Skip to main content

Advertisement

SpringerLink
Log in

Ciprofloxacin-loaded polymeric nanoparticles incorporated electrospun fibers for drug delivery in tissue engineering applications

  • Original Article
  • Published:
Drug Delivery and Translational Research Aims and scope Submit manuscript

Abstract

Presented work focuses on the development of biodegradable polymer nanoparticles loaded with antibiotics as drug delivery systems deposited on electrospun scaffolds for tissue engineering. The innovative ciprofloxacin-loaded poly(dl-lactide-co-glycolide) NPs ensure a continuous slow release and high local concentration at the site of action for an optimal therapy. The local delivery of antibiotics as an integrated part of electrospun scaffolds offers an effective, safe, and smart enhancement supporting tissue regeneration. Presented data provides solid scientific evidence for fulfilling the requirements of local nano antibiotic delivery systems with biodegradability and biocompatibility for a wide range of tissue engineering applications, including middle ear tissues (e.g., tympanic membranes) which are subject to bacterial infections. Further characterization of such systems, including in vivo studies, is required to ensure successful transfer from lab to clinical applications.

.

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
Fig. 11
Fig. 12
Fig. 13
Fig. 14

Similar content being viewed by others

Notes

  1. Breakpoint tables for interpretation of MICs and zone diameters, in the European Committee on Antimicrobial Susceptibility Testing, 2014.

References

  1. Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnol. 2018;16(1):71. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30231877. Accessed Jan 2020.

  2. Goyal R, Macri LK, Kaplan HM, Kohn J. Nanoparticles and nanofibers for topical drug delivery. J Control Release. 2016;240:77–92. Available from: http://www.sciencedirect.com/science/article/pii/S0168365915302157. Accessed Jan 2020.

  3. Ulbrich K, Hola K, Subr V, Bakandritsos A, Tucek J, Zboril R. Targeted drug delivery with polymers and magnetic nanoparticles: covalent and noncovalent approaches, release control, and clinical studies. Chem Rev. 2016;116(9):5338–431.

    Article  CAS  PubMed  Google Scholar 

  4. Langer R, Vacanti JP. Tissue engineering. Science. 1993;260(5110):920–6.

    Article  CAS  PubMed  Google Scholar 

  5. Moroni L, Boland T, Burdick JA, De Maria C, Derby B, Forgacs G, et al. Biofabrication: a guide to technology and terminology. Trends Biotechnol. 2018;36(4):384–402. Available from: http://www.sciencedirect.com/science/article/pii/S0167779917302792. Accessed Jan 2020.

  6. Choudhury D, Anand S, Naing MW. The arrival of commercial bioprinters—towards 3D bioprinting revolution! Int J Bioprinting. 2018;4(2). https://doi.org/10.18063/ijb.v4i2139 Available from: http://ijb.whioce.com/index.php/int-j-bioprinting/article/view/139. Accessed Jan 2020.

  7. Dersch R, Graeser M, Greiner A, Wendorff JH. Electrospinning of nanofibres: towards new techniques, functions, and applications. Aust J Chem. 2007;60(10):719–28. https://doi.org/10.1071/CH07082.

    Article  CAS  Google Scholar 

  8. Bhardwaj N, Kundu SC. Electrospinning: a fascinating fiber fabrication technique. Biotechnol Adv. 2010;28(3):325–47.

    Article  CAS  PubMed  Google Scholar 

  9. Danti S, Mota C, D’alessandro D, Trombi L, Ricci C, Redmond SL, et al. Tissue engineering of the tympanic membrane using electrospun PEOT/PBT copolymer scaffolds: a morphological in vitro study. Hear Balanc Commun. 2015;13(4):133–47. https://doi.org/10.3109/21695717.2015.1092372.

    Article  Google Scholar 

  10. Mota C, Danti S, D’Alessandro D, Trombi L, Ricci C, Puppi D, et al. Multiscale fabrication of biomimetic scaffolds for tympanic membrane tissue engineering. Biofabrication. 2015;7(2):25005.

    Article  Google Scholar 

  11. Sundaramurthi D, Krishnan UM, Sethuraman S. Electrospun nanofibers as scaffolds for skin tissue engineering. Polym Rev. 2014;54(2):348–76. https://doi.org/10.1080/15583724.2014.881374.

