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Mesoporous silica SBA-16/hydroxyapatite-based composite for ciprofloxacin delivery to bacterial bone infection

  • Original Paper: Sol-gel and hybrid materials for biological and health (medical) applications
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Abstract

The development of systems that can prevent infections and also ensure bone integration as well as regeneration have been of great interest for pharmaceutical technology. In this study, we show the synthesis of surface-functionalized mesoporous silica (SBA-16) and silica composed of calcium phosphate (SBA-16/HA) particles in order to be applied as efficient drug delivery carriers. The particles were synthesized, functionalized with 3-aminopropyltriethoxysilane (APTES) by post-synthesis grafting and loaded with the osteomyelitis antibiotic agent ciprofloxacin. Moreover, the diethylenetriaminepentacetic acid (DTPA) was anchored in silica-APTES to allow measurements of biological process at molecular and cellular levels. Particles were physicochemically characterized by small angle X-ray scattering (SAXS), elemental analysis (CHN), thermogravimetric analysis (TGA), N2 adsorption and zeta potential analysis. Functionalized silica particles were radiolabeled with technetium-99m showing high radiochemical yields and high radiolabeled stability. In vivo experiments results showed higher bone uptake of the SBA-16/HAAPTES than SBA-16APTES. In addition, bactericidal efficacy of these particles was tested against microorganisms present in bone infection, and our composites had bactericidal efficiency comparable to free-ciprofloxacin. In summary, taking into account the great potential of these silica mesoporous and nanocomposite structures to carry molecules, besides their bactericidal efficacy, these materials are promising candidates for bone infection treatment.

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References

  1. Arcos D, Vallet-Regí M (2010) Sol-gel silica-based biomaterials and bone tissue regeneration. Acta Biomater 6:2874–2888. https://doi.org/10.1016/j.actbio.2010.02.012

    Article  Google Scholar 

  2. Devanand Venkatasubbu G, Ramasamy S, Ramakrishnan V, Kumar J (2011) Nanocrystalline hydroxyapatite and zinc-doped hydroxyapatite as carrier material for controlled delivery of ciprofloxacin. 3 Biotech 1:173–186. https://doi.org/10.1007/s13205-011-0021-9

    Article  Google Scholar 

  3. Andersson DI, Hughes D (2010) Antibiotic resistance and its cost: is it possible to reverse resistance? Nat Rev Microbiol 8:260–271. https://doi.org/10.1038/nrmicro2319

    Article  Google Scholar 

  4. Capeletti LB, Oliveira LF De, Gonçalves KDA, et al. (2014) Tailored silica-antibiotic nanoparticles: overcoming bacterial resistance with low cytotoxicity. https://doi.org/10.1021/la4046435

  5. Drlica K (1999) Mechanism of fluoroquinolone action. Curr Opin Microbiol 2:504–508. https://doi.org/10.1016/S1369-5274(99)00008-9

    Article  Google Scholar 

  6. Redgrave LS, Sutton SB, Webber MA, Piddock LJ (2014) Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success. Trends Microbiol 22:438–445

    Article  Google Scholar 

  7. Kim HW, Knowles JC, Kim HE (2004) Hydroxyapatite/poly(??-caprolactone) composite coatings on hydroxyapatite porous bone scaffold for drug delivery. Biomaterials 25:1279–1287. https://doi.org/10.1016/j.biomaterials.2003.07.003

    Article  Google Scholar 

  8. Blasi F, Aliberti S, Tarsia P (2007) Clinical applications of azithromycin microspheres in respiratory tract infections. Int J Nanomed 2:551–559

    Google Scholar 

  9. Tang F, Li L, Chen D (2012) Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater 24:1504–1534. https://doi.org/10.1002/adma.201104763

    Article  Google Scholar 

  10. Cassidy JW (2015) Nanotechnology in the regeneration of complex tissues. Bone Tissue Regen Insights 5:25–35. https://doi.org/10.4137/BTRI.S12331.Nanotechnology

    Google Scholar 

  11. Juhasz JA, Best SM (2012) Bioactive ceramics: processing, structures and properties. J Mater Sci 47:610–624. https://doi.org/10.1007/s10853-011-6063-x

    Article  Google Scholar 

  12. Wu C, Chang J (2012) Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application. Interface Focus 2:292–306. https://doi.org/10.1098/rsfs.2011.0121

