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Bi-layered disulfiram-loaded fiber membranes with antibacterial properties for wound dressing

Applied Biochemistry and Biotechnology volume 194, pages 1359–1372 (2022)Cite this article

Abstract

In this study, the bi-layered disulfiram-loaded fiber membranes with the antibacterial activity and different surface wettabilities are prepared using electrospinning technology. In the application of wound dressing, the hydrophilic surface of fiber membranes is beneficial for cell adhesion and drug release to heal the wound. Meanwhile, the outside hydrophobic surface is able to block water penetration to reduce the probability of wound infection. The obtained bi-layered drug-loaded fiber membranes are composed of polyvinylidene fluoride (PVDF) bottom surface and disulfiram (DSF)/polylactic acid (PLA) top surface. To modify the top surface wettability, the oxygen plasma modification of bi-layered membranes was carried out. The morphology, wettability, and chemical compositions of bi-layered drug-loaded fiber membranes were analyzed using the scanning electronic microscope (SEM), drop shape analysis instrument, X-ray diffractometer (XRD), and X-ray photoelectron spectrometer (XPS). The bi-layered disulfiram-loaded membranes showed the potent antibacterial activity in vitro against both Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive). It was found that the bi-layered membranes had good biocompatibility with L929 cells. Thus, the obtained bi-layered disulfiram-loaded fiber membranes are suitable for wound dressing application.

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Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. Wang, C., & Wang, M. (2014). Electrospun multifunctional tissue engineering scaffolds. Frontiers of Materials Science, 8(1), 3–19.

    CAS  Article  Google Scholar 

  2. Zhang, J. G., & Xiumei, M. O. (2013). Current research on electrospinning of silk fibroin and its blends with natural and synthetic biodegradable polymers. Frontiers of Materials Science, 7(2), 129–142.

    CAS  Article  Google Scholar 

  3. Sun, B., Long, Y. Z., Zhang, H. D., Li, M. M., & Yin, H. L. (2014). Advances in three-dimensional nanofibrous macrostructures via electrospinning. Progress in Polymer Science, 39(5), 862–890.

    CAS  Article  Google Scholar 

  4. Zhao, J., Ho, K. K. C., Shamsuddin, S. R., Bismarck, A., & Dutschk, V. (2012). A comparative study of fibre/matrix interface in glass fibre reinforced polyvinylidene fluoride composites. Colloids & Surfaces A: Physicochemical & Engineering Aspects, 413, 58–64.

    CAS  Article  Google Scholar 

  5. Chen, D. W., Liao, J. Y., Liu, S. J., & Chan, E. C. (2012). Novel biodegradable sandwich-structured nanofibrous drug-eluting membranes for repair of infected wounds: An in vitro and in vivo study. International Journal of Nanomedicine, 7, 763–771.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Li, W., Li, X., Chen, Y., Li, X., Deng, H., Wang, T., Huang, R., & Fan, G. (2013). Poly(vinyl alcohol)/sodium alginate/layered silicate based nanofibrous mats for bacterial inhibition. Carbohydrate Polymers, 92(2), 2232–2238.

    CAS  Article  Google Scholar 

  7. Li, J., Hu, Y., He, T., Huang, M., Zhang, X., Yuan, J., Wei, Y., Dong, X., Liu, W., Ko, F., & Zhou, W. (2018). Electrospun sandwich-structure composite membranes for wound dressing scaffolds with high antioxidant and antibacterial activity. Macromolecular Materials and Engineering, 303, 1700270.

    Article  Google Scholar 

  8. Li, X., Cheng, R., Sun, Z., Su, W., Pan, G., Zhao, S., Zhao, J., & Cui, W. (2017). Flexible bipolar nanofibrous membranes for improving gradient microstructure in tendon-to-bone healing. Acta Biomaterialia, 61, 204–216.

    CAS  Article  Google Scholar 

  9. Rieger, K. A., Birch, N. P., & Schiffman, J. D. (2013). Designing electrospun nanofiber mats to promote wound healing-a review. Journal of Materials Chemistry B, 1(36), 4531–4541.

    CAS  Article  Google Scholar 

  10. Unnithan, A. R., Barakat, N., Pichiah, P. T., Gnanasekaran, G., Nirmala, R., Cha, Y. S., Jung, C. H., Mohamed, E., & Kim, H. Y. (2012). Wound-dressing materials with antibacterial activity from electrospun polyurethane-dextran nanofiber mats containing ciprofloxacin HCL. Carbohydrate Polymers, 90(4), 1786–1793.

    CAS  Article  Google Scholar 

  11. Safdari, M., Shakiba, E., Kiaie, S. H., & Fattahi, A. (2016). Preparation and characterization of ceftazidime loaded electrospun silk fibroin/gelatin mat for wound dressing. Fibers & Polymers, 17(5), 744–750.

    CAS  Article  Google Scholar 

  12. Khamforoush, M., Pirouzram, O., & Hatami, T. (2015). The evaluation of thin film composite membrane composed of an electrospun polyacrylonitrile nanofibrous mid-layer for separating oil–water mixture. Desalination, 359, 14–21.

    CAS  Article  Google Scholar 

  13. Cui, J., Qiu, L., Qiu, Y., Wang, Q., & Wei, Q. (2015). Co-electrospun nanofibers of pva-sbq and zein for wound healing. Journal of Applied Polymer Science, 132(39).

  14. Zhao, R., Li, X., Sun, B., Tong, Y., Jiang, Z., & Wang, C. (2015). Nitrofurazone-loaded electrospun PLLA/sericin-based dual-layer fiber mats for wound dressing applications. RSC Advances, 5, 16940–16949.

    CAS  Article  Google Scholar 

  15. Miguel, S., Simões, D., Moreira, A., Sequeira, R., & Correia, I. (2019). Production and characterization of electrospun silk fibroin based asymmetric membranes for wound dressing applications. International Journal of Biological Macromolecules, 121, 524–535.

    CAS  Article  Google Scholar 

  16. Aragón, J., Costa, C., Coelhoso, I., Mendoza, G., Aguiar-Ricardo, A., & Irusta, S. (2019). Electrospun asymmetric membranes for wound dressing applications. Materials Science and Engineering: C, 103, 109822.

    Article  Google Scholar 

  17. Li, X., Wang, C., Yang, S., Liu, P., & Zhang, B. (2018). Electrospun PCL/mupirocin and chitosan/lidocaine hydrochloride multifunctional double layer nanofibrous scaffolds for wound dressing applications. International journal of nanomedicine, 13, 5287.

    CAS  Article  Google Scholar 

  18. Iljin, K., Ketola, K., Vainio, P., Halonen, P., Kohonen, P., Fey, V., Grafström, R. C., Perälä, M., & Kallioniemi, O. (2009). High-throughput cell-based screening of 4910 known drugs and drug-like small molecules identifies disulfiram as an inhibitor of prostate cancer cell growth. Clinical Cancer Research, 15(19), 6070–6078.

    CAS  Article  Google Scholar 

  19. Thakare, R., Shukla, M., Kaul, G., Dasgupta, A., & Chopra, S. (2019). Repurposing disulfiram for treatment of staphylococcus aureus infections. International Journal of Antimicrobial Agents, 53(6), 709–715.

    CAS  Article  Google Scholar 

  20. Horita, Y., Takii, T., Yagi, T., Ogawa, K., Fujiwara, N., Inagaki, E., Kremer, L., Sato, Y., Kuroishi, R., Lee, Y., Makino, T., Mizukami, H., Hasegawa, T., Yamamoto, R., & Onozaki, K. (2012). Antitubercular activity of disulfiram, an antialcoholism drug, against multidrug-and extensively drug-resistant Mycobacterium tuberculosis isolates. Antimicrobial Agents and Chemotherapy, 56(8), 4140–4145.

    CAS  Article  Google Scholar 

  21. Long, & Timothy, E. (2017). Repurposing thiram and disulfiram as antibacterial agents for multidrug-resistant staphylococcus aureus infections. Antimicrobial Agents & Chemotherapy, 61(9).

  22. Xie, C., Ding, R., Wang, X., Hu, C., Yan, J., Zhang, W., Wang, Y., Qu, Y., Zhang, S., He, P., & Wang, Z. (2020). A disulfiram-loaded electrospun poly(vinylidene fluoride) nanofibrous scaffold for cancer treatment. Nanotechnology, 31(11).

  23. Zhuo, X., Lei, T., Miao, L., Chu, W., Li, X., Luo, L., Gou, J., Zhang, Y., Yin, T., He, H., & Tang, X. (2018). Disulfiram-loaded mixed nanoparticles with high drug-loading and plasma stability by reducing the core crystallinity for intravenous delivery. Journal of Colloid & Interface Science, 529, 34–43.

    CAS  Article  Google Scholar 

  24. Fasehee, H., Zarrinrad, G., Tavangar, S., Ghaffari, S., & Faghihi, S. (2016). The inhibitory effect of disulfiram encapsulated PLGA NPs on tumor growth: Different administration routes. Materials Science & Engineering: C, 63(1), 587–595.

    CAS  Article  Google Scholar 

  25. Song, W., Tang, Z., Lei, T., Wen, X., Wang, G., Zhang, D., Deng, M., Tang, X., & Chen, X. (2016). Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy. Nanomedicine, 12(2), 377–386.

    CAS  Article  Google Scholar 

  26. Graa, M., Melo-Diogo, D. D., Correia, I., & Moreira, A. (2021). Electrospun asymmetric membranes as promising wound dressings: A review. Pharmaceutics, 13(2), 183.

    Article  Google Scholar 

  27. Antunes, B., Moreira, A., Gaspar, V., & Correia, I. (2015). Chitosan/arginine-chitosan polymer blends for assembly of nanofibrous membranes for wound regeneration. Carbohydrate Polymers, 130(5), 104–112.

    CAS  Article  Google Scholar 

  28. Chanda, A., Adhikari, J., Ghosh, A., Chowdhury, S., Thomas, S., Datta, P., & Saha, P. (2018). Electrospun chitosan/polycaprolactone-hyaluronic acid bilayered scaffold for potential wound healing applications. International Journal of Biological Macromolecules, 116, 774–785.

    CAS  Article  Google Scholar 

  29. Atala, A., Lanza, R., Thomson, J., & Nerem, R. (2011). Principles of regenerative medicine. Academic Press.

    Google Scholar 

  30. Abbrent, S., Plestil, J., Hlavata, D., Lindgren, J., Tegenfeldt, J., & Wendsj. . (2001). Crystallinity and morphology of pvdf-hfp-based gel electrolytes. Polymer, 42(4), 1407–1416.

    CAS  Article  Google Scholar 

  31. Scaffaro, R., Lopresti, F., Sutera, A., Botta, L., Fontana, R. M., & Gallo, G. (2017). Plasma modified PLA electrospun membranes for actinorhodin production intensification in streptomyces coelicolor immobilized-cell cultivations. Colloids and Surfaces B: Biointerfaces, 157, 233–241.

    CAS  Article  Google Scholar 

Download references

Funding

This work was supported by the National Key R&D Program of China (No. 2017YFE0112100), EU H2020 Program (MNR4SCell No. 734174; NanoStencil No. 767285), Jilin Provincial Science and Technology Program (Nos. 20180414002GH, 20180414081GH, 20180520203JH, 20190702002GH, and 20200901011SF), Jilin Provincial DRC Research and Development Program (No. 2020C022-1), and “111” Project of China (No. D17017).

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Authors and Affiliations

  1. International Research Centre for Nano Handling and Manufacturing of China (CNM), Changchun University of Science and Technology, Changchun, 130022, China

    Chenchen Xie, Jin Yan, Siyuan Cao, Ri Liu, Baishun Sun, Ying Xie, Kaige Qu, Wenxiao Zhang, Zhankun Weng & Zuobin Wang

  2. Ministry of Education Key Laboratory for Cross-Scale Micro and Nano Manufacturing, Changchun University of Science and Technology, Changchun, 130022, China

    Chenchen Xie, Jin Yan, Siyuan Cao, Ri Liu, Baishun Sun, Ying Xie, Kaige Qu, Wenxiao Zhang, Zhankun Weng & Zuobin Wang

  3. IRAC & JR3CN, University of Bedfordshire, Luton, LU1 3JU, UK

    Zuobin Wang

Authors
  1. Chenchen Xie
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  2. Jin Yan
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  3. Siyuan Cao
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  4. Ri Liu
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  5. Baishun Sun
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  6. Ying Xie
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  7. Kaige Qu
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  8. Wenxiao Zhang
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  9. Zhankun Weng
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  10. Zuobin Wang
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Contributions

C. Xie contributed to the central idea, analyzed most of the data, and wrote the initial draft of the paper. J. Yan analyzed the XPS data. S. Cao performed the antibacterial activity experiment. R. Liu performed the surface wettability measurement. B. Sun analyzed the XRD data. Y. Xie assisted the surface wettability measurement. K. Qu provided the materials for antibacterial activity experiment. W. Zhang provided the majority of materials, reagents. Z. Weng contributed to refining the ideas and revised the manuscript. Z. Wang discussed the results and revised the manuscript.

Corresponding author

Correspondence to Zuobin Wang.

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Xie, C., Yan, J., Cao, S. et al. Bi-layered disulfiram-loaded fiber membranes with antibacterial properties for wound dressing. Appl Biochem Biotechnol 194, 1359–1372 (2022). https://doi.org/10.1007/s12010-021-03663-0

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  • DOI: https://doi.org/10.1007/s12010-021-03663-0

Keywords

  • Bi-layered disulfiram-loaded fiber membranes
  • Antibacterial activity
  • Surface wettability
  • Electrospinning
  • Wound dressing