation of the paramagnetic particles. In future work, the animal could be placed in the hole of the pole and the deep tumor in the animal body could be located at O site to be treated by the magnetic drug targeting. The effect of the magnetic flux density B on the accumulation of the particles is shown in Fig. 7. In this study, a velocity of 0.8 mm/s, magnetic flux densities of 218, 407, 530, 640 and 0 mT (control experiments) were used. The effect of the magnetic field on the accumulation of the particles was very obvious. The accumulation of the particles increased when the magnetic field became stronger and the magnetic field gradient became bigger. Control experiments, done in the absence of an applied magnetic field, demonstrated minimal accumulation that could not be seen with the optical microscopy. The image analysis was used to quantify the accumulation of the particles. The plot shown in Fig. 8 illustrates the accumulation of particles for different magnetic flux densities and magnetic field gradients. The effect of the fluid velocity on the accumulation of the particles is shown in Fig. 9. In this study, the magnetic flux density of 720 mT, the magnetic field gradient of 48 T/m were used. To mimic conditions in microcirculation in animals, the fluid velocities were 0.8, 1.1, 1.6 and 2.6 mm/s, respectively. The results in Fig. 9 showed that the accumulation decreased with increasing velocity. The plot shown in Fig. 10 quantified this relationship. Magnetic capture of particles is governed mainly by two processes: magnetic attraction and hydrodynamic drag. Other forces such as floatage and gravity are ignored. The magnetic attraction force on the particles can be approximated by Fm ¼
1 wV p rðB2 Þ, 2 m0
(1)
where w is the particle’s magnetic susceptibility, Vp is the volume of the particle, m0 is the magnetic permeability of free space and B is the magnitude of the flux density.
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N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
Fig. 7. Images of samples at the same velocity of 0.8 mm/s, at different magnetic flux densities and magnetic field gradients (a) B ¼ 218 mT, qB/qz ¼ 12 T/m, (b) B ¼ 407 mT, qB/qz ¼ 23.4 T/m, (c) B ¼ 530 mT, qB/qz ¼ 30.6 T/m, (d) B ¼ 640 mT, qB/qz ¼ 38.4 T/m.
the particle, respectively. In the route of B-C, the magnetic attraction force on the particles increased and reached the maximal at the O site. The magnetic attraction force slowed the particles and changed the particle velocity in the z-direction. Consequently the increasing difference of velocity between particles and fluid liquid resulted in an increasing drag force. If the magnetic attraction was larger than the maximal drag force, the particles would be captured and accumulated at the center of the air gap. According to Eqs. (1) and (2), the magnetic attraction on a particle is proportional to the strength of the magnetic field and the field gradient that the particle experiences. Hence, the larger the magnetic flux density and the magnetic field gradient, the larger the magnetic force on a particle, the more accumulation was observed in the center of the air gap when the fluid velocity was same. Because the hydrodynamic force is proportional to the fluid velocity, the larger the fluid velocity, the larger the hydrodynamic force over a particle to be overcome to make the particle still, the less accumulation was observed in the center of the air gap.
4. Conclusions
Fig. 8. Effect of magnetic flux density and the magnetic field gradient on accumulation at the fluid velocity of 0.8 mm/s.
The hydrodynamic drag force (Fd) on the particle is given by Stokes’ law: F d ¼ 6pZRðv vp Þ
(2)
where Z is the medium viscosity, R is the magnetic particle’s radius and v and vp are the velocities of the bulk flow and
Due to special shape of poles, the magnetic field produced was stronger at the center of the air gap than any other place along the symmetrical axis. The magnetic field could aggregate the paramagnetic particles at a distance from the pole, making deep capture. Therefore, the apparatus was fit for the deep targeting. The experiment consisted of pumping a certain volume of the paramagnetic particles suspension through a tube positioned in the center of the poles. The effects of the magnetic flux density, magnetic field gradient and fluid velocity on accumulation of paramagnetic particles were investigated in vitro. The results demonstrated the accumulation of paramagnetic
ARTICLE IN PRESS N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
2915
Fig. 9. Images of samples at the magnetic flux density of 720 mT and the magnetic field gradient of 48 T/m and at different velocities of (a) 2.6 mm/s, (b) 1.6 mm/s, (c) 1.1 mm/s and (d) 0.8 mm/s.
