- Email: [email protected]
calcium silicate nanocomposites
Materials Letters 104 (2013) 53–56
Contents lists available at SciVerse ScienceDirect
Materials Letters journal homepage: www.elsevier.com/locate/matlet
Synthesis and application in drug delivery of hollow-core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposites Bing-Qiang Lu, Ying-Jie Zhu n, Guo-Feng Cheng, Yin-Jie Ruan State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China
art ic l e i nf o
a b s t r a c t
Article history: Received 5 February 2013 Accepted 2 April 2013 Available online 10 April 2013
Nanocomposites with magnetic iron oxide as the hollow core, silica as the middle shell and calcium silicate as the outer shell are the ideal agent for application in medical diagnosis and therapy. In this paper, by sol–gel coating the self-assembled nanoparticles of magnetic iron oxide with silica, then reacting with Ca(NO3)2 4H2O at 600 1C in inert N2 atmosphere, the nanocomposite consisting of hollowcore-double-shell magnetic iron oxide/silica/calcium silicate has been successfully synthesized. The components of the hollow core, middle layer and outer layer are Fe3O4, SiO2, CaSiO4, respectively. The nanocomposite has a superparamagnetic behavior and good drug delivery performance, which are promising for the application in targeted drug delivery. & 2013 Published by Elsevier B.V.
Keywords: Biomaterials Nanocomposites Iron oxide Silica Calcium silicate Drug delivery
1. Introduction Nanoscience and nanotechnology researches are gradually shifting from the individual component to hybrid nanostructured materials, especially to the complex nanocomposites. In general, the nanocomposites show novel properties and multifunctions. Among various nanocomposites, the core–shell nanocomposites have been subject to extensive studies in the past years. Most of them consist of a solid core and a single-shell [1–3]. Few reports have been involved in more complex core–shell nanocoposites with multi-cores [4,5], multi-shells [6–9] or hollow-core [10–12] due to their complicated synthesis methods. The hollow-coremulti-shell nanocomposites (HCMSN), which contain a hollow core and multi-shells with different components, have attracted much attention in the past years. Wu et al. [10] synthesized the HCMSN with a hollow Fe3O4 core, a mesoporous SiO2 layer and mixed organic layer. Zhu et al. [11] prepared hollow mesoporous silica sphere/polyelectrolyte multilayer HCMSN with stimuliresponsive controlled drug release using a LBL method. Wang et al. [12] prepared hollow spheres with multi-shells of SiO2, TiO2 and polyaniline (PAN). However, up to date still very little work has been done on the synthesis and application of the HCMSN. Magnetic iron oxide (MIO) and calcium silicate (CS) are of the most important inorganic biomaterials. MIO has the magnetic behavior which can be used in magnetic targeting, magnetic resonance imaging, and hyperthermia agent. CS has excellent
n
Corresponding author. Tel.: +86 21 52412616; fax: +86 21 52413122. E-mail address: [email protected] (Y.-J. Zhu).
0167-577X/$ - see front matter & 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.matlet.2013.04.005
bioactivity and biodegradability comparing with other inorganic biomaterials such as Au and silica, and has provided the great avenue for the applications in bone repair and drug delivery [13,14]. Thus the MIO/CS core–shell nanocomposites with CS coating MIO are the ideal agent in medical diagnosis and therapy. However, the typical sheet-like structure of CS prepared by conventional methods makes it difficult to coat on the cores with a closed shell. According to a previous report, CS nanospheres could be prepared using silica as the template at high temparature [15]. Besides, magnetic iron oxide could be easily coated by silica [16]. Herein, by coating the magnetic iron oxide with silica, reacting with Ca(NO3)2 4H2O at 600 1C for 12 h in the inert N2 atmosphere, we have synthesized hollow-core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposites (MSCN). In the nanocomposites, the hollow MIO nanospheres constructed by selfassembly of nanoparticles are encapsulated by a layer of SiO2, and then by a layer of CS successively. The as-synthesized MSCN have a superparamagnetic behavior and good drug delivery performance. 2. Experimental MIO nanoparticles were synthesized using a previously reported method with a minor modification [17]. FeCl3 6H2O (1.080 g), sodium citrate dihydrate (0.200 g), and sodium acetate (NaAc, 1.200 g) were dissolved in ethylene glycol (20.0 mL) with magnetic stirring, the resulting solution was transferred to a Teflon-lined stainless-steel autoclave and heated at 210 1C for
