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J. Phys. Chem. C 2008, 112, 7130-7137
Synthesis and Characterization of Magnetic FexOy@SBA-15 Composites with Different Morphologies for Controlled Drug Release and Targeting Shanshan Huang, Piaoping Yang, Ziyong Cheng, Chunxia Li, Yong Fan, Deyan Kong, and Jun Lin* State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China ReceiVed: January 15, 2008; In Final Form: February 29, 2008
Magnetic functionalization of the ordered mesoporous SBA-15 (SiO2) aggregate blocks and rice grain-like particles were realized by using a sol-gel method, resulting in the formation of FexOy@SBA-15 composite materials. The X-ray diffraction (XRD), N2 adsorption/desorption, and transmission electron microscopy (TEM) results show that these composites conserved ordered mesoporous structure after the formation of FexOy nanoparticles in the pores and on the outer surface of SBA-15. It was confirmed by the XRD and X-ray photoelectron spectroscopy (XPS) analysis that the FexOy generated in these mesoporous silica hosts is mainly composed of γ-Fe2O3. Magnetic measurements reveal that these composites possess superparamagnetic properties at 300 K. The saturation magnetization of these composites increased with the increasing loading amount of γ-Fe2O3. These composites, which possess high surface area and high pore volume, show magnetic response sufficient for drug targeting in the presence of an external magnetic field. These magnetic composites show sustained release profiles with ibuprofen as the model drug. The rice grain-like Fe xOy@SBA-15 particles show higher release rate with respect to the FexOy@SBA-15 aggregate blocks.
1. Introduction Recently, various magnetic composite materials have been extensively studied due to their broad application from industrial to biomedical fields, such as contrast agents in magnetic resonance imaging (MRI), as carriers for targeting drug delivery, in biomagnetic separations, and in biosensors.1 For magnetic drug targeting, the drug immobilized on a microparticulate carrier possessing magnetic properties has gained much interest.2 Magnetic drug targeting allows the release of drugs at a defined target site with the aid of a magnetic field. These are desirable characteristics for drug targeting/delivery applications: a sufficient magnetization in the presence of a magnetic field is desired to direct the vectors to the target region; however, once the magnetic field is eliminated, it is also required that the particles show a low tendency to form agglomerates, and this is aided by both a low remanence and a low coercivity.3 So far, different types of magnetic micro- and nanoparticles have been developed. Particularly, applications of porous magnetic materials have gained great attention.4 Researches for preparation of porous magnetic materials have been centered on two approaches: (i) creation of magnetic particles in asprepared porous matrix; (ii) synthesis of porous layer on the surface of magnetic nanoparticles. Magnetically functionalization of mesoporous materials such as SBA-15, MCM-41, and MCM-48 by the first approach has been studied by many researchers.5 These ordered mesoporous silica have gained considerable attention for following reasons: (i) These materials possess a network of channels and voids of well-defined size in nanoscale range (2-50 nm). This particular pore architecture makes them suitable candidates for hosting a variety of molecules. (ii) The main silica component can easily be functionalized because of their high specific surface area with * Corresponding author. E-mail:
[email protected].
