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In vitro and in vivo evaluation of a novel nitric oxide-releasing ointment for the treatment of methicillin-resistant Staphylococcus aureus-infected wounds

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Abstract

Purpose

Nitric oxide (NO) has emerged as a novel agent for the treatment of infected wounds owing to its potent wound-healing effects and antibacterial activity against drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA). In this study, we developed a NO-releasing ointment composed of S-nitrosoglutathione (GSNO) and polyethylene glycol (PEG) for the treatment of MRSA-infected cutaneous wounds.

Methods

The GSNO-incorporated PEG ointment (GPO) was successfully prepared by homogeneous dispersion of micronized GSNO in a PEG ointment base. High encapsulation efficiency was achieved (97.25%) via water-free fabrication processing of the GPO, resulting in minimal GSNO hydrolysis.

Results

When applied to a wound, the wound fluid triggered the degradation of GSNO and NO was released from the GPO for 24 h without an initial burst release. The GPO exhibited potent antibacterial effects against MRSA without cytotoxic effects against L929 cells. An in vivo wound healing experiment using a mouse MRSA-challenged full-thickness wound model revealed that the GPO could facilitate healing of infected wounds.

Conclusion

Thus, the GPO could be a promising NO-releasing formulation for the treatment of infected cutaneous wounds.

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Acknowledgements

This work was supported by a 2-year research grant from Pusan National University.

Author information

Correspondence to Jin-Wook Yoo.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Human and animal rights

All animal experiments were reviewed and approved by the Pusan National University Institutional Animal Care and Use Committee (PNU-IACUC) on 01 February 2018 (PNU-2018-1800).

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Lee, J., Hlaing, S.P., Cao, J. et al. In vitro and in vivo evaluation of a novel nitric oxide-releasing ointment for the treatment of methicillin-resistant Staphylococcus aureus-infected wounds. J. Pharm. Investig. (2020). https://doi.org/10.1007/s40005-020-00472-1

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Keywords

  • Nitric oxide
  • S-nitrosoglutathione
  • Methicillin-resistant staphylococcus aureus
  • Infected wound healing
  • Ointment