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B.-Q. Lu et al. / Materials Letters 104 (2013) 53–56
10 h. The black product was washed with deionized water and ethanol for several times and dispersed in 50 mL of ethanol. MIO/SiO2 nanoparticles was synthesized by coating the MIO nanoparticles with SiO2 via a sol–gel method. 10 mL of aforementioned MIO nanoparticles-ethanol dispersion, 7 mL of NH3 H2O and 0.2 mL of tetraethyl orthosilicate (TEOS) were added into 75 mL of ethanol. Then the mixture was treated with pulsed ultrasonic wave for 90 min using a high-intensity ultrasonic probe (Ti-horn, 20 kHz). The products were washed with ethanol for several times and dispersed in 10 mL of ethanol for further use. MSCN were prepared by partially transforming SiO2 layer to calcium silicate (CS), according to a previous report with a minor modification [15]. 0.260 g of Ca(NO3)2 4H2O was dissolved in the Fe3O4/SiO2 nanoparticles-ethanol dispersion under ultrasonic. Then the mixture was dried in a forced air oven at the temperature lower than 40 1C to evaporate the ethanol. The obtained viscous mixture was transferred to a quartz boat and heated in a tube furnace in flowing nitrogen gas to 600 1C with a heating rate of 1 1C/min and held at 600 1C for 12 h. The product was then washed with deionized water for several times to remove the unreacted CaO. The MSCN synthesized by heated for 12 h at 600 1C were used as the drug nanocarrier. The ibuprofen was used as a model drug. 0.160 g of MSCN were dispersed in 100 mL of ibuprofen-
hexane dispersion with the ibuprofen concentration of 40 mg/mL. The resulting solution was then sealed immediately, oscillated with a constant rate of 140 rpm at 37 1C for 24 h. The drug-loaded MSCN were separated by centrifugation and dried at 37 1C. 0.130 g of the drug-loaded MSCN were used to study the drug release behavior, which was compacted into a disk with a diameter of 10 mm at the pressure of 4 MPa. The disk was immersed into 100 mL phosphate buffer saline (PBS, pH¼ 7.4) at 37 1C under shaking at a constant rate of 140 rpm. At given time intervals, 2 mL of the drug release medium was extracted for UV–vis absorption analysis at the wavelength of 264 nm, and 2 mL of fresh PBS was added into the release system to keep the the same volume of release medium.
3. Results and discussion The typical synthesis process of the nanocomposite is shown in Fig. 1a. First, with the aid of ultrasound, SiO2 was coated on the solid MIO nanospheres by a sol–gel method in ethanol using TEOS as the Si source to obtain the solid-core-single-shell MIO/SiO2 nanospheres. Then the ethanol suspension containing solid-coresingle-shell MIO/SiO2 nanospheres was mixed with Ca(NO3)2 4H2O, and ethanol was evaporated. After heating at 600 1C for
Fig. 1. (a) Illustration of the main strategy for the preparation of the MSCN. (b) TEM micrograph of as–prepared MIO nanospheres constructed by self–assembly of nanoparticles. (c–e) TEM micrographs of as–prepared MSCN obtained by heating silica coated MIO nanospheres with Ca(NO3)2 4H2O at 600 1C for different times: (c) 12 h, (d) 5 h, and (e) 3 h.
B.-Q. Lu et al. / Materials Letters 104 (2013) 53–56
55
Fig. 2. (a) TEM micrograph of a single MSCN obtained by heating silica coated MIO nanospheres with Ca(NO3)2 4H2O at 600 1C for 12 h, (b) atomic percentages measured at different sites of a single MSCN shown in (a). The numbers (I, II, III) correspond to the sites marked by arrows in (a).
Fig. 3. (a) XRD patterns of the MSCN synthesized at 600 1C for different heating times: (I) 12 h, and (II) 3 h; (b) magnetic hysteresis loop of the MSCN synthesized by heating at 600 1C for 12 h; (c) the reversible magnetic separation–redispersion processes of the MSCN in aqueous solution.
