An Efficient Route to Rattle-Type Fe3O4@SiO2 Hollow Mesoporous

Apr 22, 2009 - An Efficient Route to Rattle-Type Fe3O4@SiO2 Hollow Mesoporous Spheres Using Colloidal Carbon Spheres Templates ... E-mail: ZHU.Yufang@...
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Chem. Mater. 2009, 21, 2547–2553

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An Efficient Route to Rattle-Type Fe3O4@SiO2 Hollow Mesoporous Spheres Using Colloidal Carbon Spheres Templates Yufang Zhu,*,† Emanuel Kockrick,‡ Toshiyuki Ikoma,† Nobutaka Hanagata,† and Stefan Kaskel*,‡ ICYS-Sengen, National Institute for Materials Science (NIMS), 1-2-1 Sengen, Tsukuba, Ibaraki, 305-0047, Japan, and Institut fu¨r Anorganische Chemie, Technische UniVersita¨t Dresden, Mommsenstrasse 6, Dresden, 01069, Germany ReceiVed April 6, 2009

Rattle-type Fe3O4@SiO2 hollow mesoporous spheres with large cavities have been successfully prepared by using the colloidal carbon spheres as the templates. The spheres are well monodisperse and nearly uniform in dimension with particle size of ca. 900 nm. The thickness of the mesoporous silica shell is about 100 nm, and only one Fe3O4 particle of ca. 100 nm in diameter is encapsulated in each hollow mesoporous silica sphere. The magnetic measurement indicated that the Fe3O4@SiO2 hollow mesoporous spheres exhibited ferromagnetic behavior with the magnetization saturation of 1.6 emu/g. Using aspirin as a model drug, the Fe3O4@SiO2 hollow mesoporous spheres showed high drug loading capacity and sustained release property. Therefore, this kind of magnetic hollow mesoporous spheres provides a very promising candidate for application in a targeted drug delivery system.

Introdution In the past few years, more and more reports on mesoprous silica based drug delivery systems have been produced,1-7 because amorphous mesoporous silica materials are a kind of satisfactory drug carrier with the nontoxic nature, adjustable pore diameter, and very high specific surface area with abundant Si-OH bonds on the pore surface. The studies showed that the mesoporous silica spheres with hollow core/ mesoporous shell provide much higher drug loading capacity than the conventional mesoporous silica such as MCM-41 and SBA-15, and they also have the sustained release property.4,5 Furthermore, microspheres are widely accepted as useful drug delivery systems because they can be ingested or injected and present a homogeneous morphology.8-10 On the other hand, the superparamagnetic properties of the magnetic nanoparticles (such as Fe3O4, γ-Fe2O3, and FePt) are of great interest for drug delivery.11 They can carry * Corresponding author. E-mail: [email protected] (Y.Z.); [email protected] (S.K.). Fax: 81-29-8592200 (Y.Z.); 49-351-46337287 (S.K.). † National Institute for Materials Science. ‡ Technische Universita¨t Dresden.

(1) Vallet-Regı´, M.; Ra´mila, A.; Del Real, R. P.; Pe´rez-Pariente, J. Chem. Mater. 2001, 13, 308. (2) Lai, C.-Y. V.; Trewyn, B. G.; Jeftinija, D. M.; Jeftinija, K; Xu, S.; Jeftinija, S.; Lin, V. S.-Y. J. Am. Chem. Soc. 2003, 125, 4451. (3) Mal, N. K.; Fujiwara, M.; Tanaka, Y. Nature (London) 2003, 421, 350. (4) Zhu, Y.; Shi, J.; Shen, W.; Chen, H.; Dong, X.; Ruan, M. Nanotechnology 2005, 16, 2633. (5) Zhu, Y.; Shi, J.; Shen, W.; Dong, X.; Feng, J.; Ruan, M.; Li, Y. Angew. Chem., Int. Ed. 2005, 44, 5083. (6) Vallet-Regı´, M.; Balas, F.; Arcos, D. Angew. Chem., Int. Ed. 2007, 46, 2. (7) Trewyn, B. G.; Giri, S.; Slowing, I. I.; Lin, V. S.-Y. Chem. Commun. 2007, 3236. (8) Vasir, J. L.; Tambwekar, K.; Garg, S. Int. J. Pharm. 2003, 255, 13. (9) Kawaguchi, H. Prog. Polym. Sci. 2000, 25, 1171. (10) Freiberg, S.; Zhu, X. X. Int. J. Pharm. 2004, 282, 1.

