Rapid synthesis of hydroxyapatite nanoparticles via a novel approach in the dual-frequency ultrasonic system for specific biomedical application

Abstract

The hydroxyapatite nanoparticles (nHAPs) were synthesized rapidly by the self-assembled dual-frequency ultrasonic method. The ultrasonic time and power effect on the morphology and phase composition of nHAPs were investigated through field-emission scanning electron microscopy (FE-SEM), X-ray diffraction, energy dispersive spectrometer (EDS) spectrometer, and Fourier transform infrared spectroscopy, which showed that the most uniform nanoparticles were obtained when the ultrasonic time was 30 min and the ultrasonic power was 280 W. Cytotoxicity and hemolysis tests showed that an indistinctive cytotoxic effect was within the concentration of 25–400 μg/mL and the hemolytic ratio was below 2.0% at concentration of 25–200 μg/mL, respectively, revealing a good biocompatibility of nHAPs. By loading tetracycline hydrochloride onto nHAPs spheres, the drug release results showed that the drug loading and encapsulation efficiency were (26.34 ± 2.99)% and (52.68 ± 5.98)%, respectively. The drug-loaded sample shows a slow-release property, indicating that nHAPs may be promising as drug carriers.

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References

  1. 1.

    R.B. Martin: Bone as a ceramic composite material. Bioceramics 293, 5–15 (1999).

    CAS  Google Scholar 

  2. 2.

    N. Eliaz, T.M. Sridhar, U. Kamachi Mudali, and B. Raj: Electrochemical and electrophoretic deposition of hydroxyapatite for orthopaedic applications. Surf. Eng. 21, 238–242 (2005). https://doi.org/10.1179/174329405X50091

    CAS  Article  Google Scholar 

  3. 3.

    Z. Yi, K. Wang, J. Tian, Y. Shu, J. Yang, W. Xiao, B. Li, and X. Liao: Hierarchical porous hydroxyapatite fibers with a hollow structure as drug delivery carriers. Ceram. Int. 42, 19079–19085 (2016). https://doi.org/10.1016/j.ceramint.2016.09.067

    CAS  Article  Google Scholar 

  4. 4.

    E.H. Abdulkareem, K. Memarzadeh, R.P. Allaker, J. Huang, J. Pratten, and D. Spratt: Anti-biofilm activity of zinc oxide and hydroxyapatite nanoparticles as dental implant coating materials. J. Dent. 43, 1462–1469 (2015). https://doi.org/10.1016/j.jdent.2015.10.010

    CAS  Article  Google Scholar 

  5. 5.

    Z. Zhang, C. Yan, D. Jin, X. Jia, J. Zhou, and H. Lv: Solid dispersion of berberine–phospholipid complex/TPGS 1000/SiO2: Preparation, characterization and in vivo studies. Int. J. Pharm. 465, 306–316 (2014).

    CAS  Article  Google Scholar 

  6. 6.

    W. Tang, Y. Yuan, C. Liu, Y. Wu, X. Lu, and J. Qian: Differential cytotoxicity and particle action of hydroxyapatite nanoparticles in human cancer cells. Nanomedicine 9, 397–412 (2013). https://doi.org/10.2217/nnm.12.217

    Article  CAS  Google Scholar 

  7. 7.

    S.K. Ghosh, S.K. Nandi, B. Kundu, S. Datta, D.K. De, S.K. Roy, and D. Basu: In vivo response of porous hydroxyapatite and beta-tricalcium phosphate prepared by aqueous solution combustion method and comparison with bioglass scaffolds. J. Biomed. Mater. Res., Part B 86, 217 (2008).

    Article  CAS  Google Scholar 

  8. 8.

    Q.Y. Xiao, K.C. Zhou, C. Chen, M.X. Jiang, Y. Zhang, H. Luo, and D. Zhang: Hollow and porous hydroxyapatite microspheres prepared with an O/W emulsion by spray freezing method. Mater. Sci. Eng., C 69, 1068–1074 (2016). https://doi.org/10.1016/j.msec.2016.07.082

    CAS  Article  Google Scholar 

  9. 9.

    B.A.E. Ben-Arfa, I.M.M. Salvado, J.M.F. Ferreira, and R.C. Pullar: Novel route for rapid sol–gel synthesis of hydroxyapatite, avoiding ageing and using fast drying with a 50-fold to 200-fold reduction in process time. Mater. Sci. Eng., C 70, 796–804 (2017).

    CAS  Article  Google Scholar 

  10. 10.

    M.C. Wang, M.H. Hon, H.T. Chen, F.L. Yen, I.M. Hung, H.H. Ko, and W.J. Shih: Process parameters on the crystallization and morphology of hydroxyapatite powders prepared by a hydrolysis method. Metall. Mater. Trans. A 44, 3344–3352 (2013).

    CAS  Article  Google Scholar 

  11. 11.

    B. Jokic, M. Mitric, V. Radmilovic, S. Drmanic, R. Petrovic, and D. Janackovic: Synthesis and characterization of monetite and hydroxyapatite whiskers obtained by a hydrothermal method. Ceram. Int. 37, 167–173 (2011). https://doi.org/10.1016/j.ceramint.2010.08.032

    CAS  Article  Google Scholar 

  12. 12.

    S. Mondal, R. Bardhan, B. Mondal, A. Dey, S.S. Mukhopadhyay, S. Roy, R. Guha, and K. Roy: Synthesis, characterization and in vitro cytotoxicity assessment of hydroxyapatite from different bioresources for tissue engineering application. Bull. Mater. Sci. 35, 683–691 (2012).

    CAS  Article  Google Scholar 

  13. 13.

    H.X. Xu, B.W. Zeiger, and K.S. Suslick: Sonochemical synthesis of nanomaterials. Chem. Soc. Rev. 42, 2555–2567 (2013).

    CAS  Article  Google Scholar 

  14. 14.

    C. Qi, Y.J. Zhu, C.T. Wu, T.W. Sun, Y.Y. Jiang, Y.G. Zhang, J. Wu, and F. Chen: Sonochemical synthesis of hydroxyapatite nanoflowers using creatine phosphate disodium salt as an organic phosphorus source and their application in protein adsorption. RSC Adv. 6, 9686–9692 (2016). https://doi.org/10.1039/C5RA26231C

    CAS  Article  Google Scholar 

  15. 15.

    K.H. Wong, G.Q. Li, K.M. Li, V. Razmovskinaumovski, and K. Chan: Optimisation of Pueraria isoflavonoids by response surface methodology using ultrasonic-assisted extraction. Food Chem. 231, 231–237 (2017).

    CAS  Article  Google Scholar 

  16. 16.

    M. Sadat-Shojai, M-T. Khorasani, E. Dinpanah-Khoshdargi, and A. Jamshidi: Synthesis methods for nanosized hydroxyapatite with diverse structures. Acta Biomater. 9, 7591–7621 (2013).

    CAS  Article  Google Scholar 

  17. 17.

    P. Rouhani, N. Taghavinia, and S. Rouhani: Rapid growth of hydroxyapatite nanoparticles using ultrasonic irradiation. Ultrason. Sonochem. 17, 853–856 (2010). https://doi.org/10.1016/j.ultsonch.2010.01.010

    CAS  Article  Google Scholar 

  18. 18.

    M.A. Giardina and M.A. Fanovich: Synthesis of nanocrystalline hydroxyapatite from Ca(OH)2 and H3PO4 assisted by ultrasonic irradiation. Ceram. Int. 36, 1961–1969 (2010).

    CAS  Article  Google Scholar 

  19. 19.

    H-L. Liu and C-M. Hsieh: Single-transducer dual-frequency ultrasound generation to enhance acoustic cavitation. Ultrason. Sonochem. 16, 431–438 (2009).

    CAS  Article  Google Scholar 

  20. 20.

    P.A. Tatake and A.B. Pandit: Modelling and experimental investigation into cavity dynamics and cavitational yield: Influence of dual frequency ultrasound sources. Chem. Eng. Sci. 57, 4987–4995 (2002).

    CAS  Article  Google Scholar 

  21. 21.

    S.T. Deng, H. Yu, D. Liu, and Y.G. Bi: Comparison of morphology and phase composition of hydroxyapatite nanoparticles sonochemically synthesized with dual- or single-frequency ultrasonic reactor. Appl. Phys. A 123, 642 (2017). https://doi.org/10.1007/s00339-017-1243-4

    Article  CAS  Google Scholar 

  22. 22.

    R.H. Zeng, T.Q. Qiu, and H.Q. Lu: Increasing extraction of traditional Chinese medicine with cavitation using dual-frequency ultrasound. Tech. Acoust. 24, 219–222 (2005).

    Google Scholar 

  23. 23.

    X. Zhang: Study on the mechanism and extraction of active ingredients from Pueraria Hoot by dual-frequency ultrasound. Sci. Technol. Food Ind. 23, 23–26 (2006).

    Google Scholar 

  24. 24.

