Nanostructured hollow spheres of hydroxyapatite: preparation and potential application in drug delivery

Abstract

A solvothermal method has been successfully used to prepare nanostructured hydroxyapatite (HA) hollow spheres with average diameters of about 500 nm and shell thicknesses of about 100 nm in a glycerin/water mixed solvent. Transmission electron microscopy (TEM) and field-emission scanning electron microscopy (FESEM) images show that the shells of the HA hollow spheres are actually composed of nanosheets with thicknesses of about 10 nm. By tuning the glycerin/water volume ratio, two other kinds of HA solid spheres with average diameters of about 6 or 20 μm were assembled from nanoflakes. The properties of the different kinds of spheres as drug delivery carriers were evaluated. Ibuprofen (IBU) was chosen as the model drug to load into the HA samples. The nanostructured HA samples showed a slow and sustained release of IBU. The HA hollow spheres exhibited a higher drug loading capacity and more favorable release properties than the HA solid spheres and thus are very promising for controlled drug release applications.

Keywords

hydroxyapatite / hollow spheres / synthesis / drug release

References

[1] Ma M Y, Zhu Y J, Li L, Cao S W. Nanostructured porous hollow ellipsoidal capsules of hydroxyapatite and calcium silicate: preparation and application in drug delivery. Journal of Materials Chemistry, 2008, 18(23): 2722–2727

[2] Uskoković V, Uskoković D P. Nanosized hydroxyapatite and other calcium phosphates: chemistry of formation and application as drug and gene delivery agents. Journal of Biomedical Materials Research Part B: Applied Biomaterials, 2011, 96(1): 152–191

[3] Zhang H G, Zhu Q S, Wang Y. Morphologically controlled synthesis of hydroxyapatite with partial substitution of fluorine. Chemistry of Materials, 2005, 17(23): 5824–5830

[4] Tseng Y H, Mou C Y, Chan J C. Solid-state NMR study of the transformation of octacalcium phosphate to hydroxyapatite: a mechanistic model for central dark line formation. Journal of the American Chemical Society, 2006, 128(21): 6909–6918

[5] Cao X Y, Wen F, Bian W, Cao Y, Pang S J, Zhang W K. Preparation and comparison study of hydroxyapatite and Eu-hydroxyapatite. Frontiers of Materials Science in China, 2009, 3(3): 255–258

[6] Jagadeesan D, Deepak C, Siva K, Inamdar M S, Eswaramoorthy M. Carbon Spheres Assisted Synthesis of Porous Bioactive Glass Containing Hydroxycarbonate Apatite Nanocrystals: a Material with High in Vitro Bioactivity. Journal of Physical Chemistry C, 2008, 112(19): 7379–7384

[7] Zhu D M, Wang F, Gao C L, Xu Z. Construction of PS/PNIPAM core-shell particles and hollow spheres by using hydrophobic interaction and thermosensitive phase separation. Frontiers of Chemical Engineering in China, 2008, 2(3): 253–256

[8] Lächelt U, Wagner E. Invading target cells: multifunctional polymer conjugates as therapeutic nucleic acid carriers. Frontiers of Chemical Science and Engineeringβ, 2011, 5(3): 275–286

[9] Almirall A, Larrecq G, Delgado J A, Martínez S, Planell J A, Ginebra M P. Fabrication of low temperature macroporous hydroxyapatite scaffolds by foaming and hydrolysis of an α-TCP paste. Biomaterials, 2004, 25(17): 3671–3680

[10] Ma M G, Zhu J F. Solvothermal synthesis and characterization of hierarchically nanostructured hydroxyapatite hollow spheres. European Journal of Inorganic Chemistry, 2009, 36: 5522–5526

[11] Sun R X, Lu Y P, Chen K Z. Preparation and characterization of hollow hydroxyapatite microspheres by spray drying method. Materials Science and Engineering: C, 2009, 29(4): 1088–1092

[12] Shum H C, Bandyopadhyay A, Bose S, Weitz D A. Double emulsion droplets as microreactors for synthesis of mesoporous. Chemistry of Materials, 2009, 21(22): 5548–5555

[13] Sun R X, Chen K Z, Lu Y P. Fabrication and dissolution behavior of hollow hydroxyapatite microspheres intended for controlled drug release. Materials Research Bulletin, 2009, 44(10): 1939–1942