the drugs and be guided to the targeted organs or locations inside the body, which will facilitate the therapeuthic efficiency and avoid the damage of normal organs or tissues due to the drug toxicity before targeting the desired positions. In general, magnetic nanoparticles are necessary to be protected by diverse species (silica, surfactant polymers, and nonpolymeric organic stabilizers),12-14 which is aimed at avoiding contact between the magnetic nanoparticles and the tissue while maintaining the colloidal suspension stability within the biological environment. Therefore, the magnetic nanoparticles together with mesoporous silica represent a significant advance in the field of drug delivery. Recently, several strategies have been developed to obtain this kind of magnetic mesoporous silica nanocomposites. One is based on core/shell structures.15-18 For example, Shi’s group reported the uniform magnetic nanocomposite spheres with a magnetic core/mesoporous silica shell structure as drug delivery carriers.15 Vallet-Regı´’s group demonstrated the synthesis of spherical silica-based mesoporous materials encapsulating magnetic γ-Fe2O3 nanoparticles by using an aerosol-assisted route, and higher amount of γ-Fe2O3 nanoparticles can be embedded in mesoporous silica.16 However, (11) Lu¨bbe, A.; Bergemann, C.; Brock, J.; McClure, D. G. J. Magn. Magn. Mater. 1999, 194, 149. (12) Philipse, A. P.; Van Bruggen, M. P. B.; Pathmamanoharan, C. Langmuir 1994, 10, 92. (13) Jain, T. K.; Morales, M. A.; Sahoo, S. K.; Leslie-Pelecky, D. L.; Labhasetwar, V. Mol. Pharmacol. 2005, 2, 194. (14) Portet, D.; Denizot, B.; Rump, E.; Lejeune, J. J.; Jallet, P. J. Colloid Interface Sci. 2001, 238, 37. (15) Zhao, W.; Gu, J.; Zhang, L.; Chen, H.; Shi, J. J. Am. Chem. Soc. 2005, 127, 8916. (16) Ruiz-Herna´ndez, E.; Lo´pez-Noriega, A.; Arcos, D.; Izquierdo-Barba, I.; Terasaki, O.; Vallet-Regı´, M. Chem. Mater. 2007, 19, 3455. (17) Kim, J.; Lee, J.; Lee, J.; Yu, J.; Kim, B.; An, K.; Hwang, Y.; Shin, C.; Park, J.; Kim, J.; Hyeon, T. J. Am. Chem. Soc. 2006, 128, 688. (18) Liong, M.; Lu, J.; Kovochich, M.; Xia, T.; Ruehm, S. G.; Nel, A. E.; Tamanoi, F.; Zink, J. I. ACS Nano 2008, 2, 889.

10.1021/cm900956j CCC: $40.75  2009 American Chemical Society Published on Web 04/22/2009