    Article  CAS  Google Scholar 

  12. Alves da Silva ML, Martins A, Costa-Pinto AR, Costa P, Faria S, Gomes M, et al. Cartilage tissue engineering using electrospun PCL nanofiber meshes and MSCs. Biomacromolecules. 2010;11(12):3228–36.

    Article  CAS  PubMed  Google Scholar 

  13. Wang Z, Wang Z, Lu WW, Zhen W, Yang D, Peng S. Novel biomaterial strategies for controlled growth factor delivery for biomedical applications. NPG Asia Mater. 2017;9(10):e435. https://doi.org/10.1038/am.2017.171.

    Article  CAS  Google Scholar 

  14. Sakai R, John B, Okamoto M, Seppälä JV, Vaithilingam J, Hussein H, et al. Fabrication of polylactide-based biodegradable thermoset scaffolds for tissue engineering applications. Macromol Mater Eng. 2013;298(1):45–52. https://doi.org/10.1002/mame.201100436.

    Article  CAS  Google Scholar 

  15. Prabaharan M, Sivashankari PR. Prospects of bioactive chitosan-based scaffolds in tissue engineering and regenerative medicine BT—chitin and chitosan for regenerative medicine. In: Dutta PK, editor. . New Delhi: Springer India; 2016. p. 41–59. https://doi.org/10.1007/978-81-322-2511-9_2.

    Chapter  Google Scholar 

  16. Malafaya PB, Silva GA, Reis RL. Natural-origin polymers as carriers and scaffolds for biomolecules and cell delivery in tissue engineering applications. Adv Drug Deliv Rev. 2007;59(4–5):207–33.

    Article  CAS  PubMed  Google Scholar 

  17. O’Brien FJ. Biomaterials & scaffolds for tissue engineering. Mater Today. 2011;14(3):88–95. Available from: http://www.sciencedirect.com/science/article/pii/S136970211170058X. Accessed Jan 2020.

  18. Nagarajan S, Bechelany M, Kalkura NS, Miele P, Bohatier CP, Balme S. Chapter 20. Electrospun nanofibers for drug delivery in regenerative medicine. In: Mohapatra SS, Ranjan S, Dasgupta N, Mishra RK, Thomas SBT-A of TND and DS, editors. Micro and nano technologies. Elsevier; 2019. p. 595–625. Available from: http://www.sciencedirect.com/science/article/pii/B978012814029100020X. Accessed Jan 2020.

  19. Babitha S, Rachita L, Karthikeyan K, Shoba E, Janani I, Poornima B, et al. Electrospun protein nanofibers in healthcare: a review. Int J Pharm. 2017;523(1):52–90.

    Article  CAS  PubMed  Google Scholar 

  20. Buck E, Maisuria V, Tufenkji N, Cerruti M. Antibacterial properties of PLGA electrospun scaffolds containing ciprofloxacin incorporated by blending or physisorption. ACS Appl Bio Mater. 2018;1(3):627–35. https://doi.org/10.1021/acsabm.8b00112.

    Article  CAS  Google Scholar 

  21. Xu X, Zhong W, Zhou S, Trajtman A, Alfa M. Electrospun PEG–PLA nanofibrous membrane for sustained release of hydrophilic antibiotics. J Appl Polym Sci. 2010;118(1):588–95. https://doi.org/10.1002/app.32415.

    Article  CAS  Google Scholar 

  22. Qi R, Guo R, Zheng F, Liu H, Yu J, Shi X. Controlled release and antibacterial activity of antibiotic-loaded electrospun halloysite/poly(lactic-co-glycolic acid) composite nanofibers. Colloids Surfaces B Biointerfaces. 2013;110:148–55. Available from: http://www.sciencedirect.com/science/article/pii/S0927776513002944. Accessed Jan 2020.

  23. Zhang Z, Tang J, Wang H, Xia Q, Xu S, Han CC. Controlled antibiotics release system through simple blended electrospun fibers for sustained antibacterial effects. Vol. 7, ACS Applied Materials & Interfaces. United States; 2015. p. 26400–4.

  24. Vinatier C, Guicheux J. Cartilage tissue engineering: from biomaterials and stem cells to osteoarthritis treatments. Ann Phys Rehabil Med. 2016;59(3):139–44. Available from: http://www.sciencedirect.com/science/article/pii/S187706571630001X. Accessed Jan 2020.