abundant Si-OH active bonds on the pore walls. (iii) The silica base is nontoxic and highly biocompatible for applications in drug delivery system.6 Drug targeting need materials exhibit magnetic response sufficient for magnetic separation from the solution combined with high adsorption capacity. Previous studies are mainly focused on magnetic functionalization of classical SBA-15 with aggregation of rodlike morphology. Nanoparticles of paramagnetic R-Fe2O3 in the pores of SBA15 were synthesized by thermolysis of Fe(NO3)3 inside the pores,7 but the magnetization of the sample was low for drug targeting. Delahaye et al. obtained ultrasmall γ-Fe2O3 by using the “two solvents” wetness impregnation technique;8 however, they did not mention the potential for drug targeting of these magnetic FeOx-loaded SBA-15 samples. Meanwhile, particle size and morphology are important in drug targeting because the ability of the particles to reach a given location in the body is limited by the size of the vessels of the human circulatory system, with radii of 0.08-7.5, 0.005-0.07, and 0.004 mm for arteries, arterioles, and capillaries, respectively.9 Thus, it is necessary to design magnetic composites with different particle size for different targeted organs. The aim of our work is to synthesize magnetically functionalized SBA-15 with different morphologies and study its potential application as carriers in drug targeting system. We obtained magnetically functionalized classical SBA-15 aggregate blocks and rice grain-like SBA-15 particles by generating magnetic FexOy in the pores and on the outer surface of the mesoporous silica using the sol-gel method. The properties of these composites were well characterized by XRD, XPS, FTIR, SEM, TEM, N2 adsorption/desorption, and magnetic measurement. Ibuprofen (IBU) was chosen as the model drug to study the storage capacity and delivery profiles of these composites for the application of drug targeting.
10.1021/jp800363s CCC: $40.75 © 2008 American Chemical Society Published on Web 04/15/2008
Magnetic FexOy@SBA-15 Composites 2. Experimental Section 2.1. Materials and Synthesis. 2.1.1. Synthesis of SBA-15. The materials for the synthesis of SBA-15 included tetraethyl orthosilicate (TEOS, 99%, Beijing Chemical Reagent Co., Beijing), hydrochloric acid (36-38%, Beijing Chemical Reagent Co., Beijing), and (EO)20(PO)70(EO)20 (P123, Mw ) 5800, Aldrich). All chemicals are of analytical reagents (A.R.) and used directly without further purification. Classical SBA-15 silica blocks were synthesized as reported by Zhao et al. using triblock copolymer P123 as template.10 Rice grain-like SBA15 silica particles were synthesized according to the published process.11 Typically, 4.0 g of P123 was dissolved in 30 g of H2O and 120 g of diluted HCl solution (pH ) 2.0) with stirring at 35 °C. Then 8.5 g of TEOS was added dropwise to the solution with vigorous stirring. After 5 min of stirring, the mixture was kept under static conditions at 35 °C for 20 h and then heated at 90 °C for 24 h. The obtained samples were filtered, washed, and dried in air at room temperature. The assynthesized materials were calcined from room temperature to 500 °C at a heating rate of 1 min-1 and kept at 500 °C for 6 h to remove the organic template. 