Materials Letters 65 (2011) 2361–2363

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Materials Letters

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Microwave-assisted synthesis of hydroxyapatite hollow microspheres inaqueous solution

Ke-Wei Wang, Ying-Jie Zhu ⁎, Feng Chen, Guo-Feng Cheng, Yue-Hong HuangState Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China

⁎ Corresponding author. Tel.: +86 21 52412616; fax:E-mail address: y.j.zhu@mail.sic.ac.cn (Y.-J. Zhu).

0167-577X/$ – see front matter © 2011 Elsevier B.V. Adoi:10.1016/j.matlet.2011.04.104

a b s t r a c t

a r t i c l e i n f o

Article history:Received 5 March 2011Accepted 28 April 2011Available online 5 May 2011

Keywords:Nanocrystalline materialsNanoparticlesHydroxyapatiteHollow microsphereNanosheetMicrowave

We report a template-free microwave-assisted hydrothermal method for the preparation of hydroxyapatitehollowmicrospheres constructed by the self-assembly of nanosheets using Ca(CH3COO)2, Na2HPO4, NaH2PO4

and sodium citrate in aqueous solution. X-ray powder diffraction (XRD) patterns indicated that the as-prepared samples consisted of hydroxyapatite. Transmission electron microscopy (TEM) and scanningelectron microscopy (SEM) micrographs showed that the as-prepared products were composed of hollowmicrospheres assembled with nanosheets and had three-dimensional nanoporous nanostructured networks.The experimental parameters were varied to investigate their effects on the product, and a possible formationmechanism was proposed. The as-prepared hydroxyapatite hollowmicrospheres have a potential applicationin drug delivery.

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1. Introduction

Materials with hollow structures are of great interest because oftheir unique properties and potential applications in various fieldssuch as drug delivery, energy storage, catalysis, sensors [1–6]. Due tothe biocompatibility and chemical similarity to bone, calciumphosphate (CaP) based materials are considered as excellentcandidates for biomedical applications. The fabrication of CaP hollownanostructures are of both scientific and technological importance.Recently, considerable efforts have been devoted to the preparation ofCaPhollowmicro-/nano-spheres. The templatemethodwas adopted forthe preparation of CaP hollow nanostructures, which was extensivelyused for the synthesis of hollow spheres [7–12]. Meanwhile, template-free approaches, such as polyelectrolyte-mediated mineralization andpolyaspartate controlled synthesis [13,14], hydrothermal method [15],and ultrasonic technique [16]were also explored to prepare CaP hollownanostructures. Although some progress has been made, it is stilldesirable to developnew fabrication routes to CaPhollowmicrospheres.

In this paper, we report a microwave-assisted hydrothermalmethod for the preparation of hydroxyapatite (HAp) hollow micro-spheres constructed by the self-assembly of nanosheets. The reagentsused in this study are common and inexpensive. The effects ofexperimental parameters on the product are also investigated anddiscussed. This method is facile and rapid, and the as-prepared HAphollow microspheres are promising for application in biomedicalareas such as drug delivery.

2. Experimental section

All chemicals were purchased from Sinopharm Chemical ReagentCo. and used as received without further purification. In a typicalexperiment, 0.059 g of sodium citrate dihydrate (Na3Cit·2H2O) and10 mL of aqueous solution containing Na2HPO4 (0.04 M) and NaH2PO4

(0.04 M) was added into 20 mL of deionized water, and the pH valueof the above solution was adjusted to 5.0 by using 0.5 M HCl. Then10 mL of Ca(CH3COO)2 aqueous solution (0.08 M) was addeddropwise to the phosphate solution to form a clear solution. Thefinal concentrations of the resulting solution were Na2HPO4 (10 mM),NaH2PO4 (10 mM), Ca(CH3COO)2 (20 mM), and Na3Cit (5 mM). Theresulting solution was transferred to a Teflon autoclave (70 mL),sealed, and heated to 120 °C, and kept at this temperature for 30 minusing a microwave-hydrothermal synthesis system (MDS-6, Sineo,Shanghai, China). The product was collected by centrifugation,washed with deionized water and absolute ethanol, and dried invacuum at 40 °C for 24 h.

X-ray powder diffraction (XRD) patterns were recorded on aRigaku D/MAX 2550V X-ray diffractometer using Cu-Kα radiation(λ=1.54178 Å) with a graphite monochromator. The transmissionelectron microscopy (TEM) micrographs were taken with a JEOL JEM-2100 field emission transmission electron microscope. The scanningelectron microscopy (SEM) micrographs were recorded on a JEOLJSM-6700F field emission scanning electron microscope.

3. Results and discussion

The morphologies of the samples were characterized by SEM. Asshown in Fig. 1, microspheres with diameters ranging from 0.5 to

Fig. 1. SEMmicrographs of the samples prepared by microwave-assisted hydrothermal method using Ca(CH3COO)2, Na2HPO4, NaH2PO4 and sodium citrate in aqueous solution. Themicrowave heating time was 30 min for all three samples. (a) and (b) [Na3Cit]=5 mM, 120 °C; (c) and (d) [Na3Cit]=5 mM, 140 °C; (e) and (f) [Na3Cit]=10 mM, 140 °C.

Fig. 2. TEMmicrographs of the samples prepared bymicrowave-assisted hydrothermalmethod. Themicrowave heating timewas 30 min for all three samples. (a) and (b) [Na3Cit]=5mM,120 °C; (c) and (d) [Na3Cit]=5mM, 140 °C; (e) and (f) [Na3Cit]=10mM, 140 °C.

Fig. 3. XRD patterns of the samples prepared by microwave-assisted hydrothermalmethod. For all three samples: [Na3Cit]=5 mM, microwave heating time=30 min.(a) 80 °C; (b) 120 °C; and (c) 140 °C.

2362 K.-W. Wang et al. / Materials Letters 65 (2011) 2361–2363

2 μm were obtained by the microwave-assisted hydrothermal methodusing Ca(CH3COO)2, Na2HPO4, NaH2PO4 and sodium citrate in aqueoussolution. From the magnified SEM images (Fig. 1b, d and f), one can seethat these microspheres were constructed by the self-assembly of alarge number of nanosheets, the thicknesses of the nanosheets as thebuilding blocks were less than 50 nm. The effects of the reactiontemperature and Na3Cit concentration on the morphology of thesamples were also investigated. Compared to the sample prepared at120 °C (Fig. 1a and b), themicrospheres synthesized at 140 °C exhibitedamore compactmorphology (Fig. 1c and d).Moreover, when theNa3Citconcentration increased from 5 mM (Fig. 1c and d) to 10 mM (Fig. 1eand f), the sizes of the nanosheets as the building blocks decreased.

Fig. 2 shows TEMmicrographs of the samples, from which one cansee that the interior of the microspheres was hollow with ananoporous three-dimensional network, which is advantageous fordrug loading and sustained release.

Fig. 4. TEMmicrographs of the samples prepared by microwave-assisted hydrothermal method. The microwave heating time was 30min for all three samples. (a) and (b) [Na3Cit]=0mM,120 °C; (c) and (d) [Na3Cit]=2.5 mM, 140 °C; (e) and (f) [Na3Cit]=5mM, 80 °C.

2363K.-W. Wang et al. / Materials Letters 65 (2011) 2361–2363

The crystal phase of the samples was characterized by XRD. Fig. 3shows XRD patterns of the samples prepared by microwave-assistedhydrothermal method at 80, 120 and 140 °C, respectively. The crystalphase of the samples can be indexed to hydroxyapatite (HAp) with ahexagonal structure (JCPDS 09-0432).

To further investigate the effect of Na3Cit on the product, parallelexperiments with and without Na3Cit were carried out. As shown inFig. 3a and b, only dispersed nanosheets instead of microspheres wereobtained in the absence of Na3Cit, indicating the important role ofNa3Cit in the formation of hollow microspheres constructed by theself-assembly of nanosheets. The sample obtained using 2.5 mMNa3Cit also consisted of hollow microspheres constructed by the self-assembly of nanosheets (Fig. 4c and d), but the hollow interior wasnot as obvious as that of the sample prepared using 5 mM Na3Cit(Fig. 2c and d), and the sizes of nanosheets as the building blocks alsoincreased. Interestingly, the sample synthesized at 80 °C for 30 minalso consisted of hydroxyapatite hollowmicrospheres assembledwithnanosheets, indicating the hydroxyapatite hollow microspheres canbe fabricated at a relatively low temperature.

