Biocompatible Glasses for Controlled Release Technology

  • Roger Borges
  • Karen Cristina Kai
  • Juliana MarchiEmail author
Part of the Advanced Structured Materials book series (STRUCTMAT, volume 53)


In order to treat, relief or prevent diseases, new drugs and alternative procedures have been continuously developed. Recently, the introduction of concepts involving controlled release technology brought new perspectives for the development of drug systems. These systems aim to diminish drugs side effects and, at the same time, to increase their efficacy. In this sense, bioactive glasses have been used as new carrier systems to delivery ions, bioactive molecules (including drugs) and even cells. In this chapter, it was covered most of the main characteristics of bioactive glasses that must be take into account during the development of new carrier systems: glass composition, morphology and its interaction with the chosen drug. A relevant discussion about composites consisted of polymer/bioactive glasses was also included along the chapter. Finally, some of the most recent pharmacological breakthroughs using bioactive glasses are reviewed, such as applications in bone regeneration, osteomyelitis and cancer treatment.


Bone Regeneration Bioactive Glass Bioactive Molecule Guide Bone Regeneration Control Release System 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Alberts, B., et al.: General principles of cell communication. In: NCBI Bookshelf. Molecular Biology of the Cell, 4th edn. Garland Science, New York (2002)Google Scholar
  2. 2.
    Wilson, C.G.: The need for drugs and drug delivery systems. In: Siepmann, J., et al. (eds.) Fundamentals and Applications of Controlled Release Drug Delivery. Advances in Delivery Science and Technology, pp. 3–18 (2012). doi: 10.1007/978-1-4614-0881-9_9
  3. 3.
    Arcos, D., Vallet-Regí, M.: Bioceramics for drug delivery. Acta Mater. 61, 890–911 (2013). doi: 10.1016/j.actamat.2012.10.039 CrossRefGoogle Scholar
  4. 4.
    Yun, Y.H., Lee, B.K., Park, K.: Controlled drug delivery: historical perspective for the next generation. J. Controlled Release 219, 2–7 (2015). doi: 10.1016/j.jconrel.2015.10.005 CrossRefGoogle Scholar
  5. 5.
    Mager, D.E.: Quantitative structure–pharmacokinetic/pharmacodynamic relationships. Adv. Drug Deliv. Rev. 58, 1326–1356 (2006). doi: 10.1016/j.addr.2006.08.002 CrossRefGoogle Scholar
  6. 6.
    Gabrielsson, J., Green, A.R.: Quantitative pharmacology or pharmacokinetic pharmacodynamic integration should be a vital component in integrative pharmacology. J. Pharmacol. Exp. Ther. 331, 767–774 (2009). doi: 10.1124/jpet.109.157172 CrossRefGoogle Scholar
  7. 7.
    Asín-Prieto, E., Rodríguez-Gascón, A., Isla, A.: Applications of the pharmacokinetic/pharmacodynamic (PK/PD) analysis of antimicrobial agents. J. Infect. Chemother. 21, 319–329 (2015). doi: 10.1016/j.jiac.2015.02.001 CrossRefGoogle Scholar
  8. 8.
    Acharya, G., Park, K.: Mechanisms of controlled drug release from drug-eluting stents. Adv. Drug Deliv. Rev. 58, 387–401 (2006). doi: 10.1016/j.addr.2006.01.016 CrossRefGoogle Scholar
  9. 9.
    Lee, J.H., Yeo, Y.: Controlled drug release from pharmaceutical nanocarriers. Chem. Eng. Sci. 125, 75–84 (2015). doi: 10.1016/j.ces.2014.08.046 CrossRefGoogle Scholar
  10. 10.
    Hughes, G.A.: Nanostructure-mediated drug delivery. Nanomed. Nanotechnol. Biol. Med. 1, 22–30 (2005). doi: 10.1016/j.nano.2004.11.009 CrossRefGoogle Scholar
  11. 11.
    Tiwari, G., et al.: Drug delivery systems: an updated review. Int. J. Pharm. Investig. 2, 2–11 (2012). doi: 10.4103/2230-973X.96920 CrossRefGoogle Scholar
  12. 12.