2.1.2. Preparation of FexOy@SBA-15 Composites by SolGel Method.12 A typical process is as follows: 0.3153 g of Fe(acac)3 (iron(III) acetylacetonate, 99.9%, Aldrich) was immersed in mixture of 3.0 mL of CH3COOH (A.R.) and 0.5 mL of HNO3 (A.R.) and then stirred for 4 h to make sure that Fe(acac)3 was completely dissolved to form a sol. Then 0.25 g of SBA-15 powder (aggregate blocks) was added into the above sol solution. After stirring under room temperature for another 4 h, the mixture was then left stand overnight to let the acid evaporate. Then the sample was collected and heated from room temperature to 500 °C with a heating rate of 2 °C min-1 and maintained at 500 °C for 2 h in air, resulting in the formation of FexOy@SBA-15 composites. For the rice grain-like SBA-15 silica particles, calcination temperatures from 300 to 500 °C were investigated, and a magnetic composite was obtained at lower calcination temperature of 350 °C for 30 min. 2.1.3. Drug Adsorption and in Vitro Release. Typically, 0.2 g of FexOy@SBA-15 sample was suspended in a 20 mL hexane solution of ibuprofen (with a concentration of 35 mg mL-1) at room temperature under stirring for 48 h in a sealed vial to prevent the evaporation of the hexane. After loading of the drug, the samples were collected by centrifugation, washed gently by the hexane, and then dried at 60 °C under vacuum for 10 h. The amounts of IBU loaded were determined by thermogravimetry (TG) analysis. After drug loading, the obtained samples were compressed into tablets of 10 × 0.5 mm2, and the delivery rates were obtained by soaking the 100 mg drug-charged tablets into 50 mL of simulated body fluid (SBF, pH ) 7.4)13 maintained at 37 °C. At predetermined time intervals, 1 mL of the sample was withdrawn and immediately replaced with an equal volume of dissolution medium to keep the volume constant. The withdrawn samples were filtered, properly diluted, and monitored by a UV-vis spectrophotometer at 272 nm. 2.2. Characterization. X-ray power diffraction (XRD) was performed on a Rigaku-Dmax 2500 diffractometer using Cu KR radiation (λ ) 0.154 05 nm). Fourier-transform IR spectra were recorded on a Perkin-Elmer 580B IR spectrophotometer using the KBr pellet technique. N2 adsorption/desorption isotherms were obtained on a Micromeritics 2020M apparatus. Pore size distribution was calculated from the adsorption branch of N2 adsorption/desorption isotherm and the Barret-Joner-Halenda (BJH) method. The Brunauer-Emmett-Teller (BET) surface
J. Phys. Chem. C, Vol. 112, No. 18, 2008 7131 areas were determined using the data between 0.05 and 0.35 just before the capillary condensation, and the pore volume was obtained by the t-plot method. The morphology and composition of the samples were inspected using a field emission scanning electron microscope (FESEM, XL30, Philips) equipped with an energy-dispersive X-ray spectrum (EDS, JEOL JXA-840). Transmission electron microscopy (TEM) images were obtained from a FEI Tecnai G2 S-Twin transmission electron microscope with a field emission gun operating at 200 kV. Inductively coupled plasma (ICP) measurement (Thermo iCAP 6000 ICPOES) was performed on the sample to determine the exact loading level of FexOy. Magnetization measurements were performed on an MPM5-XL-5 SQUID (superconducting quantum interference device) magnetometer. Thermogravimetry (TG) and differential thermal analysis (DTA) were carried out on a Netzsch STA 409 thermoanalyzer with a heating rate of 5 °C min-1 in a N2 atmosphere. The UV-vis absorption spectra values were measured on a TU-1901 spectrophotometer. 