Materials Letters 91 (2013) 35–38
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Synthesis of calcium phosphate ﬂuoride hybrid hollow spheres Jingxian Zhang n, Dongliang Jiang, Zhongming Chen, Zhengren Huang State Key Laboratory of High Performance Ceramics and Superﬁne Microstructure, Shanghai Institute of Ceramics, Shanghai 200050, China
a r t i c l e i n f o
Article history: Received 15 May 2012 Accepted 15 September 2012 Available online 25 September 2012
We demonstrate the synthesis of calcium phophate ﬂuoride hybrid hollow spheres with well controlled size and morphology through self assembly process using Poly (ethylene oxide)–poly (propylene oxide)–poly (ethylene oxide) triblock copolymer (Pluronic P123) as the template. The diameter and the shell thickness of the hollow spheres is typically in the range of 100–600 nm and 150–200 nm respectively. Scanning electron microscope (SEM), Energy dispersive X-ray spectrometer (EDX), Transmission electron microscopy (TEM) and N2 adsorption–desorption analyses conﬁrmed that well organized hollow spherical structures have been developed. The formation mechanism is attributed to the change in the hydrophobic–hydrophilic balance by the ﬂuoride ions (F ). Our result provides a simple route for the synthesis of inorganic hollow spheres by templating strategies. & 2012 Elsevier B.V. All rights reserved.
Keywords: Biomaterials Nanoparticles
1. Introduction Synthesis of inorganic materials with hollow spherical structure has received a great deal of attention in recent years due to their wide variety of applications, which include the delivery and controlled release of drugs, dyes or inks; as catalysts and catalyst supports; as photonic materials; encapsulation and protection of biological macromolecules; and ﬁllers for composites . There have been a number of methods for the preparation of inorganic materials with hollow spherical structures, such as nozzle-reaction system, emulsion/phase separation, emulsion/ interfacial polymerization, and self-assembly processes. The most effective method is via a self-assembly process, which is also known as the core–shell technique. The assembly of shell materials onto the core template results in composite materials containing a core–shell structure. The removal of the template by calcinations or exposure to an appropriate solvent yields the desired hollow structures. Hollow spheres, including glass, ceramics, semiconductors, magnetic materials and biomaterials, have been synthesized using ‘‘hard templates’’, such as silica spheres , mesoporous carbon  and core–shell gel particles ; and ‘‘soft templates’’, such as vesicles , liquid droplets, and emulsion droplets . Calcium phosphate, which is chemically similar to bones and hard tissues found in humans, is bioactive and can be rapidly integrated into the human body. Therefore, the usage of calcium phosphate hollow sphere has been proposed as a promising technology for biological applications including drug or nutrient-delivering,
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biocompatible and bioresorbable structural reinforcements etc . However, calcium phosphate is not stable in acid atmosphere, such as in stomach. On the contrary, calcium ﬂuoride is relatively more stable. Fluoride is a naturally occurring compound found in water, plants, rocks, soil, air and most foods, such as tea and yolk of eggs. In the ﬁeld of medicine, ﬂuorine is a component of a wide range of modern drugs including anti-cancer and anti-viral agents, antiinﬂammatory drugs, antibiotics, central nervous system agents, and antiarrhythmic heart drugs . It was reported that CaF2 can dissolve slowly in vivo and form a stable bioactive phase (ﬂuorapatite) with HPO4 2 . Li reported that long-term exposure to ﬂuoride in the drinking water, even at an elevated level, does not have genotoxic effects in humans . Therefore, the Ca–F–P–O hybrid hollow sphere might be an attractive candidate for biological application. However, because of the technical difﬁculties, there is no report in literature about Ca–F–P–O hybrid hollow spheres . Herein we report a simple route to synthesize hybrid hollow Ca–P–F–O spheres by conventional route similar to the preparation of SBA-15 using P123 as the template. The microstructure and the relevant forming mechanism were studied.
2. Experimental procedure Poly (ethylene oxide)–poly (propylene oxide)–poly (ethylene oxide) (PEO–PPO–PEO) triblock copolymer (Pluronic P123), calcium nitrate tetrahydrate (Ca(NO3)2 4H2O, Sinopharm chemical reagent Co. Ltd), disodium glycerophosphate, and hydroﬂuoric acid (HF, Sinopharm chemical reagent Co. Ltd) were used as the starting materials. All chemicals were used without further puriﬁcation.
J. Zhang et al. / Materials Letters 91 (2013) 35–38
In a typical procedure, 4.0 g of P123 was dissolved in 120 g of 0.25 M HCl solution with stirring. Then 0.8 g of HF and 2.88 g of disodium glycerophosphate were added with stirring for 12 h at 35 1C using water bath. Subsequently, 3.33 g of Ca(NO3)2 4H2O was dissolved in 20 g of H2O (5 mmol) and the obtained solution was added dropwise to the above solution with stirring at 35 1C. After aging, the resulting precipitation was ﬁltered, washed with de-ionized water and ethanol and then dried at 100 1C for 24 h. Calcinations of this hybrid calcium phosphate was carried out at 400 1C for 1–12 h in air. Powder XRD patterns were obtained on a D/MAX 2250 V diffractometer (Rigaku, Japan) using CuKa radiation (l¼1.5406 F). Morphologies and microstructures of the products were investigated by TEM (JEM-2100F) and ﬁeld emission SEM (JSM-6700F). N2 adsorption– desorption isotherms were obtained using an ASAP 2010 volumetric adsorption analyzer (Micromeritics, Norcross, GA, USA) at 77 K. Brunauer, Emmett, and Teller (BET) and Barrett, Joyner, and Halenda (BJH) analyses were used to determine the surface area, pore size, and pore volume.
The size of the Ca–F–P–O hollow spheres was estimated to be about 100–1000 nm, most frequently in the 100–600 nm range, (Supplementary Fig. 1). The thickness of the shell is in the range of 30–220 nm, most frequently in the 150–200 nm range. The EDS spectrum shows that the hollow sphere is composed of Ca, P, F and O, with a chemical composition of 34:4:46:15 (Supplementary Fig. 2). The as-prepared products were characterized by X-ray diffraction, (Fig. 2). The reﬂection peaks could be indexed to be CaF2.
Ca 5F(PO4) 3
after calcination before calcination
3. Results and discussions A high-resolution transmission electron microscope (HRTEM) was used to characterize the synthesized hollow spheres. Fig. 1a and b showed two HRTEM images of uniform and regular hollow spherical particles. When the sample was continuously tilted, the light contrast in the central part did not vary in contrast and size. This excludes the possibility of solid spheres and suggests the hollow nature of the synthesized Ca–P–F–O particles. The HRTEM of a single hollow sphere exhibits the clear mesoporous structure on the spherical surface and the hollow center, (Fig. 1b). This hollow spherical structure is also conﬁrmed by SEM micrographs, (Fig. 1c and d).
2θ Fig. 2. XRD proﬁles of Ca–F–P–O hybrid hollow spheres before and after calcinations at 400 1C.
Fig. 1. Micrographs of hybrid Ca–F–P–O hollow spheres. TEM (a) (b); SEM (c) (d).
J. Zhang et al. / Materials Letters 91 (2013) 35–38
Calcium phosphate might be in amorphorous phase. After calcinations, the CaF2 phase was still in existence and the new peaks cannot be indexed to be any phase, but is more close the peak for Ca5(PO4)3 F (JCPDS: 34-0011). N2 adsorption–desorption isotherms and pore size distributions of mesoporous calcium phosphate after calcinations are shown in Fig. 3. The well deﬁned hysteresis loop between the adsorption and desorption branches can be classiﬁed as type H3 according to the IUPAC classiﬁcation , indicative of slitshaped pores. One noticeable characteristic was its unusually large pore size. This sample possessed narrow pore size distributions with the peak pore diameters at 20.70 nm. The pore volume (Vp) and the speciﬁc surface areas were 0.41 cm3/g and 89.58 m2/g respectively. The pore volume is comparable to those for mesoporous silica, is expected to ﬁnd applications as delivery vehicles in the pharmaceutical and cosmetic industries. The low speciﬁc surface area might be due to the collapsed porous structure after calcinations. The products obtained could be controlled by carefully adjusting the synthesis temperature and composition. The suitable temperature is around 35 1C, an increase or decrease will lead to the formation of incomplete hollow spheres. The concentration of HF is less than
300 250 200 150 100 50 0
0.7 M, too high will lead to the formation of platelike CaF2 particles. The HCl content can be kept in the 0.2–0.3 M range. At high HCl content (0.43 M), however, hollow blocks other than hollow spheres were observed, (Supplementary Fig. 3a and b). The addition of ethanol did not show obvious effect on the size and microstructure of the hollow spheres. The mechanism of the formation of Ca–F–P–O hollow sphere is probably attributed to the change in the hydrophobic–hydrophilic balance by the ﬂuoride ions (F ). Block copolymers consisting of polyethylene oxide (PEO) and polypropylene oxide (PPO) exhibit amphiphilic character and can self-assemble in the aqueous solution . Basically, the driving force for the phase evolution of the surfactant assemblies (e.g., the shape and size of the micelle) is closely related to the hydrophobic–hydrophilic balance or the packing parameters of surfactant in the emulsion . As F is cosmotropic ions, we can anticipate that it will compete for water with the ether groups of PEO segments, leading to dehydration of the surface . The removal of water from the PEO hydration shell, probably can tune the interfacial energy and effective area per headgroup and thus the hydrophilic–lipophilic balance as well as packing parameters (v/(al)). Therefore, it is proposed that the presence of F might shift the hydrophobic– hydrophilic equilibrium of the P123–NaF–H3O þ emulsion system from the hexagonal to laminar region, similar to the inﬂuence of temperature on the phase behavior of alkane-P123–TEOS–NH4F– H3O þ system . At this stage, the packing parameters might stay at the boundary of two mesophases (i.e., H1 and LR). The addition of disodium glycerophosphate could presumably help the layered structure to close and form hollow spheres. A continuous shearing force (in the present case, mechanical stirring) was involved during the synthesis, which is reported to be also able to drive those lamellar structures into vesicles . After the addition of Ca(NO3)2 4H2O, the Ca–P–F–O shells might be developed outside the hollow spheres and ﬁnally the spherical particles were formed (Fig. 4).
P/P0 Fig. 3. N2 adsorption–desorption isotherms of Ca–F–P–O hybrid hollow spheres after calcinations at 400 1C.
We have developed a facile route to synthesize hybrid Ca–F– P–O hollow spheres with the assistance of P123. Typically, the diameter and the shell thickness of the synthesized hollow spheres is in the range of 100–600 nm and 150–200 nm respectively. These hierarchical hollow spheres may ﬁnd applications in
Fig. 4. Schematic illustration of the pore forming mechanism.
J. Zhang et al. / Materials Letters 91 (2013) 35–38
a wide range of areas such as delivery vehicle systems, ﬁllers, catalysts and waste removal.
Acknowledgement This work was supported by the National Natural Science Foundation of China (No. 50990301, 51072210), Shanghai Science and Technology Committee and the State Key Laboratory of High Performance Ceramics and Superﬁne Microstructures.
Appendix A. Supporting information Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/j.matlet.2012.09.048.
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