    Reddy, L.H., Bazile, D.: Drug delivery design for intravenous route with integrated physicochemistry, pharmacokinetics and pharmacodynamics: illustration with the case of taxane therapeutics. Adv. Drug Deliv. Rev. 71, 34–57 (2014). doi: 10.1016/j.addr.2013.10.007 CrossRefGoogle Scholar
  13. 13.
    Hum, J., Boccaccini, A.R.: Bioactive glasses as carriers for bioactive molecules and therapeutic drugs: a review. J. Mater. Sci. Mater. Med. 23, 2317–2333 (2012). doi: 10.1007/s10856-012-4580-z CrossRefGoogle Scholar
  14. 14.
    Wu, C., Chang, J.: Mesoporous bioactive glasses: structure characteristics, drug/growth factor delivery and bone regeneration application. Interface Focus 2, 292–306 (2012). doi: 10.1098/rsfs.2011.0121 CrossRefGoogle Scholar
  15. 15.
    Park, K.: Facing the truth about nanotechnology in drug delivery. ACS Nano 7, 7442–7447 (2013). doi: 10.1021/nn404501g CrossRefGoogle Scholar
  16. 16.
    Park, K.: Drug delivery of the future: controlled drug delivery systems: past forward and future back. J. Controlled Release 190, 3–8 (2014). doi: 10.1016/j.jconrel.2014.03.054 CrossRefGoogle Scholar
  17. 17.
    Zhang, Y., Chan, H.F., Leong, K.W.: Advanced materials and processing for drug delivery: the past and the future. Adv. Drug Deliv. Rev. 65, 104–120 (2013). doi: 10.1016/j.addr.2012.10.003 CrossRefGoogle Scholar
  18. 18.
    Safari, J., Zarnegar, Z.: Advanced drug delivery systems: nanotechnology of health design: a review. J. Saudi Chem. Soc. 18, 85–99 (2014). doi: 10.1016/j.jscs.2012.12.009 CrossRefGoogle Scholar
  19. 19.
    Park, K.: Drug delivery of the future: chasing the invisible gorilla. J. Controlled Release (2015). doi: 10.1016/j.jconrel.2015.10.048 Google Scholar
  20. 20.
    Xia, Y., Pack, D.W.: Uniform biodegradable microparticle systems for controlled release. Chem. Eng. Sci. 125, 129–143 (2015). doi: 10.1016/j.ces.2014.06.049 CrossRefGoogle Scholar
  21. 21.
    Torchilin, V.: Multifunctional and stimuli-sensitive pharmaceutical nanocarriers. Eur. J. Pharm. Biopharm. 71, 431–444 (2009). doi: 10.1016/j.ejpb.2008.09.026 CrossRefGoogle Scholar
  22. 22.
    Sarkhel, S., et al.: High-throughput in vitro drug release and pharmacokinetic simulation as a tool for drug delivery system development: application to intravitreal ocular administration. Int. J. Pharm. 477, 469–475 (2014). doi: 10.1016/j.ijpharm.2014.10.062 CrossRefGoogle Scholar
  23. 23.
    Tongwen, X., Binglin, H.: Mechanism of sustained drug release in diffusion-controlled polymer matrix-application of percolation theory. Int. J. Pharm. 170, 139–149 (1998). doi: 10.1016/S0378-5173(97)00402-X CrossRefGoogle Scholar
  24. 24.
    Siepmann, J., Siepmann, S.: Mathematical modeling of drug delivery. Int. J. Pharm. 364, 328–343 (2008). doi: 10.1016/j.ijpharm.2008.09.004 CrossRefGoogle Scholar
  25. 25.
    Fu, Y., Kao, W.J.: Drug release kinetics and transport mechanisms of nondegradable and degradable polymeric delivery systems. Expert Opin. Drug Deliv. 7, 429–444 (2010). doi: 10.1517/17425241003602259 CrossRefGoogle Scholar
  26. 26.
    Raval, A., Parikh, J., Engineer, C.: Mechanism of controlled release kinetics from medical devices. Braz. J. Chem. Eng. 27, 211–225 (2010). doi: 10.1590/S0104-66322010000200001 Google Scholar
  27. 27.