3. Results and Discussion 3.1. XRD and XPS Analysis. Parts a-c of Figure 1A show the low-angle XRD patterns of calcined classical SBA-15, FexOy@SBA-15-1 (with 8.2% Fe ratio), and FexOy@SBA-15-2 (with 16.3% Fe ratio) aggregate blocks, respectively. Parts a and b of Figure 1B show the low-angle XRD patterns of calcined rice grain-like SBA-15 silica particles (SBA-15-R) and FexOy@SBA-15-R (with 12.0% Fe ratio). The Fe weight ratios of these composites are determined by ICP analysis (Table 1). All the samples exhibit three well-resolved diffraction peaks that can be indexed as (100), (110), and (200) reflections associated with 2D hexagonal symmetry (P6mm), confirming a well-ordered mesoporous structure in the materials.10,11 The results indicate that the ordered hexagonal mesoporous structure of SBA-15 remain intact after the introduction of the FexOy layer. However, the intensities of these characteristic diffraction peaks become weaker with increasing amount of FexOy loaded, as shown in Figure 1A(b,c). This demonstrates that mesostructure was affected by loading FexOy, but the ordered hexagonal mesostructure was still kept. As shown in Figure 1A(d,e) and Figure 1B(c), each of the XRD patterns of IBU-FexOy@SBA15-1, IBU-FexOy@SBA-15-2, and IBU-FexOy@SBA-15-R shows only one (100) reflection. While the diffraction intensity decreased apparently upon loading with the drug, which showed that mesoporous phases were maintained, the integrity of the mesoporous structure was affected by the loading of the drug. Figure 2 shows the wide-angle XRD patterns of the corresponding samples. In Figure 2, the broad band centered at 2θ ) 22° can be assigned to the characteristic reflection from amorphous SiO2 (JCPDS 29-0085). The broad nature of the XRD patterns can be ascribed to the ultrasmall size of iron oxide.8 We excluded the existence of R-Fe2O3 on the basis of a comparison with sample d (R-Fe2O3@SBA-15-3) calcined at 600 °C. This sample show the peaks at 33.1°, 62.4°, and 64.0° (JCPDS 330664). The sharpened spinel (311) and (440) peaks at 35.5° and 62.9° were identified. Because of the similar peaks of γ-Fe2O3 and Fe3O4 (JCPDS 39-1346 and 79-0416), it is hard to distinguish the two iron oxides. First, the iron oxide loaded samples have red-brown color (Figure 10), which is the characteristic for γ-Fe2O3. To further confirm the existence of γ-Fe2O3 on the surface of SBA-15, these samples were subjected to XPS, which is a powerful tool for qualitatively determining the surface composition of a material. As shown in the XPS spectra for Fe (Figure 3), the binding energies at about 711 eV can be assigned to the 2p3/2 of Fe3+ ions in γ-Fe2O3.14 The lack
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Figure 1. (A) Low-angle XRD patterns of calcined aggregate blocks of SBA-15 (a), FexOy@SBA-15-1 (b), FexOy@SBA-15-2 (c), IBU-FexOy@SBA15-1 (d), and IBU-FexOy@SBA-15-2 (e). (B) Low-angle XRD patterns of calcined rice grain-like particles of SBA-15 (a), FexOy@SBA-15-R (b), and IBU-FexOy@SBA-15-R (c).
TABLE 1: Textural Parameters of the Calcined SBA-15, FexOy@SBA-15-1, and FexOy@SBA-15-2 Aggregate Blocks and Calcined Rice Grain-like SBA-15 and FexOy@SBA-15-R Particles samples
Dpore (nm)
pore volume (cm3/g)
SBET (m2/g)
SBA-15 (blocks) FexOy@SBA-15-1 IBU-FexOy@SBA-15-1 FexOy@SBA-15-2 IBU-FexOy@SBA-15-2 SBA-15-R (particles) FexOy@SBA-15-R IBU-FexOy@SBA-15-R
4.85 5.11 5.77 5.44 5.79 6.20 6.41 6.74
0.99 0.90 0.43 0.69 0.39 1.36 1.05 0.69
821 708 296 509 270 877 655 426
of the evident shoulder around 709 eV, characteristic of the 2p3/2 of Fe2+ ions, suggests that the Fe3O4 phase is in a very
IBU loading (%)
Fe loading (%) 8.2
29 16.3 26 22
12.0
low concentration, if there is any. In addition, the observable 2p3/2 satellite of the Fe3+ ions around 719 eV also supports the
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Figure 2. Wide-angle XRD patterns of FexOy@SBA-15-1 (a), FexOy@SBA-15-2 (b), FexOy@SBA-15-R (c), and R-Fe2O3@SBA-15-3 (d).
Figure 3. XPS spectra of FexOy@SBA-15-1 (a), FexOy@SBA-15-2 (b), and FexOy@ SBA-15-R (c).
