Skip to main content
SpringerLink
Log in

Physical-Chemical Characterizations of Synthetic Dual Niosomes for Antibacterial Delivery of Lysostaphin and LL-37

  • Published:
Pharmaceutical Chemistry Journal Aims and scope

Non-ionic surfactant vesicles known as niosomes are synthetic vesicles with numerous pharmaceutical applications. In this study, a unique combination of two antibacterial macromolecules, lysostaphin protein and LL-37 peptide, was prepared in a nanoniosomal delivery system to evaluate the physicochemical properties of prepared niosomes and the possible synergistic interactions of niosomal drugs. Two different niosomal formulations of lysostaphin and LL-37 were prepared using a thin film hydration method and analyzed in terms of size, shape, entrapment efficiency, and FTIR spectroscopy. The stability of niosomes was evaluated at 4, 25, and 37°C. Also, the antibacterial activity of LL-37 as a single drug or in combination with lysostaphin was evaluated in free and encapsulated forms against E. coli and A. baumannii for 72 h using time kill assay. The optimal niosomal formulation was obtained by mixing surfactants (Span 60 and Tween 60; 2:1 w/w) and cholesterol at a ratio of 1:1 (w/w). Mean diameters of lysostaphin and LL-37 in optimal formulation were 508.50 and 292.65 nm respectively. This formulation showed spherical well-dispersed niosomes with high entrapment efficiency and had good stability at 4°C for 2 months. Furthermore, no chemical bond was formed between the niosomal membrane and lysostaphin or LL-37, according to FTIR analysis. Finally, a prolonged antibacterial activity of dual-drug-loaded niosomes was observed compared with their free form. The finding indicated that lysostaphin/LL-37 in a niosomal nanocarrier offers a delivery system with promising physicochemical properties for long-term protection against human chronic infections caused by Gram-negative bacteria.

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.

Similar content being viewed by others

References

  1. F. Heidari, I. Akbarzadeh, D. Nourouzian, et al., Adv. Powder Technol., 31, 4768 – 4781(2022).

    Article  Google Scholar 

  2. I. Akbarzadeh, M. Keramati, A. Azadi, et al., Chem. Phys. Lipids, 234, 105019 (2021).

    Article  CAS  PubMed  Google Scholar 

  3. M. Fumakia and E. A. Ho, Mol. Pharm., 13, 2318 – 2331 (2016).

    Article  CAS  PubMed  Google Scholar 

  4. K. Moribe and K. Maruyama, Curr. Pharm. Des., 8, 441 – 454 (2002).

    Article  CAS  PubMed  Google Scholar 

  5. R. Cortesi, E. Esposito, F. Corradini, et al., Int. J. Pharm, 339, 52 – 60 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. S. Xia and S. Xu, Food Res. Int., 38, 289 – 296 (2005).

    Article  CAS  Google Scholar 

  7. I. Akbarzadeh, A. Saremi Poor, S. Yaghmaei, et al., Drug Dev Ind Pharm, 46, 1535 – 1549 (2020)

  8. A. A. Targhi, A. Moammeri, E. Jamshidifar, et al., Bioorg. Chem., 115, 105116 (2021).

    Article  CAS  PubMed  Google Scholar 

  9. S. Maria-Neto, K. C. de Almeida, M. L. R. Macedo and O. L. Franco, Biochim. Biophys. Acta, 1848, 3078 – 3088 (2015).

    Article  CAS  PubMed  Google Scholar 

  10. J. Z. Kubicek-Sutherland, H. Lofton, M. Vestergaard, et al., J. Antimicrob. Chemother., 72, 115 – 127 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  11. M. Magana, M. Pushpanathan, A. L. Santos, et al., Lancet Infect. Dis., 20(9), e216 (2020).

    Article  CAS  PubMed  Google Scholar 

  12. L. Steinstraesser, T. Koehler, F. Jacobsen, et al., Mol. Med., 14, 528 – 537 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. A. J. Duplantier and M. L. van Hoek, Front. Immunol., 4, 143 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  14. E. Phillips and T. Young, Br. J. Nurs, 4, 1345 – 1349 (1995).

    Article  CAS  PubMed  Google Scholar 

  15. S. F. van Vuuren, M. N. Nkwanyana and H. deWet, BMC Complement. Altern. Med., 15, 1 – 8 (2015).

  16. P. Mitkowski, E. Jagielska, E. Nowak, et al., Sci. Rep., 9, 1 – 14 (2019).

    Article  CAS  Google Scholar 

  17. A. P. Desbois and P. J. Coote, Eur. J. Clin. Microbiol. Infect. Dis., 30, 1015 – 1021 (2011).

    Article  CAS  PubMed  Google Scholar 

  18. S. Graham and P. J. Coote, J. Antimicrob. Chemother., 59, 759 – 762 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. M. S. Zharkova, D. S. Orlov, O. Y. Golubeva, et al., Front. Cell Infect. Microbiol., 9, 128 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. S. Sadeghi, H. Bakhshandeh, R. A. Cohan, et al., Int. J. Nanomedicine, 14, 9777 – 9792 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. N. J. Kruger, The protein protocols handbook, Springer (2009), pp. 17 – 24.