    Mönkäre, J., et al.: Characterization of internal structure, polymer erosion and drug release mechanisms of biodegradable poly(ester anhydride)s by X-ray microtomography. Eur. J. Pharm. Sci. 47, 170–178 (2012). doi: 10.1016/j.ejps.2012.05.013 CrossRefGoogle Scholar
  28. 28.
    Cheng, W., Gu, L., Ren, W., Liu, Y.: Stimuli-responsive polymers for anti-cancer drug delivery. Mater. Sci. Eng. C 45, 600–608 (2014). doi: 10.1016/j.msec.2014.05.050 CrossRefGoogle Scholar
  29. 29.
    Kaim, W., Schwederski, B., Klein, A.: Bioinorganic chemisitry—inorganic elements in the chemistry of life: an introduction and guide. In: Kaim, W., Schwederski, B., Klein, A. (eds.), 1st edn. John Wiley and Sons, Chichester (2013). ISBN: 9780470975237Google Scholar
  30. 30.
    Hoppe, A., Mourino, V., Boccaccini, A.R.: Therapeutic inorganic ions in bioactive glasses to enhance bone formation and beyond. Biomater. Sci. 1, 254–256 (2013). doi: 10.1039/c2bm00116k CrossRefGoogle Scholar
  31. 31.
    Zanotto, E.D., Coutinho, F.A.B.: How many non-crystalline solids can be made from all the elements of the periodic table? J. Non Cryst. Solids 347, 285–288 (2004). doi: 10.1016/j.jnoncrysol.2004.07.081 CrossRefGoogle Scholar
  32. 32.
    Shruti, S., Salinas, A.J., Ferrari, E., et al.: Curcumin release from cerium, gallium and zinc containing mesoporous bioactive glasses. Microporous Mesoporous Mater. 180, 92–101 (2013). doi: 10.1016/j.micromeso.2013.06.014 CrossRefGoogle Scholar
  33. 33.
    El-Kady, A.M., Ali, A.F., Rizk, R.A., Ahmed, M.M.: Synthesis, characterization and microbiological response of silver doped bioactive glass nanoparticles. Ceram. Int. 38, 177–188 (2012). doi: 10.1016/j.ceramint.2011.05.158 CrossRefGoogle Scholar
  34. 34.
    Wu, C., Chang, J.: Multifunctional mesoporous bioactive glasses for effective delivery of therapeutic ions and drug/growth factors. J. Control Release 193, 1–14 (2014). doi: 10.1016/j.jconrel.2014.04.026 CrossRefGoogle Scholar
  35. 35.
    Xia, W., Chang, J.: Well-ordered mesoporous bioactive glasses (MBG): a promising bioactive drug delivery system. J. Control Release 110, 522–530 (2006). doi: 10.1016/j.jconrel.2005.11.002 CrossRefGoogle Scholar
  36. 36.
    Zhu, Y., Zhu, M., He, X., et al.: Substitutions of strontium in mesoporous calcium silicate and their physicochemical and biological properties. Acta Biomater. 9, 6723–6731 (2013). doi: 10.1016/j.actbio.2013.01.021 CrossRefGoogle Scholar
  37. 37.
    Ye, J., He, J., Wang, C., et al.: Copper-containing mesoporous bioactive glass coatings on orbital implants for improving drug delivery capacity and antibacterial activity. Biotechnol. Lett. 36, 961–968 (2014). doi: 10.1007/s10529-014-1465-x CrossRefGoogle Scholar
  38. 38.
    Rahaman, M.N., Bal, B.S., Huang, W.: Review: emerging developments in the use of bioactive glasses for treating infected prosthetic joints. Mater. Sci. Eng. C 41, 224–231 (2014). doi: 10.1016/j.msec.2014.04.055 CrossRefGoogle Scholar
  39. 39.
    Kouhi, M., Morshed, M., Varshosaz, J., Fathi, M.H.: Poly (ε-caprolactone) incorporated bioactive glass nanoparticles and simvastatin nanocomposite nanofibers: preparation, characterization and in vitro drug release for bone regeneration applications. Chem. Eng. J. 228, 1057–1065 (2013). doi: 10.1016/j.cej.2013.05.091 CrossRefGoogle Scholar
  40. 40.