above conclusion. Therefore, on the basis of XRD and XPS analysis, the as-prepared FexOy nanoparticles are mainly composed of γ-Fe2O3. 3.2. SEM and TEM Analysis. Figure 4a shows the SEM images of calcined classical SBA-15 samples, which are aggregate blocks of rodlike particles with size of 0.5 µm diameter and 1 µm length, agreeing well with those reported previously.15 Figure 4b reveals that the composites remain the same morphology as the classical SBA-15 after loading of FexOy. Figure 4c shows the images FexOy@SBA-15-R with an morphology of well-dispersed rice grain-like particles. The samples conserved the regularity and monodispersity of the original SBA-15 silica particles after the formation of FexOy nanoparticles.11 Figure 5 shows the TEM images of calcined classical SBA-15 [(a) perpendicular to the pore axis, (b) parallel to the pore axis] and FexOy@SBA-15-1 [(c) perpendicular to the pore axis, (d) parallel to the pore axis]. The TEM images of SBA15 exhibit the highly ordered hexagonal arrays of mesoporous channels, confirming a hexagonal (P6mm) mesostructure (Figure 5a,b). As shown in Figure 5c, FexOy can be observed as black dots existing on the surface of SBA-15. In Figure 5d, black dots distributed within the channels of SBA-15, while these dots cannot be seen in pure SBA-15 (Figure 5a,b). After the formation of FexOy, the regular arrays are still kept no matter observed from the direction parallel or perpendicular to the channels. We ascertain that part of FexOy filled inside the channels of the matrix and some dispersed on the surface of SBA-15, which can be further proved by the N2 adsorption/ desorption. Figure 5e,f shows the rice grain-like SBA-15 particles conserved their regular mesostructure before and after introduction of FexOy. The black FexOy dots can be seen on the surface and along the mesoporous channels in the rice grainlike SBA-15 materials after FexOy loading. 3.3. N2 Adsorption/Desorption. Figure 6A,B shows the N2 adsorption/desorption isotherms of classical SBA-15 (a), FexOy@SBA-15-1 (b), and FexOy@SBA-15-2 (c) and the
Figure 4. SEM images of the calcined classical SBA-15 (a) and FexOy@SBA-15-1 (b) aggregate blocks and FexOy@SBA-15-R (c) rice grain-like particles.
corresponding pore size distribution curves. It is known from the Table 1 that calcined classical SBA-15 has a high BET surface area (821 m2 g-1), a large pore volume (0.99 cm3 g-1), and pore size (4.85 nm). For FexOy@SBA-15-1, the BET surface area and pore volume are 708 m2 g-1 and 0.90 cm3 g-1, respectively. The decreased porous volume and specific surface area are not enough to prove that FexOy particles have grown inside the pores. As can be seen in Figure 6A, the classical SBA-15 shows typical IV isotherms with H1 hysteresis loop close near P/P0 ) 0.50, together with a narrow size distribution (Figure 6B), indicating a typical mesoporous material with hexagonal cylindrical channels.10 For FexOy@SBA-15, the shape of the isotherm is different from the pure SBA-15. A two-step behavior is observed on the hysteresis loop. The remaining empty mesopores behave like cylindrical mesopores with a hysteresis at higher relative pressure (P/P0 ) 0.50), whereas partially blocked mesopores are associated with a hysteresis loop close near P/P0 ) 0.40. As indicated in the previous literature,16 these two steps indicate that large oxide particles have grown in the pores of the silica host, yielding a typical ink-bottle
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Figure 6. (A) N2 adsorption/desorption isotherms for calcined classical aggregate blocks of SBA-15 (a), FexOy@SBA-15-1 (b), FexOy@SBA15-2 (c), IBU-FexOy @SBA-15-1 (d), and IBU-FexOy@SBA-15-2 (e). (B) Pore size distribution of above samples: SBA-15 (a), FexOy@SBA15-1 (b), IBU-FexOy@SBA-15-2 (c), IBU-FexOy@SBA-15-1 (d), and IBU-FexOy@SBA-15-2 (e).