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these magnetic nanocomposites showed relatively low drug loading. The other is the encapsulation of magnetic nanoparticles in the channels of mesoporous silica.19,20 In this case, magnetic nanoparticles often block the mesoporous channels, which results in the lower drug loading and poor release property. Obviously, to combine the magnetic nanoparticles and hollow mesoporous silica spheres to form rattle-type magnetic core/mesoporous shell silica spheres will realize high drug loading and the magnetic targeting delivery. To date, rattle-type spheres as an important extension of core/shell particles have mostly been synthesized via the template method involving the preparations of middle layer and outer shell on preformed inner core and subsequent removal of the middle layer.21-24 However, different materials should be selected for the inner core, the middle layer, and the outer shell to guarantee that the inner core and outer shell still exist during the procedure for the removal of the middle layer. Another strategy is to form the inner core within the preformed shell,25 i.e., the precursor of the inner core first permeates into the preformed hollow sphere; subsequently, the precursor is transformed into the desired inner core. Very recently, Zhao et al. reported rattle-type hollow magnetic mesoporous spheres by using hydrothermal treatment of Fe2O3/SiO2/MSiO2 core/shell structure, and then reduced them in a H2/N2 atmosphere. However, the cavity between magnetic core and mesoporous shell is very limited, and the synthetic procedure is rather complex.26 Zhang et al. demonstrated the preparation of hollow mesoporous organosilica with Fe3O4 nanocrystals in the hollow cores by using oil-in-water microemulsion strategy.27 Xuan et al. reported the fabrication of magnetic hollow silica particles with nonporous silica shell using β-FeOOH/SiO2 core/shell-like particles as the template.28 Zhou et al. developed porous magnetic hollow silica spheres through Fe3O4/CaCO3 composite nanoaprticles as the templates, but the particles are seriously aggregated because of the poor dispersion of the Fe3O4/CaCO3 templates.29 Recently, an interesting sacrificial template, monodisperse carbon sphere, has been easily prepared by the hydrothermal treatment of aqueous solutions of glucose and polysaccharides.30 These carbon spheres inherit functional groups such as -OH and -CdO on the surface, which offer an important chemical environment for the adsorption of metal precursors and nanoparticles. Therefore, a variety of hollow spheres (19) Cannas, C.; Musu, E.; Musinu, A.; Piccaluga, G.; Spano, G. J. NonCryst. Solids 2004, 345 & 346, 653. (20) Yiu, H. H. P.; Keane, M. A.; Lethbridge, Z. A. D.; Lees, M. R.; El Haj, A. J.; Dobson, J. Nanotechnology 2008, 19, 255606. (21) Kim, J. Y.; Yoon, S. B.; Yu, J.-S. Chem. Commun. 2003, 790. (22) Kim, M.; Sohn, K.; Na, H. B.; Hyeon, T. Nano Lett. 2002, 2, 1383. (23) Lou, X. W.; Yuan, C.; Archer, L. A. Small 2007, 3, 261. (24) Choi, W. S.; Koo, H. Y.; Kim, D.-Y. AdV. Mater. 2007, 19, 451. (25) Hah, H. J.; Um, J. I.; Han, S. H.; Koo, S. M. Chem. Commun. 2004, 1012. (26) Zhao, W.; Chen, H.; Li, Y.; Li, L.; Lang, M.; Shi, J. AdV. Funct. Mater. 2008, 18, 2780. (27) Zhang, L.; Qiao, S.; Jin, Y.; Chen, Z.; Gu, H.; Lu, G. Q. AdV. Mater. 2008, 20, 805. (28) Xuan, S.; Liang, F.; Shu, K. J. Magn. Magn. Mater. 2009, 321, 1029. (29) Zhou, J.; Wu, W.; Caruntu, D.; Yu, M. H.; Martin, A.; Chen, J. F.; O’Connor, C. J.; Zhou, W. L. J. Phys. Chem. C 2007, 111, 17473. (30) Sun, X.; Li, Y. Angew. Chem., Int. Ed. 2004, 43, 597.

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Figure 1. Schematic procedure for the preparation of rattle-type Fe3O4@SiO2 hollow mesoporous spheres.

