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ORIGINAL RESEARCH
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Topical triple-strategy nanoemulsion formulations of cetrimide for treating methicillin-resistant Staphylococcus aureus-infected skin wounds

Rawia Khalil1 ,  Mohamed F. AbdelHameed2 ,  Shaymaa A. Ismail3 ,  Amira A. Hassan3 ,  Marwa E. Shabana4 ,  Wenli Zhang5 ,  Eman S. Shalaby1*
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1 Department of Pharmaceutical Technology, Pharmaceutical and Drug Research Institute, National Research Centre, Giza, Egypt
2 Department of Pharmacology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
3 Department of Chemistry of Natural and Microbial Products, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Giza, Egypt
4 Department of Pathology, Medical Research and Clinical Studies Institute, National Research Centre, Giza, Egypt
5 Department of Pharmaceutics, School of Pharmacy Pharmaceutical University, Nanjing, Jiangsu, China
BMT, 00039 https://doi.org/10.12336/bmt.25.00039
Submitted: 21 May 2025 | Revised: 20 July 2025 | Accepted: 21 July 2025 | Published: 21 August 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Wound management remains a global health concern due to its fatal complications, and cetrimide (CET) is an antimicrobial quaternary ammonium chemical used in wound healing. This study aimed to develop and assess the therapeutic potential of a CET-loaded nanoemulsion for treating methicillin-resistant Staphylococcus aureus-infected wounds. A high-speed homogenization method was used for preparing nanoemulsions containing CET, sesame oil, and linalool. Entrapment efficiency, droplet size, and zeta potential were evaluated to identify the optimal formulations. Further characterization included in vitro release studies, differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FTIR), and transmission electron microscopy. The selected formulations were subsequently evaluated for their in vivo wound healing efficacy in a full-thickness wound model. The formulated nanoemulsion demonstrated high entrapment efficiency (92.71– 98.57%), with droplet sizes of 150–399 nm and zeta potential of +10–+27.9 mV, suggesting favorable physical stability. The in vitro drug release followed a biphasic pattern. DSC peaks of the drug were diffused in the formulation, suggesting its presence in the amorphous form. FTIR study showed no new peaks, suggesting no chemical interaction between the drug and the formulation components. In vivo evaluation of wound healing efficacy revealed a marked reduction in wound size following treatment with selected CET-loaded nanoemulsions. In addition, a significant decrease in tumor necrosis factor-alpha levels, alongside increased expression of B-cell lymphoma 2 and collagen type I, was observed in treated rats. Histological analysis further supported these findings, revealing near-normal tissue architecture. Collectively, these results indicate that CET-loaded nanoemulsions represent a promising approach for enhancing topical wound healing outcomes.

Keywords
Nanoemulsion
Cetrimide
Wound healing
Methicillin-resistant Staphylococcus aureus
Histopathology
Funding
None.
Conflict of interest
The authors have no financial or personal interests that could be perceived as influencing the content of this work.
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