Figure 5. TEM images of calcined classical aggregate blocks of SBA15 [(a) perpendicular to the pore axis, (b) parallel to the pore axis] and FexOy@SBA-15-1 [(c) perpendicular to the pore axis, (d) parallel to the pore axis], rice grain-like SBA-15 (e), and FexOy@SBA-15-R particles (f).
adsorption/desorption behavior. Several particles are located in the same mesopore, and the volume trapped between them can only be probed through small necks. It is interesting to see that the pore size distribution of the classical FexOy@SBA-15 change into two separate peaks: one remains the same range as the host material while the other moved to a smaller part. This can be ascribed to the FexOy nanoparticles generated on the outlet of silica grains plugging the mesopore entrance and located inside the mesopores, making them inaccessible to nitrogen molecules. After drug loading, the surface area and pore volume decreased to 296 m2 g-1 and 0.43 cm3 g-1, respectively. This can be a proof that ibuprofen has been adsorbed into the pores of FexOy@SBA-15-1. With higher FexOy loading grade, the FexOy@SBA-15-2 shows decreased BET surface area (509 m2 g-1) and pore volume (0.69 cm3 g-1). The BET surface area and pore volume decreased further to 270 m2 g-1 and 0.39 cm3 g-1 after IBU loading. Figure 7A shows the N2 adsorption/desorption isotherms of rice grain-like SBA-15 and FexOy@SBA-15-R particles. After the introduction of FexOy, the hysteresis loop becomes broader. The desorption branch of the isotherm shifts to lower pressure, the hysteresis loop end near P/P0 ) 0.40, while the rice grainlike SBA-15 silica shows typical IV isotherms with H1 hysteresis loop close near P/P0 ) 0.60. As suggested by Ravikovitch and co-workers, this behavior indicates the coexistence of open and partially closed mesopores.17 For the rice grain-
Figure 7. (A) N2 adsorption/desorption isotherms for calcined rice grain-like particles of SBA-15 silica (a), FexOy@SBA-15-R (b), and IBU-FexOy@SBA-15-R (c). (B) Pore size distribution of above samples: SBA-15 silica (a), FexOy@SBA-15-R (b), and IBUFexOy@SBA-15-R (c).
like SBA-15 silica particles, the BET surface (877 m2 g-1) and pore volume (1.36 cm3 g-1) decreased to 655 m2 g-1 and 1.05
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Figure 9. Magnetization as a function of applied magnetic field measured at 300 K: (a) FexOy@SBA-15-1, (b) FexOy@SBA-15-2, and (c) FexOy@SBA-15-R.
Figure 8. (A) FT-IR spectra of calcined SBA-15 (a), FexOy@SBA15-1 (b), FexOy@SBA-15-2 (c), and FexOy@SBA-15-R (d). (B) FT-IR spectra of FexOy@SBA-15-1 (a), IBU-FexOy@SBA-15-1 (b), IBUFexOy@SBA-15-2 (c), IBU-FexOy@SBA-15-R (d), and ibuprofen (e).
cm3 g-1 after the introduction of FexOy. After the loading of IBU, the BET surface area and pore volume of FexOy@SBA15-R decreased to 426 m2 g-1 and 0.69 cm3 g-1, respectively. It can be concluded that all the mesoporous samples possess high adsorption capability as drug carriers for the drug targeting system. 3.4. FT-IR Spectra. Figure 8 shows IR spectra of samples before and after IBU adsorption. The spectrum of SBA-15 exhibited bands assigned to silica and adsorbed water at 3420 cm-1 (the O-H stretching of adsorbed water and the hydrogenbonded silanol groups), 1640 cm-1 (the O-H bending of adsorbed water), 1083 cm-1(the Si-O asymmetrical stretching of siloxane), 970 cm-1 (the Si-OH bending), and 800 cm-1 (in-plane bending of geminal silanol).18 A new band at 563 cm-1 assigned to the Fe-O vibration was observed in the spectra profiles of FexOy@SBA-15-2 and FexOy@SBA-15-R with higher FexOy amount in the silica host.5b The Si-OH band at 3744 cm-1 in the mesoporous silica material is still kept in the FexOy@SBA-15-1 and FexOy@SBA-15-R with low FexOy loading amount, while it disappears in the profiles of FexOy@ SBA-15-2 with higher Fe ratio and after ibuprofen loading onto these composites. The intensity of the Si-OH band at 970 cm-1 present in as-prepared SBA-15 silica decreases after the loading of FexOy. This can be ascribed to the interaction between the FexOy and Si-OH, which may form the Fe-O-Si bond. After the adsorption of ibuprofen, the Si-OH band almost disappears. The intensities of COOH at 1722 cm-1 of ibuprofen decreased significantly. Meanwhile, a new peak at 1595 cm-1 is clearly observed. This peak may be attributed to the asymmetric stretching vibration of COO-, since carboxylic acid salts exhibit a strong characteristic COO- asymmetric stretching band in the range of 1650-1550 cm-1.19 This observation is different from those previous reports on functionalized SBA-15 without FexOy, in which a new peak at 1558 cm-1 ascribed to the asymmetric stretching vibration of COO- was found.20 This can be explained
Figure 10. Photograph of the composites in the presence of the magnetic field.