Based on the above experimental results, we propose an assem-bling–repelling mechanism to elucidate the formation of hydroxyapa-tite hollow microspheres constructed by the self-assembly ofnanosheets. During the microwave-hydrothermal process, HApnanosheets are firstly formed, and these HAp nanosheets are boundtogether towards micro-aggregates through the interaction between –

COO groups of Na3Cit molecules and Ca2+ ions of the HAp nanosheets,thus an assembling process occurs. In the meantime, the electrostaticrepelling force also exists between neighboring nanosheets, and hencehollowmicrospheres assembledwith nanosheets are formed due to thedelicate balance between the assembling effect and repelling force.

4. Conclusions

In summary, we have demonstrated amicrowave-assisted hydrother-mal method for the preparation of hydroxyapatite hollow microspheresformed by the self-assembly of nanosheets using Ca(CH3COO)2, Na2HPO4,

NaH2PO4 and sodium citrate in aqueous solution. The hydroxyapatitehollowmicrosphereshavediameters ranging from0.5 to2 μmandexhibitthree-dimensional nanoporous network structure. The use of inexpensivereagents, relatively low and flexible temperature (80–140 °C) and shortreaction time (30 min) make this approach rapid and economical. Ascalcium phosphate nanostructured materials are receiving more andmore attention in the biomedical fields, the as-prepared hydroxyapatitehollowmicrospheres are promising for the application in drug delivery asdrug nanocarriers.

Acknowledgments

The authors are grateful for the financial support from the Scienceand Technology Commission of Shanghai (1052nm06200), theNational Natural Science Foundation of China (50821004) and theState Key Laboratory of High Performance Ceramics and SuperfineMicrostructure.

References

[1] Wang YJ, Yan Y, Cui JW, Hosta-Rigau L, Heath JK, Nice EC, et al. AdvMater 2010;22:4293–7.

[2] Tan LF, Chen D, Liu HY, Tang FQ. Adv Mater 2010;22:4885–9.[3] Huo J, Wang L, Irran E, Yu HJ, Gao JM, Fan DS, et al. Angew Chem Int Ed Engl

2010;49:9237–41.[4] Li GL, Shi Q, Yuan SJ, Neoh KG, Kang ET, Yang XL. Chem Mater 2010;22:1309–17.[5] Zhu J, Tang JW, Zhao LZ, Zhou XF, Wang YH, Yu CZ. Small 2010;6:276–82.[6] Cao CY, Cui ZM, Chen CQ, Song WG, Cai W. J Phys Chem C 2010;114:9865–70.[7] Ma MY, Zhu YJ, Li L, Cao SW. J Mater Chem 2008;18:2722–7.[8] Tjandra W, Ravi P, Yao J, Tam KC. Nanotechnology 2006;17:5988–94.[9] Ye F, Guo HF, Zhang HJ, He XL. Acta Biomater 2010;6:2212–8.[10] Wang YS, Moo YX, Chen CP, Gunawan P, Xu R. J Colloid Interface Sci 2010;352:

393–400.[11] Shanthi PMSL, Mangalaraja RV, Uthirakumar AP, Velmathi S, Balasubramanian T,

Ashok M. J Colloid Interface Sci 2010;350:39–43.[12] Schmidt HT, Ostafin AE. Adv Mater 2002;14:532–5.[13] Bigi A, Boanini E, Walsh D, Mann S. Angew Chem Int Ed Engl 2002;41:2163–6.[14] Peytcheva A, Colfen H, Schnablegger H, Antonietti M. Colloid Polym Sci 2002;280:

218–27.[15] Kandori K, Noguchi Y, Fukusumi M, Morisada Y. J Phys Chem C 2010;114:6440–5.[16] Cai YR, Pan HH, Xu XR, Hu QH, Li L, Tang RK. Chem Mater 2007;19:3081–3.