have been prepared by templating colloidal carbon spheres, such as SiO2, TiO2, WO3, Fe2O3, Pt, SnO2, Ga2O3, and so on.31-36 However, to the best of our knowledge, no report on the preparation of rattle-type magnetic hollow mesoporous silica spheres based on colloidal carbon spheres templates can be found. In this paper, we reported an efficient route to prepare rattle-type Fe3O4@SiO2 hollow mesoporous spheres with large cavities by using the colloidal carbon spheres as the templates. The schematic procedure for the preparation of rattle-type Fe3O4@SiO2 hollow mesoporous spheres is shown in Figure 1. The first step involved the preparation of the colloidal carbon spheres adsorbed with iron precursor by a one-pot hydrothermal treatment. In the next step, the organosilicate-incorporated silica shells were deposited on the colloidal carbon spheres through the simultaneous sol-gel polymerization of tetraethoxysilane (TEOS) and n-octadecyltrimethoxysilane (C18TMS). Finally, the rattle-type Fe3O4@SiO2 hollow mesoporous spheres were obtained after the calcination to remove the carbon templates and the organic groups of C18TMS, and then the reduction under hydrogen atmosphere. Furthermore, by use of the colloidal carbon spheres without iron precursor as the templates, mesoporous hollow silica spheres can also be prepared through this strategy. Experimental Section Preparation of Iron Precursor. One milliliter of Fe3Cl3 · 6H2O (3 mol/L), 3 mL of HCl (0.2 mol/L), and 296 mL of H2O were added in a flask. The solution was refluxed for 2 h, followed by evaporating for several hours to get ca. 50 mL of red solution using rotary evaporator. Preparation of Colloidal Carbon Spheres Adsorbed with Iron Precursors. Three grams of glucose and 3 mL of iron precursor were dissolved in 28 mL of H2O to form a red transparent solution, which was added to a 50 mL Teflon-sealed autoclave and maintained at 170 °C for 10 h. The puce products were isolated by centrifugation, cleaned by four cycles of centrifugation/washing/ redispersion in ethanol, and dried at room temperature for 2 days. (31) Titirici, M.-M.; Antonietti, M.; Thomas, A. Chem. Mater. 2006, 18, 3808. (32) Zheng, M.; Cao, J.; Chang, X.; Wang, J.; Liu, J.; Ma, X. Mater. Lett. 2006, 60, 2991. (33) Wang, C.; Chu, X.; Wu, M. Sens. Actuators, B 2007, 120, 508. (34) Li, X.; Lou, T.; Sun, X.; Li, Y. Inorg. Chem. 2004, 43, 5442. (35) Sun, X.; Li, Y. Angew. Chem., Int. Ed. 2004, 43, 3827. (36) Yang, R.; Li, H.; Qiu, X.; Chen, L. Chem.sEur. J. 2006, 12, 4083.

Rattle-Type Fe3O4@SiO2 Hollow Spheres Preparation of Rattle-Type Fe3O4@SiO2 Hollow Mesoporous Spheres. First, 0.2 g of the colloidal carbon spheres adsorbed with iron precursors was added to 100 mL of a poly(vinylpyrrolidone) (PVP, K30, 1.0 g) ethanol solution. After stirring for 12 h, the carbon spheres were separated by centrifugation. Subsequently, the obtained carbon spheres templates were dispersed in a solution composed of 75 mL of ethanol (EtOH), 10 mL of H2O, and 3.8 mL of NH3 · H2O (25 wt %). After being stirred for 30 min, 0.4 mL of the mixture with a 4.7:1 TEOS: C18TMS molar ratio was added dropwise using a 1 mL syringe to the reaction mixture under vigorous stirring and subsequently stirred at room temperature for 8 h. The resultant particles were separated by centrifugation, cleaned by three cycles of centrifugation/washing/redispersion in ethanol, and dried at room temperature for 12 h. Finally, the as-prepared products were calcined in air at 550 °C for 6 h, and then reduced in 5% H2/ 95% Ar at 350 °C for 2 h. The sample was named as Fe3O4@SiO2. Drug Storage. Aspirin (Sigma, 99%) was dissolved in anhydrous ethanol (dried over 4Å molecular sieves prior to use). One gram of the Fe3O4@SiO2 hollow mesoporous spheres was added to 25 mL of aspirin anhydrous ethanol solution with a concentration of 40 mg/mL at room temperature. The vials were sealed to prevent the evaporation of ethanol, and the mixture was then stirred for 24 h. The product was filtered and dried under a vacuum at 60 °C. The sample was named as Fe3O4@SiO2aspirin. The filtrate was extracted from the vial and analyzed by UV/vis spectroscopy at a wavelength of 276 nm. In vitro Drug Release. One-tenth of a gram of the sample of the Fe3O4@SiO2-aspirin was immersed into 100 mL of phosphate buffer silane (PBS, pH 7.4, 5.0 and 2.5) at 37 °C under stirring at 100 rpm. The release medium (1.0 mL) of the sample was removed for analysis at given time intervals using a syringe and replaced with the same volume of fresh preheated PBS. The extracted medium was analyzed by UV/vis spectroscopy at a wavelength of 298 nm.37 This wavelength is a little different from 276 nm, because aspirin has been hydrolyzed to salicylic acid during release from the mesoporous carrier in PBS. Calculation of the corrected concentration of the released aspirin is based on the equation38