by the coexistence of interaction between COOH and Fe-O, which may form the COO-Fe bond. The presence of the COOH at 1722 cm-1, the ternary carbon atom peaks at 1463 cm-1, and the C-Hx peaks at 2931 and 2957 cm-1 21 suggests that a certain amount of ibuprofen molecules, which do not form any bonding on pore channels, has been stored in the cores. These results can be a proof that the ibuprofen has been incorporated into these composites. 3.5. Magnetic Properties. The magnetic properties of FexOy loaded SBA-15 composites were characterized using a superconducting quantum interference device (SQUID) magnetometer with fields of up to 5 T. The hysteresis loops of these samples were registered at temperatures of 300 K. The field-dependent magnetization plots illustrate these samples are superparamagnetic at 300 K. The magnetization curves at 300 K show no hysteresis (Figure 9), which means that these composites exhibit superparamagnetic behavior at room temperature. Such behavior is believed to be derived from the γ-Fe2O3 nanoparticles formed in the SBA-15 host silicas. Superparamagnetic particles have a great potential for the drug targeting, as it can be attracted to a magnetic field but retain no residual magnetism after the field is removed. The saturation magnetization of these samples is 2.47 emu g-1 (FexOy@SBA-15-1), 2.97 emu g-1 (FexOy@SBA15-R), and 3.49 emu g-1 (FexOy@SBA-15-2).8,22 All of these composites show sufficient response to the external magnetic field, as shown in Figure 10. The saturation magnetization increased with the increasing amount of γ-Fe2O3 generating in the silica matrix. Thus, we can regulate the FexOy loading amount to obtain composites with different magnetization properties. 3.6. Drug Adsorption and in Vitro Release. The respective loading degrees of IBU for FexOy@SBA-15-1, FexOy@SBA-
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Figure 11. (A) TG curves of FexOy@SBA-15-1 (a), FexOy@SBA15-2 (b), FexOy@SBA-15-R (c), IBU-FexOy@SBA-15-1 (d), IBUFexOy@SBA-15-2 (e), and IBU-FexOy@SBA-15-R (f). (B) DTA curves of FexOy@SBA-15-1 (a), FexOy@SBA-15-2 (b), FexOy@SBA-15-R (c), IBU-FexOy@SBA-15-1 (d), IBU-FexOy@SBA-15-2 (e), and IBUFexOy@SBA-15-R (f).
Figure 12. Cumulative release rate of IBU-FexOy@SBA-15-1 (a), IBU-FexOy@SBA-15-2 (b), and IBU-FexOy@SBA-15-R (c).