    U. Holzwarth and N. Gibson: The Scherrer equation versus the’ Debye–Scherrer equation’. Nat. Nanotechnol. 6, 534 (2011). https://doi.org/10.1038/nnano.2011.145

    CAS  Article  Google Scholar 

  25. 25.

    M. Kavitha, R. Subramanian, K.S. Vinoth, R. Narayanan, G. Venkatesh, and N. Esakkiraja: Optimization of process parameters for solution combustion synthesis of Strontium substituted Hydroxyapatite nanocrystals using design of experiments approach. Powder Technol. 271 (Feb 2015), 167–181 (2014).

    Google Scholar 

  26. 26.

    A. Jankoviæ, S. Erakoviæ, M. Mitriæ, I.Z. Matiæ, Z.D. Juraniæ, G.C.P. Tsui, C-y. Tang, V. Miškoviæ-Stankoviæ, K.Y. Rhee, and S.J. Park: Bioactive hydroxyapatite/graphene composite coating and its corrosion stability in simulated body fluid. J. Alloys Compd. 624, 148–157 (2015).

    Article  CAS  Google Scholar 

  27. 27.

    F. Castro, S. Kuhn, K. Jensen, A. Ferreira, F. Rocha, A. Vicente, and J.A. Teixeira: Continuous-flow precipitation of hydroxyapatite in ultrasonic microsystems. Chem. Eng. J. 215–216, 979–987 (2013).

    Article  CAS  Google Scholar 

  28. 28.

    M. Sadat-Shojai, M.T. Khorasani, and A. Jamshidi: Hydrothermal processing of hydroxyapatite nanoparticles—A Taguchi experimental design approach. J. Cryst. Growth 361, 73–84 (2012).

    CAS  Article  Google Scholar 

  29. 29.

    M.C. Barbosa, N.R. Messmer, T.R. Brazil, F.R. Marciano, and A.O. Lobo: The effect of ultrasonic irradiation on the crystallinity of nano-hydroxyapatite produced via the wet chemical method. Mater. Sci. Eng., C 33, 2620–2625 (2013). https://doi.org/10.1016/j.msec.2013.02.027

    CAS  Article  Google Scholar 

  30. 30.

    G.E. Poinern, R.K. Brundavanam, N. Mondinos, and Z.T. Jiang: Synthesis and characterisation of nanohydroxyapatite using an ultrasound assisted method. Ultrason. Sonochem. 16, 469–474 (2009).

    CAS  Article  Google Scholar 

  31. 31.

    H. Bensalah, M.F. Bekheet, S.A. Younssi, M. Ouammou, and A. Gurlo: Hydrothermal synthesis of nanocrystalline hydroxyapatite from phosphogypsum waste. J. Environ. Chem. Eng. 6, 1347–1352 (2018).

    CAS  Article  Google Scholar 

  32. 32.

    M. Canillas, R. Rivero, R. García-Carrodeguas, F. Barba, and M.A. Rodríguez: Processing of hydroxyapatite obtained by combustion synthesis. Bol. Soc. Esp. Ceram. Vidrio 56, 47–52 (2017). https://doi.org/10.1016/j.bsecv.2017.05.002

    Article  Google Scholar 

  33. 33.

    K.S. Suslick and G.J. Price: Applications of ultrasound to materials chemistry. Annu. Rev. Mater. Sci. 29, 29–34 (1999). https://doi.org/10.1146/annurev.matsci.29.1.295

    Article  Google Scholar 

  34. 34.

    Y.H. Yang, C.H. Liu, Y.H. Liang, F.H. Lin, and K.C.W. Wu: Hollow mesoporous hydroxyapatite nanoparticles (hmHANPs) with enhanced drug loading and pH-responsive release properties for intracellular drug delivery. J. Mater. Chem. B 1, 2447–2450 (2013).

    CAS  Article  Google Scholar 

  35. 35.

    F. Bakan, O. Lacin, and H. Sarac: A novel low temperature sol–gel synthesis process for thermally stable nano crystalline hydroxyapatite. Powder Technol. 233, 295–302 (2013).

    CAS  Article  Google Scholar 

  36. 36.

    W.P.S.L. Wijesinghe, M.M.M.G.P.G. Mantilaka, R.M.G. Rajapakse, H.M.T.G.A. Pitawala, T.N. Premachandra, H.M.T.U. Herath, R.P.V.J. Rajapakse, and K.G.U. Wijayantha: Urea-assisted synthesis of hydroxyapatite nanorods from naturally occurring impure apatite rocks for biomedical applications. RSC Adv. 7, 24806–24812 (2017).