12 h in an inert N2 atmosphere, CaO, which was formed by the decomposition of Ca(NO3)2 4H2O [18], reacted with SiO2 to form a CS layer on MIO/SiO2 nanospheres. In this way, the hollow-coredouble-shell magnetic iron oxide/silica/calcium silicate nanocomposites were obtained. The morphology of the as-synthesized MSCN was investigated with transmission electron microscopy (TEM). The TEM micrograph in Fig. 1b shows that the as-synthesized MIO consisted of solid nanospheres constructed by self-assembly of nanoparticles. After coating with silica and reacting with Ca(NO3)2 4H2O at 600 1C in N2 atmosphere for 12 h, the hollow-core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposites were obtained (Fig. 1c). The average diameter of MSCN, the diameter of the core and the thickness of the coating layer (silica and CS) were about 300 nm, 200 nm and 50 nm. The X-ray energy dispersive spectra (EDS) showed the presence of CS. EDS data at different sites of a single MSCN were also measured, implying the component of the outer layer was Ca2SiO4, and the middle layer was SiO2 (Fig. 2b). The influence of the heating time at 600 1C on the morphology of the MSCN was studied. As discussed above, the hollow-
core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposite was obtained when the heating time was 12 h (Fig. 1c). When the heating time was shortened to 5 h, the morphology was similar to that of the sample obtained by heating for 12 h, indicating that the hollow-core-double-shell nanocomposite formed within 5 h of heating time (Fig. 1d). However, the cores were solid when the heating time was reduced to 3 h (Fig. 1e), implying that the formation of asprepared hollow core of the MSCN should be a result of the Oswald ripening process. EDS data also showed the presence of CS in the samples obtained by 3 h and 5 h heating. The amount of Ca(NO3)2 4H2O also influences the morphology of the MSCN. As discussed above, the hollow-core-doubleshell magnetic iron oxide/silica/calcium silicate nanocomposite was obtained when Ca(NO3)2 4H2O was 0.260 g (Fig. 1c). When Ca(NO3)2 4H2O was doubled while other experimental conditions were kept the same, the coating layer was broken and dropped off in some cases. Fig. 3a displays the X-ray powder diffraction (XRD, Cu Kα, λ¼ 1.54178 Å) patterns of the MSCN synthesized at 600 1C for different heating times. The MSCN synthesized for 12 h consisted
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Fig. 4. (a) TG curves of as–synthesized MSCN without drug (I) and the ibuprofen–loaded MSCN (II). (b) Ibuprofen release profile of the drug loaded MSCN in PBS.
of mixed crystal phases of Fe3O4 (JCPDS 19–0629) and Ca2SiO4 (JCPDS 23–1042). The Fe3O4 phase was from the used MIO nanoparticles as the core for the MSCN preparation, and accounts for the magnetic performance of the product. The atomic ratio of Ca and Si of Ca2SiO4 is consistent with that of the outer layer obtained by the EDS analysis (about 2:1), verifying that the outer layer is Ca2SiO4 and the middle layer is SiO2. Because of its amorphous structure of SiO2, the diffraction peaks of SiO2 were not observed. When the heating time was shortened to 3 h, the diffraction peaks corresponding to Ca2SiO4 were weak due to its poor crystallinity. We can infer from the experimental results that poorly crystallized CS is formed after the reaction between CaO (formed from the decomposition of calcium nitrate) and SiO2 for 3 h heating time, and the crystallinity of CS increased with the heating time. Fig. 3b shows the magnetic hysteresis loop of the MSCN synthesized by heating at 600 1C for 12 h. The MSCN had a superparamagnetic behavior, which should be contributed by the Fe3O4 core of the MSCN. The saturation magnetization was 6.0 emu/g. When a external magnet was applied, the MSCN could be separated from their dispersion rapidly in less than 3 min, while dispersed again if shaking slightly after withdrawing the magnet (Fig. 3c), indicating a good magnetic response and dispersibility. Because of the excellent drug loading capacity of calcium silicate [14], the as-synthesized MSCN was explored as the drug carrier in this work. Ibuprofen was used as a model drug. The drug loading capacity was measured to be 75 mg drug/g carrier. Fig. 4b shows the ibuprofen drug release profile of the drug loaded MSCN in phosphate buffer saline (PBS) at 37 1C. One can see that the loaded ibuprofen in the MSCN continuously released in a period of 60 h. The release of loaded ibuprofen was rapid in the first 5 h, then gradually slowed down, and the drug release was almost complete at a release time of 60 h. Considering the combined advantages of both sustained drug release and magnetic behavior, the as-synthesized MSCN has the potential application in targeted drug delivery. 4. Conclusions In summary, we have developed a method for synthesizing the hollow-core-double-shell magnetic iron oxide/silica/calcium
silicate nanocomposites. The components of hollow core, middle layer and outer layer are Fe3O4, SiO2, Ca2SiO4, respectively. The hollow core of the MSCN forms at 600 1C within 5 h of heating time by the Oswald ripening process. The poorly crystallized CS layer is formed within 3 h of heating time at 600 1C, and the crystallinity increases with the heating time. The MSCN has a drug loading capacity of 75 mg/g, and the drug can be completely released in a time period of 60 h. The as–prepared MSCN is promising for the potential application in targeted drug delivery.