  25. Qu H, Fu H, Han Z, Sun Y. Biomaterials for bone tissue engineering scaffolds: a review. RSC Adv. 2019;9(45):26252–62. https://doi.org/10.1039/C9RA05214C.

    Article  CAS  Google Scholar 

  26. Günday Türeli N, Türeli AE, Schneider M. Optimization of ciprofloxacin complex loaded PLGA nanoparticles for pulmonary treatment of cystic fibrosis infections: design of experiments approach. Int J Pharm. 2016;515(1):343–51. Available from: http://www.sciencedirect.com/science/article/pii/S0378517316309590. Accessed Jan 2020.

  27. Draheim C, de Crecy F, Hansen S, Collnot E-M, Lehr C-M. A design of experiment study of nanoprecipitation and nano spray drying as processes to prepare PLGA nano- and microparticles with defined sizes and size distributions. Pharm Res. 2015;32(8):2609–24.

    CAS  PubMed  Google Scholar 

  28. Havel H, Finch G, Strode P, Wolfgang M, Zale S, Bobe I, et al. Nanomedicines: from bench to bedside and beyond. AAPS J. 2016;18(6):1373–8.

    Article  CAS  PubMed  Google Scholar 

  29. Caster JM, Patel AN, Zhang T, Wang A. Investigational nanomedicines in 2016: a review of nanotherapeutics currently undergoing clinical trials. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017;9(1).

  30. Ventola CL. Progress in nanomedicine: approved and investigational nanodrugs. P T. 2017;42(12):742–55. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29234213. Accessed Jan 2020.

  31. Primavessy D, Günday Türeli N, Schneider M. Influence of different stabilizers on the encapsulation of desmopressin acetate into PLGA nanoparticles. Eur J Pharm Biopharm. 2017;118:48–55. Available from: http://www.sciencedirect.com/science/article/pii/S0939641116309638. Accessed Jan 2020.

  32. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release. 2001;70(1–2):1–20.

    Article  CAS  PubMed  Google Scholar 

  33. Günday Türeli N, Türeli AE. Good manufacturing practices (GMP) of magnetic nanoparticles. In: Thanh NTK, editor. Clinical applications of magnetic nanoparticles. Boca Raton London New York: CRC Press, Taylor and Francis; 2018. p. 473–82.

    Google Scholar 

  34. Wacker M. Nanocarriers for intravenous injection—the long hard road to the market. Int J Pharm. 2013;457(1):50–62.

    Article  CAS  PubMed  Google Scholar 

  35. Torge A, Wagner S, Chaves PS, Oliveira EG, Guterres SS, Pohlmann AR, et al. Ciprofloxacin-loaded lipid-core nanocapsules as mucus penetrating drug delivery system intended for the treatment of bacterial infections in cystic fibrosis. Int J Pharm. 2017;527(1):92–102. Available from: http://www.sciencedirect.com/science/article/pii/S0378517317304234. Accessed Jan 2020.

  36. Günday Türeli N, Torge A, Juntke J, Schwarz BC, Schneider-Daum N, Türeli AE, et al. Ciprofloxacin-loaded PLGA nanoparticles against cystic fibrosis P. aeruginosa lung infections. Eur J Pharm Biopharm. 2017;117:363–71 Available from: http://www.sciencedirect.com/science/article/pii/S0939641116309924. Accessed January, 2020.

    Article  PubMed  Google Scholar 

  37. Zhu Z, Anacker JL, Ji S, Hoye TR, Macosko CW, Prud’homme RK. Formation of block copolymer-protected nanoparticles via reactive impingement mixing. Langmuir. 2007;23(21):10499–504.

    Article  CAS  PubMed  Google Scholar 

  38. Zhao C-X, He L, Qiao SZ, Middelberg APJ. Nanoparticle synthesis in microreactors. Chem Eng Sci. 2011;66(7):1463–79. Available from: http://www.sciencedirect.com/science/article/pii/S0009250910005142. Accessed Jan 2020.

  39. Goyal U, Arora R, Aggarwal G. Formulation design and evaluation of a self-microemulsifying drug delivery system of lovastatin. Acta Pharma. 2012;62(3):357–70.