Ctcorr ) Ct +

V V

t-1

∑ Ct 0

Where Ctcorr is the corrected concentration at time t, Ct is the apparent concentration at time t, V is the volume of sample taken, and V is the total volume of dissolution medium. Characterization Methods. The wide-angle X-ray diffraction (WAXRD) pattern was obtained on a Stoe Stadi P powder diffractometer equipped with a curved germanium (111) monochromator and linear PSD using Cu KR1 radiation (1.5405 Å) in transmission geometry. Scanning electron microscopy (SEM) was carried out on Zeiss DMS 982 Gemini field emission scanning electron microscopy and JSM-6700F field emission scanning electron microscope. Transmission electron microscopy (TEM) was performed using a JEOL 2100F and JEOL 2100 electron microscope operated at 200 kV acceleration voltages. Fourier-transform infrared (FTIR) spectra were recorded on a Nicolet 7000-C spectrometer prepared by mixing the materials with KBr. The UV/vis absorption spectra were measured using a Shimadzu UV-1650PC spectropho(37) Andreopoulos, A. G.; Hatzi, E.; Doxastakis, M. J. Mater. Sci.: Mater. Med. 2001, 12, 233. (38) Fisher, K. A.; Huddersman, K. D.; Taylor, M. J. Eur. J. Chem. 2003, 9, 5873.

Chem. Mater., Vol. 21, No. 12, 2009 2549 tometer. N2 adsorption-desorption isotherms were obtained on a Quantachrome Autosorb 1C apparatus at -196 °C under continuous adsorption condition. Thermogravimetric analysis (TG) measurement was performed using Netzsch STA-409C thermogravity analyzer at a scanning rate of 2 °C/min under N2 atmosphere. Magnetic measurement was carried out on a SQUID magnetometer at room temperature. Fe content was analyzed by ICP-OES (PE-3300DV) after the sample was dissolved by HF and HNO3.

