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Nitric oxide-releasing albumin nanoclusters facilitate healing of methicillin-resistant Staphylococcus aureus-infected cutaneous wounds

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Abstract

Purpose

Although nitric oxide (NO)-releasing nanoparticles have garnered significant attention owing to their potent antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA) and direct promotion of wound healing, the majority of NO-releasing nanoparticles are composed of synthetic polymers or inorganic materials, which may lead to unfavorable effects in the body. To overcome this limitation, we developed NO-releasing albumin nanoclusters (NO/ANCs) using bovine serum albumin, a fully biocompatible endogenous material.

Methods

NO/ANCs were fabricated by incorporating diethylenetriamine diazeniumdiolate (DT/NO) into albumin nanoclusters via electrostatic interactions, followed by glutaraldehyde crosslinking between the albumin molecules. The antibacterial effects of the NO/ANCs were investigated using the LIVE/DEAD® BacLight™ bacterial viability kit. The enhanced wound healing and in vivo antibacterial effects were evaluated in a mouse model of MRSA-challenged full-thickness wounds.

Results

NO/ANCs were successfully fabricated and could release NO for more than 17 h. NO/ANCs demonstrated enhanced in vitro antibacterial effects and exhibited improved in vivo antibacterial and wound-healing effects in a mouse model of MRSA-challenged full-thickness wounds.

Conclusion

NO/ANCs could be a promising formulation for the treatment of MRSA-infected cutaneous wounds.

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Acknowledgements

This research was supported by PNU-RENovation (2022–2023).

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Author notes

  1. Dongmin Kwak and Juho Lee have contributed equally to this work.

Authors and Affiliations

  1. College of Pharmacy, Pusan National University, Busan, 609- 735, Republic of Korea

    Dongmin Kwak, Juho Lee, Jihyun Kim, Hyunwoo Kim & Jin-Wook Yoo

  2. Research Institute for Drug Development, Pusan National University, Busan, 46241, Republic of Korea

    Juho Lee, Jihyun Kim & Jin-Wook Yoo

  3. College of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea

    Jae-Young Lee

  4. College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 08826, Republic of Korea

    Dae-Duk Kim

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  1. Dongmin Kwak
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Correspondence to Jin-Wook Yoo.

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All authors (D. Kwak, J. Lee, J. Kim, H. Kim, J.-Y. Lee, D.‑D. Kim, and J.‑W. Yoo)

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All animal experiments were reviewed and approved by the Pusan National University Institutional Animal Care and Use Committee (PNU-IACUC) on May 16, 2022 (PNU-2022-0090).

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Kwak, D., Lee, J., Kim, J. et al. Nitric oxide-releasing albumin nanoclusters facilitate healing of methicillin-resistant Staphylococcus aureus-infected cutaneous wounds. J. Pharm. Investig. 54, 51–60 (2024). https://doi.org/10.1007/s40005-023-00641-y

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