Acknowledgments The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (Grant no. 50574056) and the Graduate Foundation of Shanghai University. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Fig. 10. Effect of fluid velocity on accumulation at the magnetic flux density of 720 mT and the magnetic field gradient of 48 T/m.
particles increased with increment in magnetic flux density and magnetic field gradient and decreased with increment in the fluid velocity.
Robert Langer, Science 293 (2001) 58. E.J. Furlani, E.P. Furlani, J. Magn. Magn. Mater. 312 (2007) 187. M.O. Avile´s, A.D. Ebner, J.A. Ritter, J. Magn. Magn. Mater. 320 (2008) 2640. M.O. Avile´s, A.D. Ebner, J.A. Ritter, J. Magn. Magn. Mater. 320 (2008) 2704. S. Dandamudi, R.B. Campbell, Biomaterials 28 (2007) 4673. X.Q. Yang, Y.H. Chen, R.X. Yuan, G.H. Chen, E. Blanco, J.M. Gao, X.T. Shuai, Polymer 49 (2008) 3477. X.L. Li, K.L. Yao, Z.L. Liu, J. Magn. Magn. Mater. 320 (2008) 1753. C. Alexiou, W. Arnold, R.J. Klein, F.G. Parak, P. Hulin, C. Bergemann, W. Erhardt, S. Wagenpfeil, A.S. Lu¨bbe, Cancer Res. 60 (2000) 6641. C. Alexiou, R.J. Schmid, R. Jurgons, M. Kremer, G. Wanner, C. Bergemann, E. Huenges, T. Nawroth, W. Arnold, F.G. Parak, Eur. Biophys. J. 35 (2006) 446. A.E. David, Y.Z. Huang, V.C. Yang, J. Control. Release 122 (2007) 315. M.W. Wilson, R.K. Kerlan, N.A. Fidelman, A.P. Venook, J.M. Laberge, J. Koda, R.L. Gordon, Radiology 230 (2004) 287. N.J. Darton, B. Hallmark, et al., Nanomedicine 4 (2008) 19. C. Alexiou, R. Schmid, R. Jurgons, C. Bergemann, W. Arnold, F.G. Parak, J. Drug Target 11 (2003) 139. G.P. Hatch, R.E. Stelter, J. Magn. Magn. Mater. 225 (2001) 262. J.W. Zheng, J.M. Wang, T. Tang, G. Li, H.B. Cheng, S.Q. Zou, Chin.-Germ. J. Clin. Oncol. 5 (2006) 336. J.A. Ritter, A.D. Ebner, K.D. Daniel, K.L. Stewart, J. Magn. Magn. Mater. 280 (2004) 184.
Contents lists available at ScienceDirect
Journal of Magnetism and Magnetic Materials journal homepage: www.elsevier.com/locate/jmmm
In vitro study of deep capture of paramagnetic particle for targeting therapeutics Ning Pei a,, Zheyong Huang b, Wenli Ma c, Junbo Ge b, Wenling Zheng c a
College of Science, Shanghai University, 99 Shangda Road, 200444 Shanghai, China Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 200032 Shanghai, China c South Genomics Research Center, South Medical University, 88 Tiangui Boulevard, 510800 Guangzhou, China b
a r t i c l e in fo
abstract
Article history: Received 24 October 2008 Available online 22 April 2009
Magnetic targeting, a promising therapeutic strategy for localizing systemically delivered drug to target tissue, is limited by magnetic attenuation. To satisfy the need of deep magnetic targeting, a special apparatus in which the magnetic flux density can be focused at a distance from the pole was designed. To test the aggregation property of this apparatus, we observed the accumulation of 500-nm paramagnetic particles as flowing through a tube served as a model of blood vessels. The relationship of the accumulation of the paramagnetic particles, the magnetic flux density, the magnetic field gradient and the fluid velocity was studied by theoretical considerations. & 2009 Elsevier B.V. All rights reserved.
PACS: 87.90.+y Keywords: Magnetic drug targeting Paramagnetic particle In vitro Magnetic flux density
1. Introduction Magnetic drug targeting (MDT) is a promising strategy for achieving localized drug delivery to tumor tissue [1–7]. Compared with traditional chemotherapy, the accumulation and retention of the magnetic drug carrier particles can be enhanced by using an external magnetic field, which is focused on the area of the tumor. Furthermore, MDT improves the effectiveness of the treatment by reducing the total dose needed to reach the therapeutic benefit, exposure of healthy tissue to the treatment and side effects [8,9]. In recent studies the magnet or general electromagnet [10–13] has been used to produce the magnetic field, which has some inherent limitations for the magnetic flux density is maximal at the magnet pole face and cannot be focused at a distance from the magnet [14]. Therefore, the application of the magnetic drug targeting has been limited to the superficial tumor, such as cutaneous carcinoma, mammary cancer. For treating deeper tumor, invasive approach, as implant assisted MDT, has been developed to implant wires, stents, magnetic particles as seeds or magnet at the target site to help attract and retain the magnetic drug carrier particles [15,16]. However, the cost and risk of surgery encumbers the wide clinical application. To overcome these limitations, a special self-made apparatus to produce the magnetic field which can be focused at a distance from the magnet was designed. To test the aggregation property of Corresponding author. Tel.: +86 21 66135082; fax: +86 21 66134208.
E-mail address: [email protected] (N. Pei). 0304-8853/$ - see front matter & 2009 Elsevier B.V. All rights reserved. doi:10.1016/j.jmmm.2009.04.041
this apparatus, the accumulation of 500-nm paramagnetic particles was observed while the particles flowed through a tube served as a model of blood vessels under the different magnetic flux densities, magnetic field gradients and flow rates. The relationship of the accumulation of the paramagnetic particles, the magnetic flux density, the magnetic field gradient and the flow rate was studied by theoretical considerations.
2. Method 2.1. Experimental apparatus The experimental apparatus is shown in Fig. 1. The magnetic pole with the coil was cylindrical with hole in the middle. When current was through the coil, the magnetic field is z-axial symmetry in the cylindrical space between the poles. Thin quartz tube of an internal diameter of 4 mm was positioned vertically through the hole of the magnetic poles. The suspension of 500-nm paramagnetic particles was supplied by a 50 ml syringe. The flow rates were controlled by a syringe pump. The magnetic field was measured using a model 51,662 Leybold Tesla meter. 2.2. Experimental procedure The total 10 ml ethanol particle suspension, at a concentration of 0.01 mg Fe/ml, was placed in the syringe at each time. The
ARTICLE IN PRESS 2912
N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
The magnetic flux density of common electromagnet is maximal at the magnet pole face and decreases remarkably at a
distance from the magnet. In this paper, the magnetic pole with the coil was made of cylindrical iron with hole in the middle. When current was through the coil, the magnetic field was z-axial rotational symmetry in the cylindrical space (B-C) between the poles. Fig. 2 shows the flux tubes in the air gap between the poles with hole and without hole. Due to the fringing effects, there were more flux tubes, G2 and G3, in the air gap of the poles with hole than that without hole. So the magnetic field was focused at the center of the air gap and reduced dramatically along the z-axis. Because of the shield of magnetic poles, the magnetic flux density in the hole of the poles (A-B and C-D) was so minute that it could be neglected. Therefore, the magnetic flux density is maximal at the O site along the tube of A-D as shown in Fig. 3, which is the magnetic flux density distribution of the poles with hole calculated by finite-element analysis. And the test result was also consistent with it. Fig. 4 showed the dependence of the magnetic flux density measured by Tesla meter on z when r was 0 mm, the current in the
Fig. 1. Experimental apparatus and the system of coordinates.
Fig. 3. Flux density (magnitude) plot in hole of the magnetic poles.
optical microscopy images of the tubing segment located at O site were acquired after all the 10 ml particle suspension flowed through the tube. To study the effect of the magnetic field density and gradient on the accumulation of the paramagnetic particles, the magnetic field densities (B) were varied from 218 to 640 mT, corresponding to the magnetic field gradients (qB/qz) of 12–38.4 T/m, while keeping the same fluid velocity of 0.8 mm/s. Then to study the effect of the fluid velocity on the accumulation of the paramagnetic particles, keeping the same magnetic flux density of 720 mT, corresponding to the magnetic field gradient of 48 T/m, the fluid velocities were varied from 0.8 to 2.6 mm/s.
3. Results and discussion
Fig. 2. Flux tubes at the air gap: (a) poles without hole and (b) poles with hole in the middle.
ARTICLE IN PRESS N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
2913
Fig. 6. Paramagnetic particles aggregated at the O site far from the face of the poles.
Fig. 4. B–z relation of the apparatus.
Fig. 5. B-current and qB/qz-current relations at O site.
coil was 5 A and the distance between the pole faces was 10 mm. It can be seen the maximum of the magnetic flux density was located at O site. The magnetic flux density B at O site could vary from 0 to 800 mT and the magnetic gradient from 0 to 48 T/m with the current as shown in Fig. 5. When the paramagnetic particles went through from A to D, the magnetic attraction force on the particles was approximately zero in the route of A-B and C-D and increased to the maximal at the O site in the route of B-O, then decreased dramatically in
the route of O-C. The paramagnetic particles would be attracted and aggregate at the O site far from the face of the poles by the magnetic field when the paramagnetic particle suspension flowed through the tube as shown in Fig. 6. This means the instrument could make a deep accumulation of the paramagnetic particles. In future work, the animal could be placed in the hole of the pole and the deep tumor in the animal body could be located at O site to be treated by the magnetic drug targeting. The effect of the magnetic flux density B on the accumulation of the particles is shown in Fig. 7. In this study, a velocity of 0.8 mm/s, magnetic flux densities of 218, 407, 530, 640 and 0 mT (control experiments) were used. The effect of the magnetic field on the accumulation of the particles was very obvious. The accumulation of the particles increased when the magnetic field became stronger and the magnetic field gradient became bigger. Control experiments, done in the absence of an applied magnetic field, demonstrated minimal accumulation that could not be seen with the optical microscopy. The image analysis was used to quantify the accumulation of the particles. The plot shown in Fig. 8 illustrates the accumulation of particles for different magnetic flux densities and magnetic field gradients. The effect of the fluid velocity on the accumulation of the particles is shown in Fig. 9. In this study, the magnetic flux density of 720 mT, the magnetic field gradient of 48 T/m were used. To mimic conditions in microcirculation in animals, the fluid velocities were 0.8, 1.1, 1.6 and 2.6 mm/s, respectively. The results in Fig. 9 showed that the accumulation decreased with increasing velocity. The plot shown in Fig. 10 quantified this relationship. Magnetic capture of particles is governed mainly by two processes: magnetic attraction and hydrodynamic drag. Other forces such as floatage and gravity are ignored. The magnetic attraction force on the particles can be approximated by Fm ¼
1 wV p rðB2 Þ, 2 m0
(1)
where w is the particle’s magnetic susceptibility, Vp is the volume of the particle, m0 is the magnetic permeability of free space and B is the magnitude of the flux density.
ARTICLE IN PRESS 2914
N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
Fig. 7. Images of samples at the same velocity of 0.8 mm/s, at different magnetic flux densities and magnetic field gradients (a) B ¼ 218 mT, qB/qz ¼ 12 T/m, (b) B ¼ 407 mT, qB/qz ¼ 23.4 T/m, (c) B ¼ 530 mT, qB/qz ¼ 30.6 T/m, (d) B ¼ 640 mT, qB/qz ¼ 38.4 T/m.
the particle, respectively. In the route of B-C, the magnetic attraction force on the particles increased and reached the maximal at the O site. The magnetic attraction force slowed the particles and changed the particle velocity in the z-direction. Consequently the increasing difference of velocity between particles and fluid liquid resulted in an increasing drag force. If the magnetic attraction was larger than the maximal drag force, the particles would be captured and accumulated at the center of the air gap. According to Eqs. (1) and (2), the magnetic attraction on a particle is proportional to the strength of the magnetic field and the field gradient that the particle experiences. Hence, the larger the magnetic flux density and the magnetic field gradient, the larger the magnetic force on a particle, the more accumulation was observed in the center of the air gap when the fluid velocity was same. Because the hydrodynamic force is proportional to the fluid velocity, the larger the fluid velocity, the larger the hydrodynamic force over a particle to be overcome to make the particle still, the less accumulation was observed in the center of the air gap.
4. Conclusions
Fig. 8. Effect of magnetic flux density and the magnetic field gradient on accumulation at the fluid velocity of 0.8 mm/s.
The hydrodynamic drag force (Fd) on the particle is given by Stokes’ law: F d ¼ 6pZRðv vp Þ
(2)
where Z is the medium viscosity, R is the magnetic particle’s radius and v and vp are the velocities of the bulk flow and
Due to special shape of poles, the magnetic field produced was stronger at the center of the air gap than any other place along the symmetrical axis. The magnetic field could aggregate the paramagnetic particles at a distance from the pole, making deep capture. Therefore, the apparatus was fit for the deep targeting. The experiment consisted of pumping a certain volume of the paramagnetic particles suspension through a tube positioned in the center of the poles. The effects of the magnetic flux density, magnetic field gradient and fluid velocity on accumulation of paramagnetic particles were investigated in vitro. The results demonstrated the accumulation of paramagnetic
ARTICLE IN PRESS N. Pei et al. / Journal of Magnetism and Magnetic Materials 321 (2009) 2911–2915
2915
Fig. 9. Images of samples at the magnetic flux density of 720 mT and the magnetic field gradient of 48 T/m and at different velocities of (a) 2.6 mm/s, (b) 1.6 mm/s, (c) 1.1 mm/s and (d) 0.8 mm/s.
Acknowledgments The authors gratefully acknowledge the financial support from the National Natural Science Foundation of China (Grant no. 50574056) and the Graduate Foundation of Shanghai University. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] Fig. 10. Effect of fluid velocity on accumulation at the magnetic flux density of 720 mT and the magnetic field gradient of 48 T/m.
particles increased with increment in magnetic flux density and magnetic field gradient and decreased with increment in the fluid velocity.
Robert Langer, Science 293 (2001) 58. E.J. Furlani, E.P. Furlani, J. Magn. Magn. Mater. 312 (2007) 187. M.O. Avile´s, A.D. Ebner, J.A. Ritter, J. Magn. Magn. Mater. 320 (2008) 2640. M.O. Avile´s, A.D. Ebner, J.A. Ritter, J. Magn. Magn. Mater. 320 (2008) 2704. S. Dandamudi, R.B. Campbell, Biomaterials 28 (2007) 4673. X.Q. Yang, Y.H. Chen, R.X. Yuan, G.H. Chen, E. Blanco, J.M. Gao, X.T. Shuai, Polymer 49 (2008) 3477. X.L. Li, K.L. Yao, Z.L. Liu, J. Magn. Magn. Mater. 320 (2008) 1753. C. Alexiou, W. Arnold, R.J. Klein, F.G. Parak, P. Hulin, C. Bergemann, W. Erhardt, S. Wagenpfeil, A.S. Lu¨bbe, Cancer Res. 60 (2000) 6641. C. Alexiou, R.J. Schmid, R. Jurgons, M. Kremer, G. Wanner, C. Bergemann, E. Huenges, T. Nawroth, W. Arnold, F.G. Parak, Eur. Biophys. J. 35 (2006) 446. A.E. David, Y.Z. Huang, V.C. Yang, J. Control. Release 122 (2007) 315. M.W. Wilson, R.K. Kerlan, N.A. Fidelman, A.P. Venook, J.M. Laberge, J. Koda, R.L. Gordon, Radiology 230 (2004) 287. N.J. Darton, B. Hallmark, et al., Nanomedicine 4 (2008) 19. C. Alexiou, R. Schmid, R. Jurgons, C. Bergemann, W. Arnold, F.G. Parak, J. Drug Target 11 (2003) 139. G.P. Hatch, R.E. Stelter, J. Magn. Magn. Mater. 225 (2001) 262. J.W. Zheng, J.M. Wang, T. Tang, G. Li, H.B. Cheng, S.Q. Zou, Chin.-Germ. J. Clin. Oncol. 5 (2006) 336. J.A. Ritter, A.D. Ebner, K.D. Daniel, K.L. Stewart, J. Magn. Magn. Mater. 280 (2004) 184.