    Manzano, M., Vallet-Regi, M.: Revising bioceramics: bone regenerative and local drug delivery systems. Prog. Solid State Chem. 40, 17–30 (2012). doi: 10.1016/j.progsolidstchem.2012.05.001 CrossRefGoogle Scholar
  41. 41.
    Provenzano, M.J., Murphy, K.P.J., Riley, L.H.: Bone cements: review of their physiochemical and biochemical properties in percutaneous vertebroplasty. Am. J. Neuroradiol. 25, 1286–1290 (2004)Google Scholar
  42. 42.
    Olalde, B., Garmendia, N., Sáez-Martínez, V., et al.: Multifunctional bioactive glass scaffolds coated with layers of poly(d, l-lactide-co-glycolide) and poly(n-isopropylacrylamide-co-acrylic acid) microgels loaded with vancomycin. Mater. Sci. Eng. C 33, 3760–3767 (2013). doi: 10.1016/j.msec.2013.05.002 CrossRefGoogle Scholar
  43. 43.
    Li, W., Ding, Y., Rai, R., et al.: Preparation and characterization of PHBV microsphere/45S5 bioactive glass composite scaffolds with vancomycin releasing function. Mater. Sci. Eng. C 41, 320–328 (2014). doi: 10.1016/j.msec.2014.04.052 CrossRefGoogle Scholar
  44. 44.
    Li, W., Nooeaid, P., Roether, J.A., et al.: Preparation and characterization of vancomycin releasing PHBV coated 45S5 Bioglass??-based glass-ceramic scaffolds for bone tissue engineering. J. Eur. Ceram. Soc. 34, 505–514 (2014). doi: 10.1016/j.jeurceramsoc.2013.08.032 CrossRefGoogle Scholar
  45. 45.
    Cui, X., Gu, Y., Li, L., et al.: In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites. J. Mater. Sci. Mater. Med. 24, 2391–2403 (2013). doi: 10.1007/s10856-013-4996-0 CrossRefGoogle Scholar
  46. 46.
    Ding, H., Zhao, C.J., Cui, X., et al.: A novel injectable borate bioactive glass cement as an antibiotic delivery vehicle for treating osteomyelitis. PLoS ONE 9, 1–9 (2014). doi: 10.1371/journal.pone.0085472 CrossRefGoogle Scholar
  47. 47.
    Hong, K.S., Kim, E.C., Bang, S.H., et al.: Bone regeneration by bioactive hybrid membrane containing FGF2 within rat calvarium. J. Biomed. Mater. Res., Part A 94, 1187–1194 (2010). doi: 10.1002/jbm.a.32799 Google Scholar
  48. 48.
    Rivadeneira, J., et al.: Novel antibacterial bioactive glass nanocomposite functionalized wuth tetracycline hydrochloride. Biomed. Glasses 1, 128–135 (2015). doi: 10.1515/bglass-2015-0012 CrossRefGoogle Scholar
  49. 49.
    Patel, K.D., El-Fiqi, A., Lee, H.-Y., et al.: Chitosan–nanobioactive glass electrophoretic coatings with bone regenerative and drug delivering potential. J. Mater. Chem. 22, 24945–24956 (2012). doi: 10.1039/c2jm33830k CrossRefGoogle Scholar
  50. 50.
    Ordikhani, F., Simchi, A.: Long-term antibiotic delivery by chitosan-based composite coatings with bone regenerative potential. Appl. Surf. Sci. 317, 56–66 (2014). doi: 10.1016/j.apsusc.2014.07.197 CrossRefGoogle Scholar
  51. 51.
    Pishbin, F., Mouriño, V., Flor, S., et al.: Electrophoretic deposition of gentamicin-loaded bioactive glass/chitosan composite coatings for orthopaedic implants. ACS Appl. Mater. Interfaces 6, 8796–8806 (2014). doi: 10.1021/am5014166 CrossRefGoogle Scholar
  52. 52.
    Kresge, C.T., Leonowicz, M.E., Roth, W.J., et al.: Ordered mesoporous molecular sieves synthesized by a liquid-crystal template mechanism. Nature 359, 710–712 (1992)CrossRefGoogle Scholar
  53. 53.
    Yan, X., Yu, C., Zhou, X., et al.: Highly ordered mesoporous bioactive glasses with superior in vitro bone-forming bioactivities. Angew. Chem. Int. Ed. 43, 5980–5984 (2004). doi: 10.1002/anie.200460598 CrossRefGoogle Scholar
  54. 54.
    Yan, X., Huang, X., Yu, C., et al.: The in-vitro bioactivity of mesoporous bioactive glasses. Biomaterials 27, 3396–3403 (2006). doi: 10.1016/j.biomaterials.2006.01.043 CrossRefGoogle Scholar
  55. 55.
    Haro Durand, L.A., Góngora, A., Porto López, J.M., et al.: In vitro endothelial cell response to ionic dissolution products from boron-doped bioactive glass in the SiO2–CaO–P2O5–Na2O system. J. Mater. Chem. B 2, 7620–7630 (2014). doi: 10.1039/C4TB01043D CrossRefGoogle Scholar
  56. 56.
    Hoppe, A., Güldal, N.S., Boccaccini, A.R.: Biomaterials A review of the biological response to ionic dissolution products from bioactive glasses and glass-ceramics. Biomaterials 32, 2757–2774 (2011). doi: 10.1016/j.biomaterials.2011.01.004 CrossRefGoogle Scholar
  57. 57.
    Zhang, Y., Wei, L., Chang, J., et al.: Strontium-incorporated mesoporous bioactive glass scaffolds stimulating in vitro proliferation and differentiation of bone marrow stromal cells and in vivo regeneration of osteoporotic bone defects. J. Mater. Chem. B 1, 5711 (2013). doi: 10.1039/c3tb21047b CrossRefGoogle Scholar
  58. 58.
    Mendes, L.S., Saska, S., Martines, M.A.U., Marchetto, R.: Nanostructured materials based on mesoporous silica and mesoporous silica/apatite as osteogenic growth peptide carriers. Mater. Sci. Eng. C Mater. Biol. Appl. 33, 4427–4434 (2013). doi: 10.1016/j.msec.2013.06.040 CrossRefGoogle Scholar
  59. 59.
    Li, X., Chen, X., Miao, G., et al.: Synthesis of radial mesoporous bioactive glass particles to deliver osteoactivin gene. J. Mater. Chem. B 2, 7045–7054 (2014). doi: 10.1039/C4TB00883A CrossRefGoogle Scholar
  60. 60.
    Wu, C., Fan, W., Chang, J., Xiao, Y.: Mesoporous bioactive glass scaffolds for efficient delivery of vascular endothelial growth factor. J. Biomater. Appl. 28, 367–374 (2013). doi: 10.1177/0885328212453635 CrossRefGoogle Scholar
  61. 61.
    Wu, C., Zhou, Y., Chang, J., Xiao, Y.: Delivery of dimethyloxallyl glycine in mesoporous bioactive glass scaffolds to improve angiogenesis and osteogenesis of human bone marrow stromal cells. Acta Biomater. 9, 9159–9168 (2013). doi: 10.1016/j.actbio.2013.06.026 CrossRefGoogle Scholar
  62. 62.
    Perez, R., El-Fiqi, A., Park, J.-H., et al.: Therapeutic bioactive microcarriers: co-delivery of growth factors and stem cells for bone tissue engineering. Acta Biomater. 10, 520–530 (2014). doi: 10.1016/j.actbio.2013.09.042 CrossRefGoogle Scholar
  63. 63.
    Zeng, Q., Han, Y., Li, H., Chang, J.: Bioglass/alginate composite hydrogel beads as cell carriers for bone regeneration. J. Biomed. Mater. Res. Part B Appl. Biomater. 102, 42–51 (2014). doi: 10.1002/jbm.b.32978 CrossRefGoogle Scholar
  64. 64.
