IEEE TRANSACTIONS ON MAGNETICS, VOL. 40, NO. 4, JULY 2004
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Synthesis and Performance of Magnetic Composite Comprising Barium Ferrite and Biopolymer Doug-Youn Lee, Young-Il Oh, Dong-Hyun Kim, Kwang-Mahn Kim, Kyoung-Nam Kim, and Yong-Keun Lee
Abstract—The purpose of this study was to prepare the magnetic polymer composite particles with high ferrite content by encapsulating barium ferrite powders with alginate and investigate their physical and biological properties. The magnetic Ca-alginate composite particles were manufactured by adding barium ferrite-alginate slurry dropwise to a CaCl2 solution. The final product was then completely cleaned and dried. Average size (0.1 1 mm in diameter) of magnetic composite particles was dependent on the ratio of barium ferrite to alginate. The degree of swelling of magnetic Ca-alginate particles was increased as pH increased in aqueous media. The magnetic polymer composite particle was found to maintain high coercivity. The saturation magnetization for the magnetic Ca-alginate composites increased with the increase in the barium ferrite/alginate ratio. The self-heating induced by hysteresis loss under an alternating magnetic field was measured as a function of barium ferrite/alginate ratio in distilled water. The agar overlay test indicated a relatively high cell viability for the L929 cell line upon contact with the magnetic composite particles. Index Terms—Alginate, barium ferrite, hysteresis loss, magnetic polymer composite particle.
I. INTRODUCTION
S
TRUCTURED magnetic materials with high saturation magnetization have potential applications in medical diagnostic technologies, magnetic drug delivery, and hyperthermic cancer treatment. Application of magnetic materials for hyperthermia of biological tissue with the goal of tumor therapy has been known in principle for more than four decades [1]. Hyperthermia has proven to be useful in the treatment of malignant tumors. Heat enhances the ability of chemotherapy to destroy malignant tumors. has been well established as a Barium ferrite BaFe O permanent magnetic material because of its fairly large magnetocrystalline anisotropy and relatively large saturation magnetization [2]. Cross-linked synthetic polymers and different polysaccharides like cellulose and alginate were used as a polymeric matrix for synthesizing magnetic composites with interesting results [3], [4].
Manuscript received October 16, 2003. This work was supported by the Korea Research Foundation Grant (KRF-2002-003-E00145). D.-Y. Lee, Y.-I. Oh, D.-H. Kim, K.-N. Kim, and Y.-K. Lee are with Brain Korea 21 Project for Medical Science, Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, Seoul 120-752, Korea (e-mail:
[email protected]; jerry501@ yumc.yonsei.ac.kr;
[email protected];
[email protected];
[email protected]. ac.kr). K.-M. Kim is with Department and Research Institute of Dental Biomaterials and Bioengineering, College of Dentistry, Yonsei University, Seoul 120-752, Korea (e-mail:
[email protected]). Digital Object Identifier 10.1109/TMAG.2004.829177
Alginate gels are heteropolymer carboxylic acids consisting of -D-mannuronic and -L-guluronic units linked by 1,4-glycosidic bonds. It is formed by contacting an alginate solution with a calcium chloride solution. Ca-alginate microspheres are generally prepared by dropping aqueous alginate into a solution of calcium salt [5]. The aims of our work were to prepare the magnetic polymer composite particles with high ferrite content (up to 10 times the amount of ferrite compared to polymer matrix) by encapsulating barium ferrite powders with alginate and investigating their physical and biological properties. II. MATERIALS AND METHODS A. Preparation of Magnetic Alginate Composite Particles We dissolved 0.4 g of sodium alginate (Showa Chemical, Japan) in 20 ml of distilled water, and a different amount (0.4 4 g) of barium ferrite powder (Aldrich, USA) was dispersed in alginate solution using an ultrasonication method. The resulting barium ferrite-alginate slurry was added dropwise to a CaCl solution (0.45 mol/l) to form magnetic Ca-alginate composite beads. They were separated by filtration and washed several times with water and ethanol. The final product was then completely dried at 40 C under vacuum to obtain black powders (0.1 1 mm in diameter) with a high magnetic response when submitted to the effect of a small magnet. B. Morphological and Dimensional Analysis The morphological and dimensional analyses of the magnetic Ca-alginate composite particles were performed by optical microscopy (KH-1000, Hirox, Japan) and scanning electron microscopy (SEM; S-800, Hitachi Co. Japan). C. Determination of Swelling Degree Swelling tests were performed using an optical microscope equipped with a micrometric device. The magnetic composite particles placed in aqueous solution were observed until equilibrium was reached. At least ten particles were considered for each batch, and the mean value was calculated. D. Magnetic Properties The magnetic properties, such as coercivity (Hc) and saturation magnetization (Ms) of the barium ferrite powder and magnetic alginate composite particles (prepared with various ratio of barium ferrite to alginate) were measured under a magnetic field up to 15 kOe at room temperature using a vibrating sample magnetometer (VSM 7300, Lakeshore, USA).