    CAS  Article  Google Scholar 

  37. 37.

    Y.Q. Chen, X.F. Xing, and W.M. Gao: Synthesis of spherical nano-hydroxyapatite by hydrothermal method with L-lysine template. Key Eng. Mater. 633, 17–20 (2014).

    Article  CAS  Google Scholar 

  38. 38.

    S. Utara and J. Klinkaewnarong: Sonochemical synthesis of nano-hydroxyapatite using natural rubber latex as a templating agent. Ceram. Int. 41 (10, Part B), 14860–14867 (2015).

    CAS  Article  Google Scholar 

  39. 39.

    J. Sun, X. Zheng, L. Hui, D. Fan, Z. Song, H. Ma, X. Hua, and J. Hui: Monodisperse selenium-substituted hydroxyapatite: Controllable synthesis and biocompatibility. Mater. Sci. Eng., C 73, 596 (2017).

    CAS  Article  Google Scholar 

  40. 40.

    Y. Sun, X. Wu, L. Chen, and L. Luo: Synthesis and cytotoxicity of N,N′-dibisphosphonate ethylenediamine derivatives and platinum(II) complexes with high binding property to hydroxyapatite. Inorg. Chim. Acta 457, 225–243 (2016).

    Google Scholar 

  41. 41.

    R. Palanivelu and K.A. Ruban: Synthesis, characterization, in vitro anti-proliferative and hemolytic activity of hydroxyapatite. Spectrochim. Acta, Part A 127, 434 (2014).

    CAS  Article  Google Scholar 

  42. 42.

    K.P. Tank, K.S. Chudasama, V.S. Thaker, and M.J. Joshi: Pure and zinc doped nano-hydroxyapatite: Synthesis, characterization, antimicrobial and hemolytic studies. J. Cryst. Growth 401, 474–479 (2014).

    CAS  Article  Google Scholar 

  43. 43.

    V. Uskokoviæ and T.A. Desai: Phase composition control of calcium phosphate nanoparticles for tunable drug delivery kinetics and treatment of osteomyelitis. II. Antibacterial and osteoblastic response. J. Biomed. Mater. Res., Part A 101, 1416–1426 (2013).

    Article  CAS  Google Scholar 

  44. 44.

    J. Qin, Z. Zhong, and J. Ma: Biomimetic synthesis of hybrid hydroxyapatite nanoparticles using nanogel template for controlled release of bovine serum albumin. Mater. Sci. Eng., C 62, 377 (2016).

    CAS  Article  Google Scholar 

  45. 45.

    W. Lai, C. Chen, X. Ren, I.S. Lee, G. Jiang, and X. Kong: Hydrothermal fabrication of porous hollow hydroxyapatite microspheres for a drug delivery system. Mater. Sci. Eng., C 62, 166–172 (2016).

    CAS  Article  Google Scholar 

  46. 46.

    S.C. Thomas, H. Sharma, P. Rawat, A.K. Verma, A. Leekha, V. Kumar, A. Tyagi, B.S. Gurjar, Z. Iqbal, and S. Talegaonkar: Synergistic anticancer efficacy of bendamustine hydrochloride loaded bioactive hydroxyapatite nanoparticles: In vitro, ex vivo and in vivo evaluation. Colloids Surf., B 146, 852–860 (2016).

    CAS  Article  Google Scholar 

  47. 47.

    J.S. Cho, J.C. Lee, and S.H. Rhee: Effect of precursor concentration and spray pyrolysis temperature upon hydroxyapatite particle size and density. J. Biomed. Mater. Res., Part B 104, 422 (2016).

    CAS  Article  Google Scholar 

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Acknowledgments

This work was supported by the Open Project Program of The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, South China University of Technology, Guangzhou Higher Education Mega Centre, Guangzhou 510006, PR China (No. 201701), Research and Demonstration on the Key Technology of Drinking Water and Sewage Treatment in the Northwest Desertification Area (No. 2016YFC0400707), Guangdong Provincial Department of Water Resources Project (No. 2015-20), and Guangdong Provincial Archives Project (No. YDK-141-2016).

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Correspondence to Yong-guang Bi.

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Deng, St., Lin, Zt., Tang, Hx. et al. Rapid synthesis of hydroxyapatite nanoparticles via a novel approach in the dual-frequency ultrasonic system for specific biomedical application. Journal of Materials Research 34, 2796–2806 (2019). https://doi.org/10.1557/jmr.2019.119

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