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Study of a luminescent and antibacterial biomaterial based on hydroxyapatite as support for an antineoplastic drug

Published online by Cambridge University Press:  07 May 2019

Amanda Alves Barbosa*
Affiliation:
Department of Materials Science, Federal University of Pernambuco, Recife, PE 50740-560, Brazil; and Department of Materials Science, Federal University of San Francisco Valley, Juazeiro, BA 48902-300, Brazil
Severino Alves Júnior
Affiliation:
Department of Materials Science, Federal University of Pernambuco, Recife, PE 50740-560, Brazil
Andréa de Vasconcelos Ferraz
Affiliation:
Department of Materials Science, Federal University of San Francisco Valley, Juazeiro, BA 48902-300, Brazil
*
a)Address all correspondence to this author. e-mail: amanda.barbosa@univasf.edu.br
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Abstract

In this work, a multifunctional system was developed in which antibacterial and luminescent properties were inserted into the matrix of hydroxyapatite (HAp) and its efficiency as a support for an antineoplastic drug was evaluated, aiming its application in the treatment of osseous diseases. The precipitation method was used for the synthesis of HAp, EuCl3 was used for the incorporation of Eu3+ as imaging agents, silver nanoparticles (AgNPs) with antimicrobial function were used, and a model of drug, 5-fluorouracil (5FU) was used. The developed material is characterized by several techniques, where crystalline peaks attributed to HAp were identified in the X-ray diffractogram, whereas the luminescence spectrum of the material presented emissions attributed to the Eu3+ ion. The identification and the uniform distribution of AgNPs, 5FU, and Eu3+ were confirmed by mapping the sample using energy-dispersive spectroscopy. The measurements indicated that 82% (±2.8) of 5FU was incorporated into the HAp matrix, and a gradual and increasing release of it as a function of time was observed. Assays carried out for different bacteria confirmed the antimicrobial action of the samples and the efficiency of the drug inserted into the matrix. An in vitro assay showed the bioactivity of the material and its potential to bind to living osseous tissue.

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Article
Copyright
Copyright © Materials Research Society 2019 

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References

Ouyang, L., He, D., Zhang, J., He, G., Jiang, B., Wang, Q., Chen, Z., Pan, J., Li, Y., and Guo, L.: Selective bone targeting 5-fluorouracil prodrugs: Synthesis and preliminary biological evaluation. Bioorg. Med. Chem. 19, 37503756 (2011).CrossRefGoogle ScholarPubMed
Buijs, J.T. and Pluijm, G.V.: Osteotropic cancers: From primary tumor to bone. Cancer Lett. 273, 177193 (2009).CrossRefGoogle ScholarPubMed
Hirabayashi, H. and Fujisaki, J.: Bone-specific drug delivery systems approaches via chemical modification of bone-seeking agents. Clin. Pharmacokinet. 42, 13191330 (2003).CrossRefGoogle ScholarPubMed
Cawthray, J., Wasan, E., and Wasan, K.: Bone-seeking agents for the treatment of bone disorders. Drug Delivery Transl. Res. 7, 466481 (2017).CrossRefGoogle ScholarPubMed
Andronescu, E., Ficai, M., Voicu, G., Ficai, D., Maganu, M., and Ficai, A.: Synthesis and characterization of collagen/hydroxyapatite: Magnetite composite material for bone cancer treatment. J. Mater. Sci.: Mater. Med. 21, 22372242 (2010).Google ScholarPubMed
Marques, C., Ferreira, J.M.F., Adronescu, E., Ficai, D., Sonmez, M., and Ficai, A.: Multifunctional materials for bone cancer treatment. Int. J. Nanomed. 9, 27132725 (2014).Google ScholarPubMed
Kuehl, R., Brunetto, P.S., Woischnig, A.K., Varisco, M., Rajacic, Z., Vosbeck, , Terracciano, L., Fromm, K.M., and Khanna, N.: Preventing implant-associated infections by silver coating. Antimicrob. Agents Chemother. 60, 24672475 (2016).CrossRefGoogle ScholarPubMed
Costa, A.M. and Silva, V.V.: Nanotechnology strategies for diagnosis and treatment of cancer. R. Saúde Meio Amb. 5, 113 (2017).Google Scholar
Liu, Y., Miyoshi, H., and Nakamura, M.: Nanomedicine for drug delivery and imaging: A promising avenue for cancer therapy and diagnosis using targeted functional nanoparticles. Int. J. Cancer 120, 25272537 (2007).CrossRefGoogle ScholarPubMed
Lopes, J.R., Oliveira, J.A., and Esteves, A.A.: Synthesis and characterization of hydroxyapatite powders [Ca10(PO4)6(OH)2] obtained from the sol–gel process. Foco 6, 5572 (2015).Google Scholar
Lin, K. and Chang, J.: Structure and properties of hydroxyapatite for biomedical applications. Hydroxyapatite Biomed. Appl., 319 (2015). doi: 10.1016/B978-1-78242-033-0.00001-8.CrossRefGoogle Scholar
Ashokan, A., Menon, D., Nair, S., and Koyakutty, M.: A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent. Biomaterials 31, 26062616 (2010).CrossRefGoogle ScholarPubMed
Chen, F., Huang, P., Zhu, Y.J., Wu, J., Zhang, C.L., and Cui, D.X.: The photoluminescence, drug delivery and imaging properties of multifunctional Eu3+/Gd3+ dual-doped hydroxyapatite nanorods. Biomaterials 32, 90319039 (2011).CrossRefGoogle ScholarPubMed
de Oliveira, S.V., Cavalcanti, S.N., Rabelo, G.P., Araújo, E.M., and Fook, M.V.L.: Hydroxyapatite infrared analysis. In VI Congr. Nac. Eng. Mec. (Conem), Campina Grande, PB, 2010.Google Scholar
Tseng, C.L., Chen, J.C., Fang, Y.C., Lin, F.H., and Tang, T.P.: Development of lattice-inserted 5-fluorouracil-hydroxyapatite nanoparticles as a chemotherapeutic delivery system. J. Biomater. Appl. 30, 388397 (2015).CrossRefGoogle ScholarPubMed
Singh, P., Tyagi, G., Mehrotra, R., and Bakhshi, A.: Thermal stability studies of 5-fluorouracil using diffuse reflectance infrared spectroscopy. Drug Test. Anal. 1, 240244 (2009).CrossRefGoogle ScholarPubMed
Sing, K.S.W., Everett, D.H., Haul, R.A.W., Moscou, L., Pirotti, R.A., and Rouquerol, J.: Reporting physisorption data for gas/solid systems in. Pure Appl. Chem. 57, 603619 (1985).CrossRefGoogle Scholar
Jin, Y., Wang, A., Wu, G., Yin, H., Liu, S., Chen, B., Liu, F., and Li, X.: Synthesis of different sized and porous hydroxyapatite nanorods without organic modifiers and their 5-fluorouracil release performance. Mater. Sci. Eng., C 57, 1423 (2015).Google Scholar
Martin, P., Carlot, G., Chevarier, A., Den-Auwer, C., and Panczer, G.: Mechanisms involved in thermal diffusion of rare earth elements in apatite. J. Nucl. Mater. 275, 268276 (1999).CrossRefGoogle Scholar
Zavala-Sanchez, L.A., Hirata, G.A., Novitskaya, E., Karandikar, K., Herrera, M., and Graeve, O.A.: Distribution of Eu2+ and Eu3+ ions in hydroxyapatite: A cathodoluminescence and Raman study. ACS Biomater. Sci. Eng. 1, 13061313 (2015).CrossRefGoogle Scholar
Graeve, O.A., Kanakala, R., Madadi, A., Williams, B.C., and Glass, K.C.: Luminescence variations in hydroxyapatites doped with Eu2+ and Eu3+ ions. Biomaterials 31, 42594267 (2010).CrossRefGoogle ScholarPubMed
ANVISA: Standardization of Antimicrobial Susceptibility Tests by Disk-Diffusion: Standard Approved, Octave ed. (2003); p. 23, ISBN 1-56238-485-6.Google Scholar
Nair, K.L., Jagadeeshan, S., Nair, S.A., and Kumar, G.S.: Biological evaluation of 5-fluorouracil nanoparticles for cancer chemotherapy and its dependence on the carrier. PLGA. Int. J. Nanomedic. 6, 16851697 (2011).Google Scholar
Luo, H., Ji, D., Li, C., Zhu, Y., Xiong, G., and Wan, Y.: Layered nanohydroxyapatite as a novel nanocarrier for controlled delivery of 5-fluorouracil. Int. J. Pharm. 513, 1725 (2016).CrossRefGoogle ScholarPubMed
Hardman, J.G., Limbird, L.E., and Gilman, A.G.: Goodman & Gilman's the Pharmacological Basis of Therapeutics, 10th ed. (McGraw-Hill, New York, 2001). Available at: https://pt.wikipedia.org/wiki/Especial:Fontes_de_livros/0071354697. ISBN 0-07-135469-7.Google Scholar
Solomon, S.D., Bahadory, M., Jeyarajasigam, A.V., Rutkowsky, S.A., and Boritz, C.: Synthesis and study of silver nanoparticles. J. Chem. Educ. 84, 322325 (2007).Google Scholar
Kokubo, T. and Takadama, H.: How useful is SBF in predicting in vivo bone bioactivity? Biomaterials 27, 29072915 (2006).CrossRefGoogle ScholarPubMed