Acknowledgments This work was supported by the National Basic Research Program of China (973 Program, No. 2012CB933600), the National Natural Science Foundation of China (51172260, 51121064) and the Science and Technology Commission of Shanghai (11nm0506600).
References [1] Deng C, Deng Y, Qi D, Zhang X, Zhao D. J Am Chem Soc 2008;130:28–9. [2] Jin YD, Jia CX, Huang SW, O’Donnell M, Gao XH. Nat Commun 2010;1: Art. No. 41. [3] Liu GX, Peng HX, Dong XT, Wang JX, Xu J, Yu WS. J Alloy Compd 2011;509:6930–4. [4] Trongsatitkul T, Budhlall BM. Langmuir 2011;27:13468–80. [5] Chang BS, Zhang XR, Guo J, Sun Y, Tang HY, Ren QG, et al. J Colloid Interf Sci 2012;377:64–75. [6] Yec CC, Zeng HC. Chem Mater 2012;24:1917–29. [7] Xu C, Qiu T, Deng JQ, Meng Y, He LF, Li XY. Prog Org Coat 2012;74:233–9. [8] Thierry R, Perillat–Merceroz G, Jouneau PH, Ferret P, Feuillet G. Nanotechnology 2012;23:85705–10. [9] Wong YJ, Zhu LF, Teo WS, Tan YW, Yang YH, Wang C, et al. J Am Chem Soc 2011;133:11422–5. [10] Wu HX, Zhang SJ, Zhang JM, Liu G, Shi JL, Zhang LX, et al. Adv Funct Mater 2011;21:1850–62. [11] Zhu YF, Shi JL, Shen WH, Dong XP, Feng JW, Ruan ML, et al. Angew Chem Int Ed 2005;44:5083–7. [12] Wang DP, Zeng HC. Chem Mater 2009;21:4811–23. [13] Liu XY, Morra M, Carpi A, Li B. Biomed Pharmacother 2008;62:526–9. [14] Wu J, Zhu YJ, Cao SW, Chen F. Adv Mater 2010;22:749–53. [15] Kang XJ, Huang SS, Yang PP, Ma PA, Yang DM, Lin J. Dalton Trans 2011;40:1873–9. [16] Liu J, Qiao SZ, Hu QH, Lu GQ. Small 2011;7:425–43. [17] Liu J, Sun ZK, Deng YH, Zou Y, Li CY, Guo XH, et al. Angew Chem Int Ed 2009;48:5875–9. [18] Brockner W, Ehrhardt C, Gjikaj M. Thermochim Acta 2007;456:64–8.
Contents lists available at SciVerse ScienceDirect
Materials Letters journal homepage: www.elsevier.com/locate/matlet
Synthesis and application in drug delivery of hollow-core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposites Bing-Qiang Lu, Ying-Jie Zhu n, Guo-Feng Cheng, Yin-Jie Ruan State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China
art ic l e i nf o
a b s t r a c t
Article history: Received 5 February 2013 Accepted 2 April 2013 Available online 10 April 2013
Nanocomposites with magnetic iron oxide as the hollow core, silica as the middle shell and calcium silicate as the outer shell are the ideal agent for application in medical diagnosis and therapy. In this paper, by sol–gel coating the self-assembled nanoparticles of magnetic iron oxide with silica, then reacting with Ca(NO3)2 4H2O at 600 1C in inert N2 atmosphere, the nanocomposite consisting of hollowcore-double-shell magnetic iron oxide/silica/calcium silicate has been successfully synthesized. The components of the hollow core, middle layer and outer layer are Fe3O4, SiO2, CaSiO4, respectively. The nanocomposite has a superparamagnetic behavior and good drug delivery performance, which are promising for the application in targeted drug delivery. & 2013 Published by Elsevier B.V.
Keywords: Biomaterials Nanocomposites Iron oxide Silica Calcium silicate Drug delivery
1. Introduction Nanoscience and nanotechnology researches are gradually shifting from the individual component to hybrid nanostructured materials, especially to the complex nanocomposites. In general, the nanocomposites show novel properties and multifunctions. Among various nanocomposites, the core–shell nanocomposites have been subject to extensive studies in the past years. Most of them consist of a solid core and a single-shell [1–3]. Few reports have been involved in more complex core–shell nanocoposites with multi-cores [4,5], multi-shells [6–9] or hollow-core [10–12] due to their complicated synthesis methods. The hollow-coremulti-shell nanocomposites (HCMSN), which contain a hollow core and multi-shells with different components, have attracted much attention in the past years. Wu et al. [10] synthesized the HCMSN with a hollow Fe3O4 core, a mesoporous SiO2 layer and mixed organic layer. Zhu et al. [11] prepared hollow mesoporous silica sphere/polyelectrolyte multilayer HCMSN with stimuliresponsive controlled drug release using a LBL method. Wang et al. [12] prepared hollow spheres with multi-shells of SiO2, TiO2 and polyaniline (PAN). However, up to date still very little work has been done on the synthesis and application of the HCMSN. Magnetic iron oxide (MIO) and calcium silicate (CS) are of the most important inorganic biomaterials. MIO has the magnetic behavior which can be used in magnetic targeting, magnetic resonance imaging, and hyperthermia agent. CS has excellent
n
Corresponding author. Tel.: +86 21 52412616; fax: +86 21 52413122. E-mail address: [email protected] (Y.-J. Zhu).
0167-577X/$ - see front matter & 2013 Published by Elsevier B.V. http://dx.doi.org/10.1016/j.matlet.2013.04.005
bioactivity and biodegradability comparing with other inorganic biomaterials such as Au and silica, and has provided the great avenue for the applications in bone repair and drug delivery [13,14]. Thus the MIO/CS core–shell nanocomposites with CS coating MIO are the ideal agent in medical diagnosis and therapy. However, the typical sheet-like structure of CS prepared by conventional methods makes it difficult to coat on the cores with a closed shell. According to a previous report, CS nanospheres could be prepared using silica as the template at high temparature [15]. Besides, magnetic iron oxide could be easily coated by silica [16]. Herein, by coating the magnetic iron oxide with silica, reacting with Ca(NO3)2 4H2O at 600 1C for 12 h in the inert N2 atmosphere, we have synthesized hollow-core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposites (MSCN). In the nanocomposites, the hollow MIO nanospheres constructed by selfassembly of nanoparticles are encapsulated by a layer of SiO2, and then by a layer of CS successively. The as-synthesized MSCN have a superparamagnetic behavior and good drug delivery performance. 2. Experimental MIO nanoparticles were synthesized using a previously reported method with a minor modification [17]. FeCl3 6H2O (1.080 g), sodium citrate dihydrate (0.200 g), and sodium acetate (NaAc, 1.200 g) were dissolved in ethylene glycol (20.0 mL) with magnetic stirring, the resulting solution was transferred to a Teflon-lined stainless-steel autoclave and heated at 210 1C for
54
B.-Q. Lu et al. / Materials Letters 104 (2013) 53–56