15-2, and FexOy@SBA-15-R are 29, 26, and 22 wt %, respectively, determined by TG analysis (Figure 11A). Figure 11B displays DTA curves of FexOy@SBA-15-1, FexOy@SBA15-2, FexOy@SBA-15-R, and IBU-FexOy@SBA-15-1, IBUFexOy@SBA-15-2, IBU-FexOy@SBA-15-R. The low-temperature endothermic peaks around 80-100 °C can be assigned to the loss of water molecules. The exotherm Ix (∼240 °C), IIx (∼340 °C) associated with the loss of ibuprofen were observed in the IBU loaded composites, which was bare in the FexOy@SBA-15 samples. Figure 12 shows the cumulative release of IBU of the three systems in simulated body fluids. The IBU-FexOy@SBA-15-R system exhibits 22.50 wt % drugpronounced initial burst release with in 2 h, while the amount
Huang et al. of drug release from IBU-FexOy@SBA-15-1 and IBUFexOy@SBA-15-2 systems was 11.76 and 15.12 wt % within 2 h, respectively. The initial burst release could be caused by the ibuprofen molecules physically adsorbed on the surface of the composites and near the entrance of the channels. The drug stored in the channels and the cores dissolved after the long time penetrating of the medium and diffused along aqueous pathways into the medium. As shown in Figure 12, all of the IBU release from FexOy@SBA-15-R within 24 h, while it took 48 h to release nearly all the IBU from the FexOy@SBA-15-1 and FexOy@SBA-15-2 samples. The higher release rate of the IBU-FexOy@SBA-15-R can be ascribed to its larger pore size and shorter pathway caused by the smaller particle size. As for FexOy@SBA-15-1 and FexOy@SBA-15-2, the nature of the pore wall surface seems to play a key role for drug adsorption and delivery.23 The difference in delivery rate due to driving force for the ibuprofen inside the channels seems to be the hydrogen bond interaction between the drug molecules and the silanol groups. As can be seen from the FT-IR results, the intensities of the Si-OH bands on the surface of SBA-15 decrease after the introduction of FexOy, which means weaker interaction between drug and Si-OH bands. Though COO-Fe bond may form, the intensity of the bonding was weaker because of its low quantity compared with the hydrogen bonding. So the release of ibuprofen from FexOy@SBA-15-1 is slower than those from FexOy@SBA-15-2. From the above results, it can be confirmed that all the samples possess capability as drug carriers for targeting system. The release profiles can be regulated by choosing the composites possessing specific properties, which will be useful for clinical cases demanding appropriate dosage. 4. Conclusions In this paper, we synthesized magnetic FexOy@SBA-15 composites with different morphologies by a sol-gel method. These obtained magnetic composites conserve ordered mesoporous structure and show high surface area and pore volume after the formation of FexOy nanoparticles. These FexOy nanoparticles were mainly composed of γ-Fe2O3, which contributed to the superparamagnetic properties of FexOy@SBA-15 composites. The saturation magnetization of these composites changed with the regulating of loading amount of γ-Fe2O3. All of these composites show sufficient response to the external magnetic field, which can be used as carriers in drug delivery system to reach targeted location under external magnetic field. The storage capacity and in vitro release profiles of ibuprofen were investigated. All the systems exhibit sustained-release profiles. Magnetic rice grain-like SBA-15 composites possessing regular morphology show higher release rate compared with FexOy loaded classical SBA-15 blocks. The release rate is affected by the pore size, particle morphology, and surface property of these systems. Acknowledgment. This project is financially supported by the foundation of “Bairen Jihua” of Chinese Academy of Science, the MOST of China (2003CB314707, 2007CB935502), and the National Natural Science Foundation of China (NSFC 50572103, 20431030, 00610227). We thank Mr. Lin Xu (Northeast Normal University, Changchun) for valuable help with the SQUID measurements. References and Notes (1) (a) Nasongkla, N.; Bey, E.; Ren, J.; Ai, H.; Khemtong, C.; Guthi, J. S.; Chin, S. F.; Sherry, A. D.; Boothman, D. A.; Gao, J. Nano Lett. 2006, 6, 2427. (b) Wang, D.; He, J.; Rosenzweig, N.; Rosenzweig, Z. Nano Lett. 2004, 4 (3), 409. (c) Mornet, S.; Vasseur, S.; Grasnet, F.; Duguet, E. J.
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