Results and Discussion Images a and b in Figure 2 show the SEM and TEM images of the initial colloidal carbon spheres templates produced via the hydrothermal treatment of glucose/water solution with iron precursors. It can be seen that the colloidal carbon spheres are monodisperse and uniform with diameters of ca. 1 µm. After the calcination of these colloidal carbon spheres templates at 550 °C under air atmosphere, red powders were collected. The SEM observation shows that the red powders are the small hollow nanoparticles with the diameter of ca. 100 nm (Figure 2c). The XRD pattern indicated that these red particles are R-Fe2O3 according to the reflection peak positions and relative intensities (Figure 2d). This confirmed that the iron precursors were adsorbed on the colloidal carbon spheres. As previous reported,30 the mechanism of the formation of the carbon spheres via the hydrothermal treatment of glucose/water solution involves the dehydration of the carbohydrate in the first step and subsequent carbonization of the so-formed organic compounds in the second step. The surface of the spheres is hydrophilic and has a distribution of OH and CdO groups, and thus iron ions and colloidal nanocrystals can be adsorbed near the shell of the carbon spheres during the hydrothermal treatment process. Several reports have demonstrated the synthesis of hollow metal oxides using a similar strategy.31-36 Therefore, it provides the possibility to obtain the monodisperse Fe3O4@SiO2 hollow mesoporous spheres with a narrow particle size distribution. Figure 3 shows the SEM and TEM images of the Fe3O4@SiO2 hollow mesoporous spheres. As expected, these spheres are well monodisperse and nearly uniform in dimension with particle diameters of ca. 900 nm. The silica shell is about 100 nm in thickness. From the high-magnification TEM image in Figure 3d, disordered mesopores are distributed on the shells. It is interesting that only one small particle of ca. 100 nm in diameter is encapsulated in each hollow mesoporous silica sphere. The energy-dispersive X-ray (EDX) spectrum on the small particles showed the existence of Fe element, but no Fe element can be detected in other areas of the spheres. The wideangle XRD pattern showed the (311) and (440) diffraction peaks of Fe3O4 phase in this sample (Figure 4a). Therefore, it can be presumed that the small particle is magnetic Fe3O4. Here, only two weak diffraction peaks are presented on the XRD pattern, which is due to the low Fe content in the sample (0.67 wt % Fe in the sample measured by ICP-OES) and the overlap of the diffraction peaks of Fe3O4 and amorphous SiO2. Although the diffraction peaks of γ-Fe2O3 and Fe3O4 are quite similar, the black color of the sample and the presence of reductive atmosphere during the preparation process indicate the presence of Fe3O4 rather than γ-Fe2O3 (red color).

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Figure 2. (a) SEM and (b) TEM images of the carbon templeates; (c) SEM image and (d) XRD pattern of the sample of the carbon templates after being calcined at 550 °C.

Figure 3. SEM and TEM images of the Fe3O4@SiO2 hollow mesoporous spheres.

To further confirm the crystalline structure and the size of magnetic Fe3O4 small particles in the hollow mesoporous silica spheres, we used the XRD measurement and TEM observation to analyze the sample of the Fe3O4@SiO2 after the dissolution of the outer silica shells (the silica shells were removed by twice dissolution with heated 2 M NaOH solution). The XRD pattern of the sample of the Fe3O4@SiO2 after the dissolution of the outer silica shells is shown in

Figure 4a. It can be found that well-resolved diffraction peaks appeared on the pattern, and the pattern can be easily indexed to Fe3O4 (JCPDS 75-1609) according to the reflection peak positions and relative intensities, which confirms the magnetite structure of this sample. Figure 4b shows the TEM image of the sample of the Fe3O4@SiO2 after the dissolution of the outer silica shells. It can be seen that the Fe3O4 particle is spherical and the size is about 100 nm in diameter, which

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Figure 5. Nitrogen adsorption-desorption isotherm of the Fe3O4@SiO2 hollow mesoporous spheres before and after aspirin loading (the inset is the pore size distribution).

Figure 4. (a) XRD patterns of the Fe3O4@SiO2 hollow mesoporous spheres before and after the dissolution of the silica shells; (b) TEM image of the sample of the Fe3O4@SiO2 hollow mesoporous spheres after the dissolution of the silica shells (the inset is the SAED image).

is consistent with the result before the dissolution of the outer silica shells. It can also be observed that the Fe3O4 nanoparticles are hollow and small particles with ca. 10 nm are aggregated to form the shell. The selected area electron diffraction (SAED, the inset of Figure 4b) gives the characteristic diffraction rings of the Fe3O4 polycrystal. The nitrogen adsorption-desorption isotherm of the Fe3O4@SiO2 hollow mesoporous spheres and its corresponding pore size distribution curve are shown in Figure 5. The isotherm can be classified as type IV isotherms characteristic of mesoporous materials. The corresponding pore size distribution data calculated from the desorption branch of the nitrogen isotherm by the BJH (Barrett-Joyner-Halenda) method shows a narrow pore size distribution peaked at 2.5 nm. The specific surface area can reach 860 m2/g calculated from the linear part of the BET (Brunauer-Emmett-Teller) plot. The single point adsorption total volume at P/P0 ) 0.90 is 0.647 cm3/g. According to the above results and the previous reports,15,26,32 the formation of the mesoporous silica shell surrounding the colloidal carbon spheres can be described as follows. When the silica sources (TEOS and C18TMS) were added into the EtOH/H2O solution with the colloidal carbon spheres, TEOS and C18TMS would hydrolyze, respectively. The hydrolyzed TEOS will form the silica oligomers, and the hydrolyzed

C18TMS will form the micelles via the hydrophobic carbon chains of C18TMS. On the other hand, the co-condensation would subsequently begin because of the presence of NH3 · H2O. The organic-inorganic primary particles in a disordered fashion will be formed via very strong covalent bonding between the ethoxy groups of TEOS and the methoxy groups of C18TMS. Finally, the organic-inorganic primary particles deposited on the surfaces of the colloidal carbon spheres. Here, PVP was used to modify the colloidal carbon templates, which is due to the amphiphilic characteristic of PVP and will facilitate the deposition of the primary particles on the templates. When the colloidal carbon templates without PVP modification were used in the reaction, many pure mesoporous silica particles were formed besides the Fe3O4@SiO2 hollow mesoporous spheres. Figure 6a shows the magnetization curve measured at room temperature for the Fe3O4@SiO2 hollow mesoporous spheres. The curve presents a small hysteresis loop, which suggests that the Fe3O4@SiO2 hollow mesoporous spheres have ferromagnetic behavior. It has been reported that the magnetic Fe3O4 particles exhibit superparamagnetic behavior when the particle size decreases to below a critical value, generally around 20 nm.39 Although the primary Fe3O4 particles are only ca. 10 nm, they are aggregated and connected to form the big hollow particles with the diameter of ca. 100 nm, which results into the ferromagnetic behavior. The Ms (magnetization saturation) value is about 1.6 emu/g. The magnetic separation ability of the sample was tested in PBS solution by placing a magnet near the glass bottle. The black particles were attracted toward the magnet within a short period (Figure 6b). Therefore, this will provide an easy and efficient way to separate the Fe3O4@SiO2 hollow mesoporous spheres from a suspension system and to carry drugs to targeted locations under an external magnetic field. To evaluate the capability of the Fe3O4@SiO2 hollow mesoporous spheres for drug delivery system, aspirin, a typical anti-inflammatory drug, was introduced into the Fe3O4@SiO2 hollow mesoporous spheres. The amount of nitrogen adsorption of the sample decreased sharply after loading aspirin (Figure 5), which is attributed to the inclusion of aspirin molecules in the pore channels. Figure 7 shows the FTIR spectra of aspirin and the Fe3O4@SiO2 hollow (39) He, Y. P.; Wang, S. Q.; Li, C. R.; Miao, Y. M.; Wu, Z. Y.; Zou, B. S. J. Phys. D: Appl.Phys. 2005, 38, 1342.

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Figure 6. (a) Magnetization curve measured at 300 K for the Fe3O4@SiO2 hollow mesoporous spheres; (b) magnetic separation from PBS solution under an external magnet.

Figure 7. FTIR spectra of aspirin and the Fe3O4@SiO2 hollow mesoporous spheres before and after loading aspirin.

Figure 8. TG curves of the Fe3O4@SiO2 hollow mesoporous spheres and MCM-41 after loading aspirin.

mesoporous spheres before and after loading aspirin. After loading aspirin, the sample of the Fe3O4@SiO2-aspirin shows a weak band at 1700 cm-1, which correspondsto the carboxylic group of aspirin. This indicated that part of the aspirin molecules interact with pore walls through hydrogen bonding. Two bands at 1470 and 1380 cm-1 correspond to the C-H bending vibration in the aspirin molecules. The band at 1760 cm-1 corresponding to COO- groups of aspirin is still present on the spectrum, which also suggests that aspirin does not degrade. Therefore, it further proves that aspirin has been loaded in the Fe3O4@SiO2 hollow mesoporous spheres. The uptake amount of aspirin in the Fe3O4@SiO2 hollow mesoporous spheres can be assessed by TG analysis (Figure 8). It can be found that the weight loss is about 27.7 wt %, except the weight loss of physical water, which suggested that the uptake amount of aspirin in the Fe3O4@SiO2 hollow