    Article  Google Scholar 

  13. Valente FL, Reis ECC, Sepúlveda RV et al. (2016) Hydroxyapatite, polycaprolactone and alendronate composites for bone regeneration in rabbits’ olecranon: histological features. Arq Bras Med Vet e Zootec 68:543–547. https://doi.org/10.1590/1678-4162-8343

    Article  Google Scholar 

  14. Dasgupta S, Banerjee SS, Bandyopadhyay A, Bose S (2010) Zn- and Mg-doped hydroxyapatite nanoparticles for controlled release of protein. Langmuir 26:4958–4964. https://doi.org/10.1021/la903617e

    Article  Google Scholar 

  15. Andrade GF, Gomide VS, da Silva Júnior AC et al. (2014) An in situ synthesis of mesoporous SBA-16/hydroxyapatite for ciprofloxacin release: in vitro stability and cytocompatibility studies. J Mater Sci Mater Med 25:2527–2540. https://doi.org/10.1007/s10856-014-5273-6

    Article  Google Scholar 

  16. Andrade GF, Carvalho JL, Júnior ASC et al. (2015) Osteogenic differentiation of adipose-derived stem cells in mesoporous SBA-16 and SBA-16 hydroxyapatite scaffolds. RSC Adv 5:54551–54562. https://doi.org/10.1039/C5RA07330H

    Article  Google Scholar 

  17. Gobin OC (2006) SBA-16 materials synthesis, diffusion and sorption properties. Laval University, Ste-Foy, Quebec, Canada

  18. Díaz A, López T, Manjarrez J et al. (2006) Growth of hydroxyapatite in a biocompatible mesoporous ordered silica. Acta Biomater 2:173–179. https://doi.org/10.1016/j.actbio.2005.12.006

    Article  Google Scholar 

  19. Izquierdo-Barba I, Sousa E, Doadrio JC et al. (2009) Influence of mesoporous structure type on the controlled delivery of drugs: Release of ibuprofen from MCM-48, SBA-15 and functionalized SBA-15. J Sol-Gel Sci Technol 50:421–429. https://doi.org/10.1007/s10971-009-1932-3

    Article  Google Scholar 

  20. Andrade GF, Soares DCF, dos Santos RG, Sousa EMB (2013) Mesoporous silica SBA-16 nanoparticles: synthesis, physicochemical characterization, release profile, and in vitro cytocompatibility studies. Microporous Mesoporous Mater 168:102–110. https://doi.org/10.1016/j.micromeso.2012.09.034

    Article  Google Scholar 

  21. de Barros ALB, de Oliveira Ferraz KS, Dantas TCS et al. (2015) Synthesis, characterization, and biodistribution studies of 99mTc-labeled SBA-16 mesoporous silica nanoparticles. Mater Sci Eng C 56:181–188. https://doi.org/10.1016/j.msec.2015.06.030

    Article  Google Scholar 

  22. Ehlert N, Badar M, Christel A et al. (2011) Mesoporous silica coatings for controlled release of the antibiotic ciprofloxacin from implants. J Mater Chem 21:752. https://doi.org/10.1039/c0jm01487g

    Article  Google Scholar 

  23. Cueva C, Moreno-Arribas MV, Martín-Álvarez PJ et al. (2010) Antimicrobial activity of phenolic acids against commensal, probiotic and pathogenic bacteria. Res Microbiol 161:372–382. https://doi.org/10.1016/j.resmic.2010.04.006

    Article  Google Scholar 

  24. Beck JS, Vartuli JC, Roth WJ, et al. (1992) A new family of mesoporous molecular sieves prepared with liquid crystal templates. J Am Chem Soc 10834. https://doi.org/10.1021/ja00053a020

  25. Costa JAS, Garcia ACFS, Santos DO et al. (2014) A new functionalized MCM-41 mesoporous material for use in environmental applications. J Braz Chem Soc 25:197–207. https://doi.org/10.5935/0103-5053.20130284

    Google Scholar 

  26. Pang J, Zhao L, Zhang L et al. (2013) Folate-conjugated hybrid SBA-15 particles for targeted anticancer drug delivery. J Colloid Interface Sci 395:31–39. https://doi.org/10.1016/j.jcis.2012.12.016

    Article  Google Scholar 

  27. Mouriño V, Boccaccini AR (2010) Bone tissue engineering therapeutics: controlled drug delivery in three-dimensional scaffolds. J R Soc Interface 7:209–227. https://doi.org/10.1098/rsif.2009.0379

