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Peer-reviewedCC BYPharmaceutics

Antibacterial, Anti-Inflammatory, and Wound-Healing Effects of Micromeria fruticosa Essential Oil-Loaded Nanoemulsion in MRSA-Infected Diabetic Wounds: In Vitro and In Vivo Evaluation.

10 affiliations
  1. 1Department of Medical Pharmacology, Faculty of Medicine, Kafkas University, Kars 36100, Türkiye.
  2. 2Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Harran University, Sanliurfa 63300, Türkiye.
  3. 3Department of Pharmacology, Faculty of Pharmacy, Harran University, Sanliurfa 63300, Türkiye.
  4. 4Department of Pharmaceutical Botany, Faculty of Pharmacy, Çukurova University, Adana 01330, Türkiye.
  5. 5Department of Pharmaceutical Technology, Faculty of Pharmacy, Çukurova University, Adana 01330, Türkiye.
  6. 6Department of Pharmaceutical Technology, Faculty of Pharmacy, Bahçeşehir University, Istanbul 34353, Türkiye.
  7. 7Department of Pharmaceutical Technology, Faculty of Pharmacy, Anadolu University, Eskisehir 26470, Türkiye.
  8. 8Department of Pathology, Faculty of Veterinary Medicine, Harran University, Sanliurfa 63000, Türkiye.
  9. 9Department of Genetics, Faculty of Veterinary Medicine, Harran University, Sanliurfa 63200, Türkiye.
  10. 10Department of Biochemistry, Faculty of Pharmacy, Çukurova University, Adana 01330, Türkiye.

Abstract

Background/Objectives: Diabetic foot ulcers infected with methicillin-resistant Staphylococcus aureus (MRSA) heal poorly and respond inadequately to conventional antibiotic therapy. This study developed a Micromeria fruticosa essential oil-loaded nanoemulsion (Mf-NE) as a topical treatment for such wounds. Methods: The essential oil was obtained by hydrodistillation and analyzed by GC-MS. Nanoemulsions were developed from pseudoternary phase diagrams using oleic acid and a Cremophor® EL/Tween 80-Transcutol® system (2:1 surfactant/cosurfactant) and characterized physicochemically. Antibacterial activity against MRSA (ATCC 43300) was assessed by agar well diffusion and microdilution, antioxidant activity by DPPH and ABTS assays, and cytocompatibility by MTT assay on L929 fibroblasts. Efficacy was evaluated over 12 days in a streptozotocin-induced MRSA-infected diabetic wound model in rats. Results: Pulegone (42.81%) and piperitenone (29.73%) were the major constituents. Incorporation of 5% (w/w) essential oil raised the droplet size from 214.5 ± 14.4 to 292.9 ± 9.9 nm; both formulations had a dermatologically acceptable pH and Newtonian flow behavior. Mf-NE produced a 16.1 mm inhibition zone and a MIC of 1.25 mg/mL, whereas NE produced no inhibition zone and had a MIC of 5 mg/mL. Radical scavenging reached 61.5% by DPPH at 10 mg/mL and 71.5% by ABTS at 0.2 mg/mL, and cell viability remained above 87%. The NE and Mf-NE formulations also demonstrated good biocompatibility in L929 fibroblast cells. Topical Mf-NE reduced the remaining wound area to 4.8 ± 0.9% of the initial area by day 12, compared with 21.0 ± 1.9% for Fucidin, 26.1 ± 1.9% for NE and 57.2 ± 1.3% for the untreated group; bacterial colonization was almost completely suppressed, TNF-α and IL-1β expression was significantly decreased, and composite histopathological scores were lower than in the untreated group (p = 0.0007). Conclusions: Mf-NE is a promising topical candidate for MRSA-infected diabetic wounds. Formulation-specific dermal and systemic safety requires further evaluation.

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BibTeX
@article{mammadov2026antibacterial,
  title = {{Antibacterial, Anti-Inflammatory, and Wound-Healing Effects of Micromeria fruticosa Essential Oil-Loaded Nanoemulsion in MRSA-Infected Diabetic Wounds: In Vitro and In Vivo Evaluation.}},
  author = {Azad Mammadov and Mehmet Çimentepe and Özge Öztürk Çimentepe and Serpil Demirci Kayiran and Umay Merve Güven Bolgen and Tilbe Çevikelli and Ahmet Alper Öztürk and Muhammet Bahaeddin Dörtbudak and Akın Yiğin and Metin Yildirim},
  journal = {Pharmaceutics},
  year = {2026},
  month = oct,
  doi = {10.3390/pharmaceutics18101252},
  url = {https://europepmc.org/article/MED/42942784},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Antibacterial, Anti-Inflammatory, and Wound-Healing Effects of Micromeria fruticosa Essential Oil-Loaded Nanoemulsion in MRSA-Infected Diabetic Wounds: In Vitro and In Vivo Evaluation.
AU  - Azad Mammadov
AU  - Mehmet Çimentepe
AU  - Özge Öztürk Çimentepe
AU  - Serpil Demirci Kayiran
AU  - Umay Merve Güven Bolgen
AU  - Tilbe Çevikelli
AU  - Ahmet Alper Öztürk
AU  - Muhammet Bahaeddin Dörtbudak
AU  - Akın Yiğin
AU  - Metin Yildirim
PY  - 2026
DA  - 2026/10/01
JO  - Pharmaceutics
DO  - 10.3390/pharmaceutics18101252
UR  - https://europepmc.org/article/MED/42942784
AB  - Background/Objectives: Diabetic foot ulcers infected with methicillin-resistant Staphylococcus aureus (MRSA) heal poorly and respond inadequately to conventional antibiotic therapy. This study developed a Micromeria fruticosa essential oil-loaded nanoemulsion (Mf-NE) as a topical treatment for such wounds. Methods: The essential oil was obtained by hydrodistillation and analyzed by GC-MS. Nanoemulsions were developed from pseudoternary phase diagrams using oleic acid and a Cremophor® EL/Tween 80-Transcutol® system (2:1 surfactant/cosurfactant) and characterized physicochemically. Antibacterial activity against MRSA (ATCC 43300) was assessed by agar well diffusion and microdilution, antioxidant activity by DPPH and ABTS assays, and cytocompatibility by MTT assay on L929 fibroblasts. Efficacy was evaluated over 12 days in a streptozotocin-induced MRSA-infected diabetic wound model in rats. Results: Pulegone (42.81%) and piperitenone (29.73%) were the major constituents. Incorporation of 5% (w/w) essential oil raised the droplet size from 214.5 ± 14.4 to 292.9 ± 9.9 nm; both formulations had a dermatologically acceptable pH and Newtonian flow behavior. Mf-NE produced a 16.1 mm inhibition zone and a MIC of 1.25 mg/mL, whereas NE produced no inhibition zone and had a MIC of 5 mg/mL. Radical scavenging reached 61.5% by DPPH at 10 mg/mL and 71.5% by ABTS at 0.2 mg/mL, and cell viability remained above 87%. The NE and Mf-NE formulations also demonstrated good biocompatibility in L929 fibroblast cells. Topical Mf-NE reduced the remaining wound area to 4.8 ± 0.9% of the initial area by day 12, compared with 21.0 ± 1.9% for Fucidin, 26.1 ± 1.9% for NE and 57.2 ± 1.3% for the untreated group; bacterial colonization was almost completely suppressed, TNF-α and IL-1β expression was significantly decreased, and composite histopathological scores were lower than in the untreated group (p = 0.0007). Conclusions: Mf-NE is a promising topical candidate for MRSA-infected diabetic wounds. Formulation-specific dermal and systemic safety requires further evaluation.
SN  - 1999-4923
ER  -