10 h. The black product was washed with deionized water and ethanol for several times and dispersed in 50 mL of ethanol. MIO/SiO2 nanoparticles was synthesized by coating the MIO nanoparticles with SiO2 via a sol–gel method. 10 mL of aforementioned MIO nanoparticles-ethanol dispersion, 7 mL of NH3 H2O and 0.2 mL of tetraethyl orthosilicate (TEOS) were added into 75 mL of ethanol. Then the mixture was treated with pulsed ultrasonic wave for 90 min using a high-intensity ultrasonic probe (Ti-horn, 20 kHz). The products were washed with ethanol for several times and dispersed in 10 mL of ethanol for further use. MSCN were prepared by partially transforming SiO2 layer to calcium silicate (CS), according to a previous report with a minor modification [15]. 0.260 g of Ca(NO3)2 4H2O was dissolved in the Fe3O4/SiO2 nanoparticles-ethanol dispersion under ultrasonic. Then the mixture was dried in a forced air oven at the temperature lower than 40 1C to evaporate the ethanol. The obtained viscous mixture was transferred to a quartz boat and heated in a tube furnace in flowing nitrogen gas to 600 1C with a heating rate of 1 1C/min and held at 600 1C for 12 h. The product was then washed with deionized water for several times to remove the unreacted CaO. The MSCN synthesized by heated for 12 h at 600 1C were used as the drug nanocarrier. The ibuprofen was used as a model drug. 0.160 g of MSCN were dispersed in 100 mL of ibuprofen-
hexane dispersion with the ibuprofen concentration of 40 mg/mL. The resulting solution was then sealed immediately, oscillated with a constant rate of 140 rpm at 37 1C for 24 h. The drug-loaded MSCN were separated by centrifugation and dried at 37 1C. 0.130 g of the drug-loaded MSCN were used to study the drug release behavior, which was compacted into a disk with a diameter of 10 mm at the pressure of 4 MPa. The disk was immersed into 100 mL phosphate buffer saline (PBS, pH¼ 7.4) at 37 1C under shaking at a constant rate of 140 rpm. At given time intervals, 2 mL of the drug release medium was extracted for UV–vis absorption analysis at the wavelength of 264 nm, and 2 mL of fresh PBS was added into the release system to keep the the same volume of release medium.
3. Results and discussion The typical synthesis process of the nanocomposite is shown in Fig. 1a. First, with the aid of ultrasound, SiO2 was coated on the solid MIO nanospheres by a sol–gel method in ethanol using TEOS as the Si source to obtain the solid-core-single-shell MIO/SiO2 nanospheres. Then the ethanol suspension containing solid-coresingle-shell MIO/SiO2 nanospheres was mixed with Ca(NO3)2 4H2O, and ethanol was evaporated. After heating at 600 1C for
Fig. 1. (a) Illustration of the main strategy for the preparation of the MSCN. (b) TEM micrograph of as–prepared MIO nanospheres constructed by self–assembly of nanoparticles. (c–e) TEM micrographs of as–prepared MSCN obtained by heating silica coated MIO nanospheres with Ca(NO3)2 4H2O at 600 1C for different times: (c) 12 h, (d) 5 h, and (e) 3 h.
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Fig. 2. (a) TEM micrograph of a single MSCN obtained by heating silica coated MIO nanospheres with Ca(NO3)2 4H2O at 600 1C for 12 h, (b) atomic percentages measured at different sites of a single MSCN shown in (a). The numbers (I, II, III) correspond to the sites marked by arrows in (a).
Fig. 3. (a) XRD patterns of the MSCN synthesized at 600 1C for different heating times: (I) 12 h, and (II) 3 h; (b) magnetic hysteresis loop of the MSCN synthesized by heating at 600 1C for 12 h; (c) the reversible magnetic separation–redispersion processes of the MSCN in aqueous solution.
12 h in an inert N2 atmosphere, CaO, which was formed by the decomposition of Ca(NO3)2 4H2O [18], reacted with SiO2 to form a CS layer on MIO/SiO2 nanospheres. In this way, the hollow-coredouble-shell magnetic iron oxide/silica/calcium silicate nanocomposites were obtained. The morphology of the as-synthesized MSCN was investigated with transmission electron microscopy (TEM). The TEM micrograph in Fig. 1b shows that the as-synthesized MIO consisted of solid nanospheres constructed by self-assembly of nanoparticles. After coating with silica and reacting with Ca(NO3)2 4H2O at 600 1C in N2 atmosphere for 12 h, the hollow-core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposites were obtained (Fig. 1c). The average diameter of MSCN, the diameter of the core and the thickness of the coating layer (silica and CS) were about 300 nm, 200 nm and 50 nm. The X-ray energy dispersive spectra (EDS) showed the presence of CS. EDS data at different sites of a single MSCN were also measured, implying the component of the outer layer was Ca2SiO4, and the middle layer was SiO2 (Fig. 2b). The influence of the heating time at 600 1C on the morphology of the MSCN was studied. As discussed above, the hollow-
core-double-shell magnetic iron oxide/silica/calcium silicate nanocomposite was obtained when the heating time was 12 h (Fig. 1c). When the heating time was shortened to 5 h, the morphology was similar to that of the sample obtained by heating for 12 h, indicating that the hollow-core-double-shell nanocomposite formed within 5 h of heating time (Fig. 1d). However, the cores were solid when the heating time was reduced to 3 h (Fig. 1e), implying that the formation of asprepared hollow core of the MSCN should be a result of the Oswald ripening process. EDS data also showed the presence of CS in the samples obtained by 3 h and 5 h heating. The amount of Ca(NO3)2 4H2O also influences the morphology of the MSCN. As discussed above, the hollow-core-doubleshell magnetic iron oxide/silica/calcium silicate nanocomposite was obtained when Ca(NO3)2 4H2O was 0.260 g (Fig. 1c). When Ca(NO3)2 4H2O was doubled while other experimental conditions were kept the same, the coating layer was broken and dropped off in some cases. Fig. 3a displays the X-ray powder diffraction (XRD, Cu Kα, λ¼ 1.54178 Å) patterns of the MSCN synthesized at 600 1C for different heating times. The MSCN synthesized for 12 h consisted
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Fig. 4. (a) TG curves of as–synthesized MSCN without drug (I) and the ibuprofen–loaded MSCN (II). (b) Ibuprofen release profile of the drug loaded MSCN in PBS.
of mixed crystal phases of Fe3O4 (JCPDS 19–0629) and Ca2SiO4 (JCPDS 23–1042). The Fe3O4 phase was from the used MIO nanoparticles as the core for the MSCN preparation, and accounts for the magnetic performance of the product. The atomic ratio of Ca and Si of Ca2SiO4 is consistent with that of the outer layer obtained by the EDS analysis (about 2:1), verifying that the outer layer is Ca2SiO4 and the middle layer is SiO2. Because of its amorphous structure of SiO2, the diffraction peaks of SiO2 were not observed. When the heating time was shortened to 3 h, the diffraction peaks corresponding to Ca2SiO4 were weak due to its poor crystallinity. We can infer from the experimental results that poorly crystallized CS is formed after the reaction between CaO (formed from the decomposition of calcium nitrate) and SiO2 for 3 h heating time, and the crystallinity of CS increased with the heating time. Fig. 3b shows the magnetic hysteresis loop of the MSCN synthesized by heating at 600 1C for 12 h. The MSCN had a superparamagnetic behavior, which should be contributed by the Fe3O4 core of the MSCN. The saturation magnetization was 6.0 emu/g. When a external magnet was applied, the MSCN could be separated from their dispersion rapidly in less than 3 min, while dispersed again if shaking slightly after withdrawing the magnet (Fig. 3c), indicating a good magnetic response and dispersibility. Because of the excellent drug loading capacity of calcium silicate [14], the as-synthesized MSCN was explored as the drug carrier in this work. Ibuprofen was used as a model drug. The drug loading capacity was measured to be 75 mg drug/g carrier. Fig. 4b shows the ibuprofen drug release profile of the drug loaded MSCN in phosphate buffer saline (PBS) at 37 1C. One can see that the loaded ibuprofen in the MSCN continuously released in a period of 60 h. The release of loaded ibuprofen was rapid in the first 5 h, then gradually slowed down, and the drug release was almost complete at a release time of 60 h. Considering the combined advantages of both sustained drug release and magnetic behavior, the as-synthesized MSCN has the potential application in targeted drug delivery. 4. Conclusions In summary, we have developed a method for synthesizing the hollow-core-double-shell magnetic iron oxide/silica/calcium
silicate nanocomposites. The components of hollow core, middle layer and outer layer are Fe3O4, SiO2, Ca2SiO4, respectively. The hollow core of the MSCN forms at 600 1C within 5 h of heating time by the Oswald ripening process. The poorly crystallized CS layer is formed within 3 h of heating time at 600 1C, and the crystallinity increases with the heating time. The MSCN has a drug loading capacity of 75 mg/g, and the drug can be completely released in a time period of 60 h. The as–prepared MSCN is promising for the potential application in targeted drug delivery.
Acknowledgments This work was supported by the National Basic Research Program of China (973 Program, No. 2012CB933600), the National Natural Science Foundation of China (51172260, 51121064) and the Science and Technology Commission of Shanghai (11nm0506600).
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