    Article  CAS  Google Scholar 

  40. Gunday Tureli N, Tureli AE, Schneider M. Counter-ion complexes for enhanced drug loading in nanocarriers: proof-of-concept and beyond. Int J Pharm. 2016;511(2):994–1001.

    Article  PubMed  Google Scholar 

  41. Brannon-Peppas L. Recent advances on the use of biodegradable microparticles and nanoparticles in controlled drug delivery. Int J Pharm. 1995;116(1):1–9. Available from: http://www.sciencedirect.com/science/article/pii/037851739400324X. Accessed Jan 2020.

  42. Filkins LM, O’Toole GA. Cystic fibrosis lung infections: polymicrobial, complex, and hard to treat. PLoS Pathog. 2015;11(12):e1005258. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26719892. Accessed Jan 2020.

  43. Pichichero ME. Otitis media. Pediatr Clin N Am. 2013;60(2):391–407.

    Article  Google Scholar 

  44. Kumari A, Yadav SK, Yadav SC. Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B Biointerfaces. 2010;75(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  45. Sinha VR, Bansal K, Kaushik R, Kumria R, Trehan A. Poly-ϵ-caprolactone microspheres and nanospheres: an overview. Int J Pharm. 2004;278(1):1–23. Available from: http://www.sciencedirect.com/science/article/pii/S0378517304001693. Accessed Jan 2020.

  46. Woodruff MA, Hutmacher DW. The return of a forgotten polymer—polycaprolactone in the 21st century. Prog Polym Sci. 2010;35(10):1217–56. Available from: http://www.sciencedirect.com/science/article/pii/S0079670010000419. Accessed Jan 2020.

  47. Espinoza SM, Patil HI, San Martin Martinez E, Casañas Pimentel R, Ige PP. Poly-ε-caprolactone (PCL), a promising polymer for pharmaceutical and biomedical applications: focus on nanomedicine in cancer. Int J Polym Mater Polym Biomater. 2020;69(2):85–126. https://doi.org/10.1080/00914037.2018.1539990.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

The authors would like to thank Ms. Lara Bayer for her technical assistance at MJR PharmJet GmbH labs, and Mr. Pratik Bachhav for his graphical assistance at Maastricht University.

Funding

The authors acknowledge the 4NanoEARDRM project funded under the frame of EuroNanoMed III.

Author information

Author notes

  1. Cemre Günday and Shivesh Anand equally contributed to this research article.

Authors and Affiliations

  1. MJR PharmJet GmbH, Industriestr. 1B, 66802, Überherrn, Germany

    Cemre Günday, Nazende Günday Türeli & Akif Emre Türeli

  2. MERLN Institute for Technology-Inspired Regenerative Medicine, Department of Complex Tissue Regeneration, Maastricht University, 6229 ER, Maastricht, The Netherlands

    Shivesh Anand, Sara Munafò, Lorenzo Moroni & Carlos Mota

  3. Department of Biomedical Engineering, Istanbul Arel University, 34537, İstanbul, Turkey

    Hikmet Burcu Gencer & Pinar Cakir Hatir

  4. Department of Civil and Industrial Engineering, University of Pisa, 56122, Pisa, Italy

    Sara Munafò & Serena Danti

  5. Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, 80138, Naples, Italy

    Alessandra Fusco & Giovanna Donnarumma

  6. Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM), Florence, Italy

    Alessandra Fusco, Giovanna Donnarumma, Claudio Ricci & Serena Danti

Authors
  1. Cemre Günday
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shivesh Anand
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hikmet Burcu Gencer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sara Munafò
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lorenzo Moroni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Alessandra Fusco
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovanna Donnarumma
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Claudio Ricci
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Pinar Cakir Hatir
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Nazende Günday Türeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Akif Emre Türeli
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Carlos Mota
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Serena Danti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nazende Günday Türeli.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

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

Electronic supplementary material

ESM 1

(PPTX 7913 kb)

ESM 2

(PPTX 1131 kb)

ESM 3

(PPTX 878 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Günday, C., Anand, S., Gencer, H.B. et al. Ciprofloxacin-loaded polymeric nanoparticles incorporated electrospun fibers for drug delivery in tissue engineering applications. Drug Deliv. and Transl. Res. 10, 706–720 (2020). https://doi.org/10.1007/s13346-020-00736-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13346-020-00736-1

Keywords

Search

Navigation