    Wu, C., Fan, W., Chang, J.: Functional mesoporous bioactive glass nanospheres: synthesis, high loading efficiency, controllable delivery of doxorubicin and inhibitory effect on bone cancer cells. J. Mater. Chem. B 1, 2710 (2013). doi: 10.1039/c3tb20275e CrossRefGoogle Scholar
  65. 65.
    Zhang, J., Zhao, S., Zhu, M., et al.: 3D-printed magnetic Fe 3 O 4/MBG/PCL composite scaffolds with multifunctionality of bone regeneration, local anticancer drug delivery and hyperthermia. J. Mater. Chem. B 2, 7583–7595 (2014). doi: 10.1039/C4TB01063A CrossRefGoogle Scholar
  66. 66.
    Lin, H.-M., Lin, H.-Y., Chan, M.-H.: Preparation, characterization, and in vitro evaluation of folate-modified mesoporous bioactive glass for targeted anticancer drug carriers. J. Mater. Chem. B 1, 6147 (2013). doi: 10.1039/c3tb20867b CrossRefGoogle Scholar
  67. 67.
    Mouriño, V., Newby, P., Pishbin, F., et al.: Physicochemical, biological and drug-release properties of gallium crosslinked alginate/nanoparticulate bioactive glass composite films. Soft Matter 7, 6705 (2011). doi: 10.1039/c1sm05331k CrossRefGoogle Scholar
  68. 68.
    Chengtie, Wu, Chang, Jiang, Fan, Wei: Bioactive mesoporous calcium-silicate nanoparticles with excellent mineralization ability, osteostimulation, drug-delivery and antibacterial properties for filling apex roots of teeth. J. Mater. Chem. 22, 16801–16809 (2012). doi: 10.1039/c2jm33387b CrossRefGoogle Scholar
  69. 69.
    Miola, M., Vitale-Brovarone, C., Mattu, C., Verné, E.: Antibiotic loading on bioactive glasses and glass-ceramics: an approach to surface modification. J. Biomater. Appl. 28, 308–319 (2013). doi: 10.1177/0885328212447665 CrossRefGoogle Scholar
  70. 70.
    Ehlert, N., Badar, M., Christel, A., et al.: Mesoporous silica coatings for controlled release of the antibiotic ciprofloxacin from implants. J. Mater. Chem. 21, 752 (2011). doi: 10.1039/c0jm01487g CrossRefGoogle Scholar
  71. 71.
    Mabrouk, M., Mostafa, A.A., Oudadesse, H., et al.: Effect of ciprofloxacin incorporation in PVA and PVA bioactive glass composite scaffolds. Ceram. Int. 40, 4833–4845 (2014). doi: 10.1016/j.ceramint.2013.09.033 CrossRefGoogle Scholar
  72. 72.
    Liu, X., Xie, Z., Zhang, C., et al.: Bioactive borate glass scaffolds: in vitro and in vivo evaluation for use as a drug delivery system in the treatment of bone infection. J. Mater. Sci. Mater. Med. 21, 575–582 (2010). doi: 10.1007/s10856-009-3897-8 CrossRefGoogle Scholar
  73. 73.
    Jia, W.T., Zhang, X., Luo, S.H., et al.: Novel borate glass/chitosan composite as a delivery vehicle for teicoplanin in the treatment of chronic osteomyelitis. Acta Biomater. 6, 812–819 (2010). doi: 10.1016/j.actbio.2009.09.011 CrossRefGoogle Scholar
  74. 74.
    Zhang, X., Jia, W., Gu, Y., et al.: Teicoplanin-loaded borate bioactive glass implants for treating chronic bone infection in a rabbit tibia osteomyelitis model. Biomaterials 31, 5865–5874 (2010). doi: 10.1016/j.biomaterials.2010.04.005 CrossRefGoogle Scholar
  75. 75.
    Xie, Z., Cui, X., Zhao, C., et al.: Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model. Antimicrob. Agents Chemother. 57, 3293–3298 (2013). doi: 10.1128/AAC.00284-13 CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Roger Borges
    • 1
  • Karen Cristina Kai
    • 1
  • Juliana Marchi
    • 1
    Email author
  1. 1.Center for Natural Science and Humanities (CCNH)Federal University of ABC (UFABC)Santo AndréBrazil

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