    Article  Google Scholar 

  28. Gao P, Nie X, Zou M et al. (2011) Recent advances in materials for extended-release antibiotic delivery system. J Antibiot64:625–634. https://doi.org/10.1038/ja.2011.58

    Article  Google Scholar 

  29. Moritz M, Geszke-Moritz M (2015) Mesoporous materials as multifunctional tools in biosciences: principles and applications. Mater Sci Eng C Mater Biol Appl 49:114–151. https://doi.org/10.1016/j.msec.2014.12.079

    Article  Google Scholar 

  30. Babić S, Horvat AJM, Mutavdžić Pavlović D, Kaštelan-Macan M (2007) Determination of pKa values of active pharmaceutical ingredients. TrAC Trends Anal Chem 26:1043–1061. https://doi.org/10.1016/j.trac.2007.09.004

    Article  Google Scholar 

  31. Berridge MV, Herst PM, Tan AS (2005) Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction. Biotechnol Annu Rev 11:127–152. https://doi.org/10.1016/S1387-2656(05)11004-7

    Article  Google Scholar 

  32. Bancos S, Tsai D-H, Hackley V et al. (2012) Evaluation of viability and proliferation profiles on macrophages treated with silica nanoparticles in vitro via plate-based, flow cytometry, and coulter counter assays. ISRN Nanotechnol 2012:1–11. https://doi.org/10.5402/2012/454072

    Article  Google Scholar 

  33. Pereira VV, Silva RR, Duarte LP, Takahashi JA (2016) Chemical constituents of Jacaranda oxyphylla and their acetylcholinesterase inhibitory and antimicrobial activities. Rec Nat Prod 10:392–396

    Google Scholar 

  34. de Barros ALB, Mota L das G, Ferreira C de A, Cardoso VN (2012) Kit formulation for 99mTc-labeling of HYNIC-ΒAla-Bombesin (7–14). Appl Radiat Isot 70:2440–2445. https://doi.org/10.1016/j.apradiso.2012.06.022

    Article  Google Scholar 

  35. Shin SJ, Beech JR, Kelly KA (2012) Targeted nanoparticles in imaging: paving the way for personalized medicine in the battle against cancer. Integr Biol 5:29–42. https://doi.org/10.1039/c2ib20047c

    Article  Google Scholar 

  36. James H, Thrall HAZ (2003) Medicina Nuclear. In: G Koogan (ed) 2a edn. p. 408. ISBN 852770790X

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Acknowledgements

This work was supported by funding from CAPES, CNPq, and FAPEMIG. Experiments and analyses involving electron microscopy were performed in the Microscopy Center of the Federal University of Minas Gerais, Belo Horizonte, Brazil (http://www.microscopia.ufmg.br). The authors thank the LNLS (Campinas, Brazil) for Synchrotron radiation measurements.

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Authors and Affiliations

  1. Center of Development of the Nuclear Technology, CDTN/CNEN, Belo Horizonte, Brazil

    Gracielle Ferreira Andrade & Edésia Martins Barros de Sousa

  2. Faculty of Pharmacy, Federal University of Minas Gerais—UFMG, Belo Horizonte, Brazil

    Gracielle Ferreira Andrade, André Luís Branco de Barros, Renata Salgado Fernandes & Armando da Silva Cunha Jr

  3. Institute of Biological Science—Departament of Physiological Sciences, Federal University of Amazonas—UFAM, Manaus, Brazil

    Jerusa Araújo Quintão Arantes Faria

  4. Institute of Biological Science—Departament of Biochemistry and Immunology, Federal University of Minas Gerais—UFMG, Belo Horizonte, Brazil

    Dawidson Assis Gomes

  5. Institute of Exact Sciences—Departament of Chemistry, Federal University of Minas Gerais—UFMG, Belo Horizonte, Brazil

    Amanda Cristina Soares Coelho & Jacqueline Aparecida Takahashi

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  1. Gracielle Ferreira Andrade
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Correspondence to Edésia Martins Barros de Sousa.

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Andrade, G.F., Faria, J.A.Q.A., Gomes, D.A. et al. Mesoporous silica SBA-16/hydroxyapatite-based composite for ciprofloxacin delivery to bacterial bone infection. J Sol-Gel Sci Technol 85, 369–381 (2018). https://doi.org/10.1007/s10971-017-4557-y

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  • DOI: https://doi.org/10.1007/s10971-017-4557-y

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