Figure 9. Aspirin release behavior from the Fe3O4@SiO2 hollow mesoporous spheres in different pH solutions.

mesoporous spheres is 27.7 wt %. Compared to the conventional MCM-41 with an uptake amount of 16.5 wt % (surface area of 1152m2/g and pore volume of 0.99 cm3/g for MCM41), the Fe3O4@SiO2 hollow mesoporous spheres showed much higher drug loading capacity. It can be believed that the hollow structure plays an important role on the high drug loading capacity. Figure 9 shows the release behavior of aspirin from the Fe3O4@SiO2-aspirin system in PBS with different pH values over a 60 h period. The release was relatively fast within 12 h, and then the drug was released in a more controlled fashion until the end of the assay. Obviously, the Fe3O4@SiO2aspirin system has sustained release property, and this kind of kinetics is useful for those clinical cases that require a first high dose followed by a more stable dosage. Furthermore, the aspirin release rate increases with the increase in pH values. Generally, the release of drug stored in mesoporous silica carrier occurs only after the solution penetrated into the channels and the drug being dissolved, then followed by diffusion along aqueous pathways into the solution. On the other hand, the solubility of aspirin increases with the increase in the pH values in the solution. Therefore, the confined effect of the mesopore channels and the solubility of aspirin in different pH solutions determined the sustained release and the different release rate in different pH solutions. To determine if the release behavior of aspirin molecules from the Fe3O4@SiO2-aspirin system is governed by Fickian diffusion, we fitted these results to the Higuchi model.40,41 According to the model, a straight line for the plot suggests (40) Peppas, N. A. Pharm. Acta HelV. 1985, 60, 110.

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that drug release follows a Fickian diffusion mechanism. The linear profiles of the release amount versus root time in the inset of Figure 9 suggest that aspirin release from the Fe3O4@SiO2-aspirin system is consistent with a Fickian diffusion mechanism. Because only part of aspirin molecules interact with pore wall through the hydrogen bonding, which is so weak that aspirin molecules can be relatively easy to be cleaved from the carriers. Besides, most of aspirin molecules loaded in Fe3O4@SiO2 are physical state. Therefore, the counter outward diffusion of aspirin from the pore channels on the shells is the controlling process in the drug release. Conclusion In this paper, an efficient colloidal carbon sphere templating route has been developed to prepare rattle-type Fe3O4@SiO2 hollow mesoporous spheres. The inner Fe3O4 movable core endues the spheres with magnetic property. The outer mesoporous silica shell provides the pathway for (41) Bajpal, A. K.; Bajpal, J.; Shukla, S. J. Mater. Sci.: Mater. Med. 2003, 14, 347.

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guest molecules to diffuse into or out from the hollow core. The aspirin uptake capacity can reach 27.7 wt %, much higher than the conventional MCM-41. The in vitro release test showed that the Fe3O4@SiO2-aspirin system has sustained release property governed by Fickian diffusion, and the release rate increased with the increase of the pH values. Therefore, this kind of magnetic hollow mesoporous spheres provides a very promising candidate applicable in targeted drug delivery system. Acknowledgment. The work was supported by International Center for Young Scientists (ICYS), National Institute for Materials Science (NIMS), Key Laboratory of Inorganic and Composite New Materials of Jiangsu Province (Wjjqfhxcl200804), and Alexander von Humboldt Foundation. Y.Z. also thanks Dr. Shinji Itoh for measuring the Fe content by ICP-OES. Supporting Information Available: SEM and TEM images of hollow mesoporous silica spheres and the Fe3O4@SiO2 hollow mesoporous spheres obtained by using the carbon spheres without PVP modification, EDX spectrum the Fe3O4@SiO2 hollow mesoporous spheres (PDF). This material is available free of charge via the Internet at http://pubs.acs.org. CM900956J