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IEEE TRANSACTIONS ON MAGNETICS, VOL. 40, NO. 4, JULY 2004
Fig. 1. Size images of magnetic composite particles as a function of a BF/A ratio. (a) BF/A = 1. (b) BF/A = 3. (c) BF/A = 5. (d) BF/A = 10.
E. Temperature Change The temperature rise of the magnetic composite particles under an alternating magnetic field was determined by measuring the temperature of water (5 ml) containing 2 g of the magnetic samples under an alternating magnetic field up to 0.08 mT. F. Cytotoxicity A cytotoxicity test was performed with ISO 10 993 Part 5 entitled “Tests for cytotoxicity: in vitro methods.” We used an established L-929 cell (normal cell, fibroblast connective tissue of a 100-day-old male mouse) lines from American Type Culture Collection (Rockville, MD). Approximately 1.5 to 3 million cells suspended in 10-ml MEM were seeded in 90-mm tissue culture dishes and incubated to confluence (1 to 3 days). The medium was replaced with 10 ml of freshly prepared agar/nutrient medium containing MEM, 5% FBS, 2 mmol/L L-glutamine, 0.15% NaHCO , and 1.5% agarose mixture. Ten milliliters of neutral red was added (0.01% in phosphate-buffered saline), and the cells were incubated for 20 min. Excess dye was then removed, and the test specimens were placed on the agar surface. A copper disk was used as positive control and slide glass as negative control. The dishes were incubated for 24 h. Thereafter, the decolorization and lysis indices were examined under a microscope. III. RESULTS AND DISCUSSIONS
Fig. 2. Scanning electron micrographs showing the surface and internal morphologies (cross-section) of magnetic alginate composite particles. (a) Barium ferrite powder, as received (b) cross-section (BF/A = 10), (c) surface (BF/A = 1), and (d) surface (BF/A = 10).
rite and alginate are the solid components of the particle, and the rest is liquid component before the drying process. The solid content increased as the BF/A ratio increased. During the drying process, water is evaporated, and therefore, particles that contain more barium ferrite become larger. The surface and internal morphologies of magnetic composite particles containing large amount of barium ferrite are shown in Fig. 2. The alginate-rich region exists at the surface of the magnetic composite particle, whereas the barium ferrite-rich region is in the center. The surface of the particle is rougher as the BF/A ratio increases, due to barium ferrite particles embedded in the surface alginate component. B. Swelling Behavior of Magnetic Composite Particles The magnetic alginate composite particles showed significant swelling as pH increased (see Fig. 3). Alginate is an acidic polymer. Therefore, it shows a high swelling property in alkaline solution of pH 13. In addition, the swelling degree of the particles depended on the BF/A ratio. More swelling of the composite particle took place when it had more alginate component.
A. Magnetic Ca-Alginate Composite Particles
C. Magnetic Properties
When barium ferrite-alginate slurry was added dropwise into the CaCl solution, instantly, calcium alginate formed in the surface of the sodium alginate stream, and it maintained a round shape. Initially, the center was unreacted sodium alginate, but over a period of time, the calcium ion diffused into the center and formed a complete calcium alginate structure. The average size of magnetic composite particles was dependent on the ratio of barium ferrite to alginate (BF/A). The size increased as the BF/A ratio increased (see Fig. 1). Barium fer-
The hysteresis curves for barium ferrite and magnetic composites are shown in Fig. 4. Fig. 4 and Table I showed the values of saturation magnetization and coercivity as a function of the BF/A ratio. The Ms values for magnetic composite particles were lower than those for barium ferrite (69.0 emu/g). However, by increasing the BF/A ratio, the Ms value was increased from 11.0 to 46.2 emu/g. The reduction in Ms was due to the incorporation of alginate.
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TABLE I MAGNETIC PROPERTIES UNDER MAGNETIC FIELD UP TO 0.08 mT AS A FUNCTION OF A BF/A RATIO
Fig. 3. Degree of swelling of magnetic alginate composite particles in aqueous buffer at pH 1, 7, and 13 at 37 C for 24 h; V . Initial volume of particle V: Final volume of particle after swelling.
TABLE II CYTOTOXICITY OF MAGNETIC COMPOSITE PARTICLES
creased as the BF/A ratio increased. The high concentration of barium ferrite in magnetic composite particles seemed to influence the cytotoxic effect. IV. CONCLUSIONS
Fig. 4. Hysteresis loops under magnetic field up to 15 of a BF/A ratio.
2 10
Oe as a function
The coercivity value for pure barium ferrite material was 4.1 kOe. The coercivity values for magnetic composite particles were close to that of barium ferrite. A barium ferrite bead encapsulated with alginate was found to maintain the high coercivity. The energy of magnetic composite particles in an external field is proportional to the fraction of magnetic material in a composite particle. The heat-generating property (induced by hysteresis loss) of the magnetic composite particle BF/A was close to that of barium ferrite, which induced temperature rise (see Table I). D. Cytotoxicity The result of the agar overlay test was listed in Table II. The magnetic composite particles showed lower cell cytotoxicity compared with barium ferrite. The magnetic composite materials were ranked noncytotoxic or mildly cytotoxic, whereas barium ferrite was ranked cytotoxic. The cytotoxicity was in-
The average size of magnetic composite particles was dependent on the ratio of barium ferrite to alginate (BF/A). The saturation magnetization and the coercivity of the magnetic composite particles were increased as the BF/A ratio increased. The was close to that of barium temperature variation of BF/A ferrite. The magnetic composite particles showed lower cell cytotoxicity compared to barium ferrite. All these special characteristics make the magnetic Ca-alginate composite particles particularly interesting for biomedical applications, especially hyperthermic cancer treatment and magnetic drug delivery. REFERENCES [1] R. Hiergeist, W. Andra, N. Buske, R. Heergt, I. Hilger, U. Richter, and W. Kaiser, “Application of magnetite ferrofluids for hyperthermia,” J. Magn. Magn. Mater., vol. 201, pp. 420–422, 1999. [2] X. Liu, J. Wang, L. M. Gan, S. C. Ng, and J. Ding, “An ultrafine barium ferrite powder of high coercivity from water-in-oil microemulsion,” J. Magn. Magn. Mater., vol. 184, pp. 344–354, 1998. [3] F. Llanes, D. H. Ryan, and R. H. Marchessault, “Magnetic nanostructured composites using alginates of different M/G ratios as polymeric matrix,” Int. J. Biol. Macromol., vol. 27, pp. 35–40, 2000. [4] L. Raymond, J. F. Revol, and R. H. Marchessault, “In situ synthesis of ferrite in ionic and neutral cellulose gels,” Polymer, vol. 36, pp. 5035–5043, 1995. [5] G. Fundueanu, E. Esposito, D. Mihai, A. Carpov, J. Desbrieres, M. Rinaudo, and C. Nastruzzi, “Preparation and characterization of Ca-alginate microspheres by a new emulsification method,” Int. J. Pharm., vol. 170, pp. 11–21, 1998.