[14] Cheng X K, He Q J, Li J Q, Huang Z L, Chi R A. Control of pore size of the bubble-template porous carbonated hydroxyapatite microsphere by adjustable pressure. Crystal Growth & Design, 2009, 9(6): 2770–2775

[15] Cheng X K, Huang Z L, Li J Q, Liu Y, Chen C L, Chi R A, Hu Y H. Self-assembled growth and pore size control of the bubble-template porous carbonated hydroxyapatite microsphere. Crystal Growth & Design, 2010, 10(3): 1180–1188

[16] Jiang H Z, Stupp S I. Dip-pen patterning and surface assembly of peptide amphiphiles. Langmuir, 2005, 21(12): 5242–5246

[17] Zhang W X, Yang Z H, Liu Y, Tang S P, Han X Z, Chen M. Controlled synthesis of Mn₃O₄ nanocrystallites and MnOOH nanorods by a solvothermal method. Journal of Crystal Growth, 2004, 263(1-4): 394–399

[18] Steiner Z, Rapaport H, Oren Y, Kasher R. Effect of surface-exposed chemical groups on calcium-phosphate mineralization in water-treatment systems. Environmental Science & Technology, 2010, 44(20): 7937–7943

[19] Yang Z H, Zhao M, Florin N H, Harris A T. Synthesis and characterization of CaO nanopods for high temperature CO₂ capture. Industrial & Engineering Chemistry Research, 2009, 48(24): 10765–10770

[20] Mizushima Y, Ikoma T, Tanaka J, Hoshi K, Ishihara T, Ogawa Y, Ueno A. Injectable porous hydroxyapatite microparticles as a new carrier for protein and lipophilic drugs. Journal of Controlled Release, 2006, 110(2): 260–265

[21] Ito M, Hidaka Y, Nakajima M, Yagasaki H, Kafrawy A H. Effect of hydroxyapatite content on physical properties and connective tissue reactions to a chitosan-hydroxyapatite composite membrane. Journal of Biomedical Materials Research, 1999, 45(3): 204–208

[22] Wang H X, Guan S K, Wang Y S, Liu H J, Wang H T, Wang L G, Ren C X, Zhu S J, Chen K S. In vivo degradation behavior of Ca-deficient hydroxyapatite coated Mg-Zn-Ca alloy for bone implant application. Colloids and Surfaces. B, Biointerfaces, 2011, 88(1): 254–259

[23] Aoki H, Aoki H, Kutsuno T, Li W, Niwa M. An in vivo study on the reaction of hydroxyapatite-sol injected into blood. Journal of Materials Science. Materials in Medicine, 2000, 11(2): 67–72

[24] Zhang C M, Cheng Z Y, Yang P P, Xu Z H, Peng C, Li G G, Lin J. Architectures of strontium hydroxyapatite microspheres: solvothermal synthesis and luminescence properties. Langmuir, 2009, 25(23): 13591–13598

[25] Yao A H, Ai F R, Liu X, Wang D P, Huang W H, Xu W. Preparation of hollow hydroxyapatite microspheres by the conversion of borate glass at near room temperature. Materials Research Bulletin, 2010, 45(1): 25–28

[26] Pon-On W, Meejoo S, Tang I M. Formation of hydroxyapatite crystallites using organic template of polyvinyl alcohol (PVA) and sodium dodecyl sulfate (SDS). Materials Chemistry and Physics, 2008, 112(2): 453–460

[27] Porter A, Patel N, Brooks R, Best S, Rushton N, Bonfield W. Effect of carbonate substitution on the ultrastructural characteristics of hydroxyapatite implants. Journal of Materials Science. Materials in Medicine, 2005, 16(10): 899–907

[28] Wu Y J, Bose S. Nanocrystalline hydroxyapatite: micelle templated synthesis and characterization. Langmuir, 2005, 21(8): 3232–3234

[29] Wang A J, Lu Y P, Zhu R F, Li S T, Xiao G Y, Zhao G F, Xu W H. Effect of sintering on porosity, phase, and surface morphology of spray dried hydroxyapatite microspheres. Journal of Journal of Biomedical MaterialsResearch. Part A, 2008, 87(2): 557–562

Acknowledgments

The authors are grateful to the financial support of the National Natural Science Foundation of China (Grants Nos. 20871038, 20976033 and 21176054), the Fundamental Research Fund for the Central Universities (2010HGZY0012) and the Education Department of Anhui Provincial Government (TD200702).

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg