Skip to main content
SpringerLink
Log in

Flow Behavior and Drug Release Study of Injectable Pluronic F-127 Hydrogels containing Bioactive Glass and Carbon-Based Nanopowders

  • Published:
Journal of Inorganic and Organometallic Polymers and Materials Aims and scope Submit manuscript

Abstract

Injectable biomaterials have gained significant attention in recent years since they can be delivered to the defect sites through minimally-invasive approaches. In this work, thermo-responsive injectable hydrogels containing borate-based bioactive glass particles and carbon-based nanopowders were designed for bone tissue engineering applications. For this purpose, mixtures of Pluronic F127 block-copolymer and 13-93B3 bioactive glass particles with different sizes (2.3 µm, 14 µm, 150 µm) were prepared in aqueous medium and their in situ gelation were investigated through rheological measurements as a function of temperature. Effects of graphene nanopowders and multi-walled carbon nanotubes on the flow behavior of the designed hydrogel system were also investigated. Results revealed that viscosity of the prepared hydrogel system was strongly dependent on the temperature and the bioactive glass particle size. Inclusion of graphene and multi-walled carbon nanotubes in this system caused a further increase in viscosity. All of the hydrogel compositions designed in the study showed shear thinning flow behavior which is a crucial parameter for injectability. Drug release studies showed that the addition of bioactive glass and carbon-based nanoparticles improved the drug release behavior of the prepared hydrogels.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. H. Ding, C.-J. Zhao, X. Cui, Y.-F. Gu, W.-T. Jia, M.N. Rahaman, Y. Wang, W.-H. Huang, C.-Q. Zhang, Novel injectable borate bioactive glass cement as an antibiotic delivery vehicle for treating osteomyelitis. PLoS ONE 9(1), e85472 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. X. Liu, X. Wang, Z. Chen, F.Z. Cui,  H.Y. Liu, K. Mao, Y. Wang, Injectable bone cement based on mineralized collagen. J. Biomed. Mater. Res. 94, 72–79 (2010)

    Google Scholar 

  3. T. Hui, X. Yongqing, Z. Tiane, L. Gang, Y. Yongqang, J. Muyao, L. Jun, D. Jing, Treatment of osteomyelitis by liposomal gentamicin-impregnated calcium sulfate. Arch. Orthop. Trauma Surg. 129, 1301–1308 (2009)

    Article  PubMed  Google Scholar 

  4. W. Jia, S.H. Luo, C.Q. Zhang, J.Q. Wang, In vitro and in vivo efficacies of teicoplanin-loaded calcium sulfate for treatment of chronic methicillin-resistant Staphylococcus aureus osteomyelitis. Antimicrob. Agents Chemother. 54, 170–176 (2010)

    Article  CAS  PubMed  Google Scholar 

  5. M.A. Rauschmann, T.A. Wichelhaus, V. Stirnal, E. Dingeldein, L. Zichner, Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections. Biomaterials 26, 2677–2684 (2005)

    Article  CAS  PubMed  Google Scholar 

  6. J.A. Killion, S. Kehoe, L.M. Geever, D.M. Devine, E. Sheehan, D. Boyd, C.L. Higginbotham, Hydrogel/bioactive glass composites for bone regeneration applications: synthesis and characterisation. Mater. Sci. Eng. C 33, 4203–4212 (2013)

    Article  CAS  Google Scholar 

  7. N.L. Elstad, K.D. Fowers, OncoGel (ReGel/paclitaxel)—clinical applications for a novel paclitaxel delivery system. Adv. Drug Deliv. Rev. 61, 785–794 (2009)

    Article  CAS  PubMed  Google Scholar 

  8. S. Nie, W.L.W. Hsiao, W. Pan, Z. Yang, Thermoreversible Pluronic® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies. Int. J. Nanomed. 6, 151–166 (2011)

    CAS  Google Scholar 

  9. J. Liaw, Y. Lin, Evaluation of poly(ethylene oxide)–poly(propylene oxide)–poly(ethylene oxide) (PEO–PPO–PEO) gels as a release vehicle for percutaneous fentanyl. J. Control. Release 68, 273–282 (2000)

    Article  CAS  PubMed  Google Scholar 

  10. P.J. Kondiah, Y.E. Choonara, P.P.D. Kondiah, T. Marimuthu, P. Kumar, L.C. du Toit, V. Pillay, A review of injectable polymeric hydrogel systems for application in bone tissue engineering. Molecules 21, 1580 (2016). https://doi.org/10.3390/molecules21111580

    Article  CAS  PubMed Central  Google Scholar 

  11. M. Bercea, S. Morariu, L.E. Nita, R.N. Darie, Investigation of poly(vinyl alcohol)/pluronic F127 physical gels. Polym.-Plast. Technol. Eng. 53, 1354–1361 (2014)

    Article  CAS  Google Scholar 

  12. L.C.P. Trong, M. Djabourov, A. Ponton, Mechanisms of micellization and rheology of PEO-PPO-PEO triblock copolymers with different architectures. J. Colloid Interfaces. Sci. 328, 278–287 (2008)

    Article  CAS  Google Scholar 

  13. K. Derakhshandeh, M. Fashi, S. Seifoleslami, Thermosensitive Pluronic® hydrogel: prolonged injectable formulation for drug abuse. Drug Des. Dev. Ther. 4, 255–262 (2010)

    Article  CAS  Google Scholar 

  14. J.J. Escobar-Chávez, M. López-Cervantes, A. Naïk, Y.N. Kalia, D. Quintanar-Guerrero, A. Ganem-Quintanar, Applications of thermoreversible Pluronic F-127 gels in pharmaceutical formulations. J. Pharm. Pharmaceut. Sci. 9, 339–358 (2006)

    Google Scholar 

  15. G. Cirillo, S. Hampel, U.G. Spizzirri, O.I. Parisi, N. Picci, F. Iemma, Carbon nanotubes hybrid hydrogels in drug delivery: a perspective review. Biomed. Res. Int. 2014, 825017 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Y.-S. Jung, W. Park, H. Parka, D.-K. Leeb, K. Na, Thermo-sensitive injectable hydrogel based on the physical mixing of hyaluronicacid and Pluronic F-127 for sustained NSAID delivery. Carbohyd. Polym. 156, 403–408 (2017)

    Article  CAS  Google Scholar 

  17. J. Clapper, J. Skeie, R. Mullins, C.A. Guymon, Development and characterization of photopolymerizable biodegradable materials from PEG–PLA–PEG block macromonomers. Polymer 48, 6554–6564 (2007)

    Article  CAS  Google Scholar 

  18. E. Lippens, G. Vertenten, J. Gironès, H. Declercq, J. Saunders, J. Luyten, L. Duchateau, E. Schacht, L. Vlaminck, F. Gasthuys, M. Cornelissen, Evaluation of bone regeneration with an injectable, in situ polymerizable Pluronic® F127 hydrogel derivative combined with autologous mesenchymal stem cells in a goat tibia defect model. Tissue Eng. Part A 16(2), 617–627 (2010)

    Article  CAS  PubMed  Google Scholar 

  19. N.S. Satarkar, D. Johnson, B. Marrs, R. Andrews, C. Poh, B. Gharaibeh, K. Saito, K.W. Anderson, J.Z. Hilt, Hydrogel-MWCNT nanocomposites: synthesis, characterization, and heating with radiofrequency fields. J. Appl. Polym. Sci. 117(3), 1813–1819 (2010)

    CAS  Google Scholar 

  20. P. Schexnailder, G. Schmidt, Nanocomposite polymer hydrogels. Colloid Polym. Sci. 287(1), 1–11 (2009)

    Article  CAS  Google Scholar 

  21. H. Hu, J. Yu, Y. Li, J. Zhao, H. Dong, Engineering of a novel pluronic F127/graphene nanohybrid for pH responsive drug delivery. J. Biomed. Mater. Res. Part A 100A, 141–148 (2012)

    Article  CAS  Google Scholar 

  22. J.S. Muñoz, U. Kettenberger, P. Procter, D.P. Pioletti, Non-setting, injectable biomaterials containing particulate hydroxyapatite can increase primary stability of bone screws in cancellous bone. Clin. Biomech. 59, 174–180 (2018)

    Article  Google Scholar 

  23. C. Pontremoli, M. Boffito, S. Fiorilli, R. Laurano, A. Torchio, A. Bari, C. Tonda-Turo, G. Ciardelli, C. Vitale-Brovarone, Hybrid injectable platforms for the in situ delivery of therapeutic ions from mesoporous glasses. Chem. Eng. J. 340, 103–113 (2018)

    Article  CAS  Google Scholar 

  24. L. Bi, S. Jung, D. Day, K. Neidig, V. Dusevich, D. Eick, L. Bonewald, Evaluation of bone regeneration, angiogenesis, and hydroxyapatite conversion in critical sized rat calvarial defects implanted with bioactive glass scaffolds. J. Biomed. Mater. Res. 100, 3267–3275 (2012)

    Article  CAS  Google Scholar 

  25. Q.Z. Chen, I.D. Thompson, A.R. Boccaccini, 45S5 Bioglass-derived glass-ceramic scaffolds for bone tissue engineering. Biomaterials 27, 2414–2425 (2006)

    Article  CAS  PubMed  Google Scholar 

  26. L.L. Hench, R.J. Splinter, W.C. Allen, T.K. Greenlee, Bonding mechanisms at the interface of ceramic prosthetic materials. J. Biomed. Mater. Res. 5, 117–141 (1971)

    Article  Google Scholar 

  27. E. Fiume, J. Barberi, E. Verné, F. Baino, Bioactive glasses: from parent 45S5 composition to scaffold-assisted tissue-healing therapies. J. Funct. Biomater. 9, 24 (2018). https://doi.org/10.3390/jfb9010024

    Article  CAS  PubMed Central  Google Scholar 

  28. M. Brink, The influence of alkali and alkaline earths on the working range for bioactive glasses. J. Biomed. Mater. Res. 36(1), 109–117 (1997)

    Article  CAS  PubMed  Google Scholar 

  29. F. Baino, S. Hamzehlou, S. Kargozar, Bioactive glasses: where are we and where are we going? J. Funct. Biomater. 9, 25 (2018)

    Article  CAS  PubMed Central  Google Scholar 

  30. W. Liang, M.N. Rahaman, D.E. Day, N.W. Marion, G.C. Riley, J.J. Mao, Bioactive borate glass scaffold for bone tissue engineering. J. Non-Cryst. Solids 354, 1690–1696 (2008)

    Article  CAS  Google Scholar 

  31. H. Fu, Q. Fu, N. Zhou, W. Huang, M.N. Rahaman, D. Wang, X. Liu, In vitro evaluation of borate-based bioactive glass scaffolds prepared by a polymer foam replication method. Mater. Sci. Eng. C 29, 2275–2281 (2009)

    Article  CAS  Google Scholar 

  32. M.N. Rahaman, D.E. Day, B.S. Bal, Q. Fu, S.B. Jung, L.F. Bonewalde, A.P. Tomsia, Bioactive glass in tissue engineering. Acta Biomater. 7, 2355–2373 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. S. Naseri, W.C. Lepry, S.N. Nazhat, Bioactive glasses in wound healing: hope or hype? J. Mater. Chem. B 5, 6167–6174 (2017)

    Article  CAS  PubMed  Google Scholar 

  34. X. Cui, Y. Zhang, H. Wang, Y. Gu, L. Li, J. Zhou, S. Zhao, W. Huang, N. Zhou, D. Wang, H. Pan, M.N. Rahaman, An injectable borate bioactive glass cement for bone repair: preparation, bioactivity and setting mechanism. J. Non-Cryst. Solids 432, 150–157 (2016)

    Article  CAS  Google Scholar 

  35. G. Jin, K. Li, The electrically conductive scaffold as the skeleton of stem cell niche in regenerative medicine. Mater. Sci. Eng. C 45, 671–681 (2014)

    Article  CAS  Google Scholar 

  36. M. Türk, A.M. Deliormanlı, Electrically conductive porous borate-based bioactive glass scaffolds for bone tissue engineering applications. J. Biomater. Appl. 32(1), 28–39 (2017)

    Article  CAS  PubMed  Google Scholar 

  37. B. Li, L. Zhang, Z. Zhang, R. Gao, H. Li, Z. Dong, Q. Wang, Q. Zhou, Y. Wang, Physiologically stable F127-GO supramolecular hydrogel with sustained drug release characteristic for chemotherapy and photothermal therapy. RSC Adv. 8, 1693–1699 (2018)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. A. Yao, D. Wang, W. Huang, Q. Fu, M.N. Rahaman, D.E. Day, In vitro bioactive characteristics of borate-based glasses with controllable degradation behavior. J. Am. Ceram. Soc. 90(1), 303–306 (2007)

    Article  CAS  Google Scholar 

  39. T. Kokubo, H. Kushitani, S. Sakka, T. Kitsugi, T. Yamamuro, Solutions able to reproduce in vivo surface-structure changes in bioactive glass-ceramic A-W. J. Biomed. Mater. Res. 24, 721–734 (1990)

    Article  CAS  PubMed  Google Scholar 

  40. K. Kurumada, B.H. Robinson, Viscosity studies of Pluronic F127 in aqueous solution. Progr. Colloid Polm. Sci. 123, 12–15 (2004)

    CAS  Google Scholar 

  41. M.T. Cidade, D.J. Ramos, J. Santos, H. Carrelo, N. Calero, J.P. Borges, Injectable hydrogels based on Pluronic/water systems filled with alginate microparticles for biomedical applications. Materials 12, 1083 (2019). https://doi.org/10.3390/ma12071083

    Article  CAS  PubMed Central  Google Scholar 

  42. B.K. Lau, Q. Wang, W. Sun, L. Li, Micellization to gelation of a triblock copolymer in water: thermoreversibility and scaling. J. Polym. Sci. B 42, 2014–2025 (2004)

    Article  CAS  Google Scholar 

  43. A. Peigney, C. Laurent, E. Flahaut, R.R. Bacsa, A. Rousset, Specific surface area of carbon nanotubes and bundles of carbon nanotubes. Carbon 39(4), 507–514 (2001)

    Article  CAS  Google Scholar 

  44. M. Guvendiren, H.D. Lua, J.A. Burdick, Shear-thinning hydrogels for biomedical applications. Soft Matter 8, 260–272 (2012). https://doi.org/10.1039/C1SM06513K

    Article  CAS  Google Scholar 

  45. X. Xu, S.A. Rice, A.R. Dinner, Relation between ordering and shear thinning in colloidal suspensions. Proc. Natl. Acad. Sci. 110(10), 3771–3776 (2013). https://doi.org/10.1073/pnas.1301055110

    Article  PubMed  PubMed Central  Google Scholar 

  46. A. Vázquez-Quesada, R.I. Tanner, M. Ellero, Shear thinning of noncolloidal suspensions. Phys. Rev. Lett. 117, 108001 (2016)

    Article  PubMed  Google Scholar 

  47. Y. Ryabenkova, A. Pinnock, P.A. Quadros, R.L. Goodchild, G. Möbus, A. Crawford, P.V. Hatton, C.A. Miller, The relationship between particle morphology and rheological properties in injectable nano-hydroxyapatite bone graft substitutes. Mater. Sci. Eng. 75, 1083–1090 (2017)

    Article  CAS  Google Scholar 

  48. H.A. Barnes, J.F. Hutton, K. Walters, An Introduction to Rheology, 1st edn. (Elsevier, Amsterdam, 1989)

    Google Scholar 

  49. D.B. Genovese, Shear rheology of hard-sphere, dispersed, and aggregated suspensions, and filler-matrix composites. Adv. Colloid Interface 171–172, 1–16 (2012)

    Article  CAS  Google Scholar 

  50. S.K. Kawatra, T.C. Eisele, Rheological effects in grinding circuits. Int. J. Miner. Process. 22, 251–259 (1988)

    Article  CAS  Google Scholar 

  51. N. Mangesana, R.S. Chikuku, A.N. Mainza, I. Govender, A.P. van der Westhuizen, M. Narashima, The effect of particle sizes and solids concentration on the rheology of silica sand based suspensions. J. S. Afr. Inst. Min. Metall. 108, 237–243 (2008)

    CAS  Google Scholar 

  52. P.F. Luckham, M.A. Ukeje, Effect of particle size distribution on the rheology of dispersed systems. J. Colloid Interfaces Sci. 220, 347–356 (1999)

    Article  CAS  Google Scholar 

  53. Z. Zhou, M.J. Solomon, P.J. Scales, D.V. Boger, The yield stress of concentrated flocculated suspensions of size distributed particles. J. Rheol. 43, 651 (1999). https://doi.org/10.1122/1.551029

    Article  CAS  Google Scholar 

  54. R.J. Farris, Prediction of the viscosity of multimodal suspensions from unimodal viscosity data. Trans. Soc. Rheol. 12, 281–301 (1968)

    Article  Google Scholar 

  55. C. Ancey, Role of lubricated contacts in concentrated polydisperse suspensions. J. Rheol. 45, 1421–1439 (2001). https://doi.org/10.1122/1.1413504

    Article  CAS  Google Scholar 

  56. W. Pabst, E. Gregorova, C. Berthold, Particle shape and suspension rheology of short-fiber systems. J. Eur. Ceram. Soc. 26, 149–160 (2006). https://doi.org/10.1016/j.jeurceramsoc.2004.10.016

    Article  CAS  Google Scholar 

  57. B. Klein, S.J. Partridge, J.S. Laskowski, Influence of physicomechanical properties on the rheology and stability of magnetite dense media, Production and Processing of Fine Particles, Canadian Institute of Mining and Metallurgy, ed by A.J. Plumpton, (1988)

  58. Y.V. Shtogun, L.M. Woods, Many-body van der waals interactions between graphitic nanostructures. J. Phys. Chem. Lett. 1, 1356–1362 (2010). https://doi.org/10.1021/jz100309m

    Article  CAS  Google Scholar 

  59. V.V. Gobre, A. Tkatchenko, Scaling laws for van der Waals interactions in nanostructured materials. Nat. Commun. 4, 2341 (2013). https://doi.org/10.1038/ncomms3341

    Article  PubMed  Google Scholar 

  60. R. Atif, F. Inam, Reasons and remedies for the agglomeration of multilayered graphene and carbon nanotubes in polymers. Beilstein J. Nanotechnol. 7, 1174–1196 (2016). https://doi.org/10.3762/bjnano.7.109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. O.V. Kharissova, B.I. Kharisov, E.G. de Casas Ortiz, Dispersion of carbon nanotubes in water and non-aqueous solvents. RSC Adv. 3, 24812 (2013)

    Article  CAS  Google Scholar 

  62. M. Bohner, G. Baroud, Injectability of calcium phosphate pastes. Biomaterials 26, 1553–1563 (2005)

    Article  CAS  PubMed  Google Scholar 

  63. R. O’Neill, H.O. McCarthy, E. Montufar, M.-P. Ginebra, D.I. Wilson, A. Lennon, N. Dunne, Critical review: injectability of calcium phosphate pastes and cements. Acta Biomater. 50, 1–19 (2017)

    Article  CAS  PubMed  Google Scholar 

  64. M. Farrugia, S.P. Morgan, C. Alexander, M.L. Mather, Ultrasonic monitoring of drug loaded Pluronic F127 micellular hydrogel phase behaviour. Mater. Sci. Eng. C 34, 280–286 (2014)

    Article  CAS  Google Scholar 

  65. Q.M. Jiang, Y.F. Fan, C.S. Tao, The experiment of stability of gentamycin sulfate mixture. Med. J. Commun. 16, 291–292 (2002)

    Google Scholar 

  66. S. Chen, L. Ge, A. Mueller, M.A. Carlson, M.J. Teusink, F.D. Shuler, J. Xie, Twisting electrospun nanofiber fine strips into functional sutures for sustained co-delivery of gentamicin and silver. Nanomedicine 13(4), 1435–1445 (2017). https://doi.org/10.1016/j.nano.2017.01.016

    Article  CAS  PubMed  Google Scholar 

  67. M.Y. Krasko, J. Golenser, A. Nyska, M. Nyska, Y.S. Brin, A.J. Domb, Gentamicin extended release from an injectable polymeric implant. J. Controll. Release 117, 90–96 (2007)

    Article  CAS  Google Scholar 

  68. J. Liu, L. Cui, D. Losic, Graphene and graphene oxide as new nanocarriers for drug delivery application. Acta Biomater. 9(12), 9243–9257 (2013)

    Article  CAS  PubMed  Google Scholar 

  69. A.M.A. Elhissi, W. Ahmed, I. Ul Hassan, V.R. Dhanak, A. D’Emanuele, Carbon nanotubes in cancer therapy and drug delivery. J. Drug Deliv. 2012, 837327 (2012)

    Article  CAS  PubMed  Google Scholar 

  70. L. Saeednia, L. Yao, K. Cluff, R. Asmatulu, Sustained releasing of methotrexate from injectable and thermosensitive chitosan–carbon nanotube hybrid hydrogels effectively controls tumor cell growth. ACS Omega 4(2), 4040–4048 (2019)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. H. Pandey, V. Parashar, R. Parashar, R. Prakash, P.W. Ramteke, A.C. Pandey, Controlled drug release characteristics and enhanced antibacterial effect of graphene nanosheets containing gentamicin sulfate. Nanoscale 3, 4104–4108 (2011)

    Article  CAS  PubMed  Google Scholar 

  72. Z. Xie, X. Cui, C. Zhao, W. Huang, J. Wang, C. Zhang, Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model. Antimicrob. Agents Chemother. 57(7), 3293–3298 (2013). https://doi.org/10.1128/AAC.00284-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Q. Fu, M.N. Rahaman, H. Fu, X. Liu, Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation. J. Biomed. Mater. Res. A 95A, 164–171 (2010)

    Article  CAS  Google Scholar 

  74. A.M. Deliormanlı, Size dependent degradation behavior of borate bioactive glass. Ceram. Int. 39(7), 8087–8095 (2013)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The financial support for this research was provided by the Scientific and Technical Research Council of Turkey (TUBITAK), 1001 grant program for scientific and technological research projects; Project No: 114M519.

Author information

Authors and Affiliations

  1. Department of Metallurgical and Materials Engineering, Faculty of Engineering, Manisa Celal Bayar University, Yunusemre, 45140, Manisa, Turkey

    Aylin M. Deliormanlı & Mert Türk

Authors
  1. Aylin M. Deliormanlı
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mert Türk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Aylin M. Deliormanlı.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Deliormanlı, A.M., Türk, M. Flow Behavior and Drug Release Study of Injectable Pluronic F-127 Hydrogels containing Bioactive Glass and Carbon-Based Nanopowders. J Inorg Organomet Polym 30, 1184–1196 (2020). https://doi.org/10.1007/s10904-019-01346-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10904-019-01346-2

Keywords

Search

Navigation