  22. J. Satish, A. S. Amusa and P. Gopalakrishna, J. Pharm. Technol. Drug Res., 1, 1 – 11 (2012).

    Article  CAS  Google Scholar 

  23. P. Balakrishnan, S. Shanmugam,W. S. Lee, et al., Int. J. Pharm., 377, 1 – 8 (2009).

    Article  CAS  PubMed  Google Scholar 

  24. M. Hedayati Ch, A. Abolhassani Targhi, F. Shamsi, et al., J. Biomed. Mater. Res. A, 109, 966 – 980 (2021).

  25. T. Yoshioka, B. Sternberg and A. T. Florence, Int. J. Pharm., 105, 1 – 6 (1994).

    Article  CAS  Google Scholar 

  26. V. B. Junyaprasert, P. Singhsa, J. Suksiriworapong, et al., Int. J. Pharm., 423, 303 – 311 (2012).

    Article  CAS  PubMed  Google Scholar 

  27. R. Rochdy Haj-Ahmad, A. Ali Elkordy and C. Shu Chaw, Curr. Drug Deliv., 12, 628 – 639 (2015).

  28. G. Arzani, A. Haeri, M. Daeihamed, et al., Int. J. Nanomedicine, 10, 4797 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. H. Abdelkader, S. Ismail, A. Kamal, et al., J. Pharm. Sci., 100, 1833 – 1846 (2011).

    Article  CAS  PubMed  Google Scholar 

  30. A. Manosroi, P. Wongtrakul, J. Manosroi, et al., Colloids Surf. B. Biointerfaces, 30, 129 – 138 (2003).

    Article  CAS  Google Scholar 

  31. M. Mokhtar, O. A. Sammour, M. A. Hammad, et al., Int. J. Pharm., 361, 104 – 111 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. X. F. Li, G. Y. Zhang, J. F. Dong, et al., Chin. J. Chem., 24, 311 – 315 (2006).

    Article  CAS  Google Scholar 

  33. J.-C. Colas, W. Shi, V. M. Rao, et al., Micron, 38, 841 – 847 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. N. M. Zuki, N. Ismail and F. M. Omar, Int. J. Environmental Engineering, 10(1), 33–46 (2019).

    Article  Google Scholar 

  35. I. F. Uchegbu and A. T. Florence, Adv. Colloid Interface Sci., 58, 1 – 55 (1995).

    Article  CAS  Google Scholar 

  36. M. Lawrence, S. Chauhan, S. Lawrence, et al., STP Pharma Sci., 6, 49 – 60 (1996).

    Google Scholar 

  37. M. Seras-Cansell, M. Ollivon and S. Lesieur, STP Pharma Sci., 6, 12 – 20 (1996).

    Google Scholar 

  38. H. Hofland, J. Bouwstra, J. Verhoef, et al., J. Pharm. Pharmacol., 44, 287 – 294 (1992).

    Article  CAS  PubMed  Google Scholar 

  39. V. Akbari, D. Abedi, A. Pardakhty, et al., Avicenna J. Med. Biotechnol., 7, 69 (2015).

    Google Scholar 

  40. S. Sohrabi, A. Haeri, A. Mahboubi, et al., Int. J. Biol. Macromol., 85, 625 – 633 (2016).

    Article  CAS  PubMed  Google Scholar 

  41. X. Chen, F. Niyonsaba, H. Ushio, et al., J. Dermatol. Sci., 40, 123 – 132 (2005).

    Article  CAS  PubMed  Google Scholar 

  42. E. M. Haisma, A. de Breij, H. Chan, et al., Antimicrob. Agents Chemother., 58, 4411 – 4419 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  43. K. Leszczyñska, D. Namiot, F. J. Byfield, et al., J. Antimicrob. Chemother., 68, 610 – 618 (2013).

    Article  PubMed  Google Scholar 

  44. B. C. Koppen, P. P. Mulder, L. de Boer, et al., Int. J. Antimicrob. Agents, 53, 143 – 151 (2019).

    Article  CAS  PubMed  Google Scholar 

  45. E. Sugawara and H. Nikaido, J. Bacteriol., 194, 4089 – 4096 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. E. M. Nestorovich, E. Sugawara, H. Nikaido, et al., Biol. Chem., 281, 16230 – 16237 (2006).

    Article  CAS  Google Scholar 

  47. E. Sugawara, K. Nagano and H. Nikaido, MBio, 1, e00228 – 00210 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  48. M. Zahn, S. P. Bhamidimarri, A. Baslé, et al., Structure, 24, 221 – 231 (2016).

    Article  CAS  PubMed  Google Scholar 

  49. J. Vergalli, I. V. Bodrenko, M. Masi, et al., Nat. Rev. Microbiol., 18, 164 – 176 (2020).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nano biotechnology, New Technology Research Group, Pasteur Institute of Iran, Tehran, Iran

    Somayeh Sadeghi, Haleh Bakhshandeh, Reza Ahangari Cohan & Dariush Norouzian

  2. Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran

    Somayeh Sadeghi & Parastoo Ehsani

Authors
  1. Somayeh Sadeghi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Haleh Bakhshandeh
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Reza Ahangari Cohan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Parastoo Ehsani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Dariush Norouzian
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Haleh Bakhshandeh.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sadeghi, S., Bakhshandeh, H., Cohan, R.A. et al. Physical-Chemical Characterizations of Synthetic Dual Niosomes for Antibacterial Delivery of Lysostaphin and LL-37. Pharm Chem J 57, 1418–1427 (2023). https://doi.org/10.1007/s11094-023-03005-w

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11094-023-03005-w

Keywords

Search

Navigation