Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) remains a challenging issue in the treatment of diabetic wounds. The current researchinvestigates the formulation, antimicrobial, and wound healing efficacy of D-carvone-based nanoemulgel against clinical MRSA strains collected from diabetic wound infections. Nanoemulsion and nanoemulgel preparations for carvone were prepared and assessed. The antibacterial activity was assessed using both the cup method and microtiter assay, in addition to electron microscopy and molecular techniques. An excision wound model was used to evaluate the diabetic wound healing activity of NPs carvone. Diabetic rats, induced via streptozotocin (STZ, 65 mg/kg, i.p.), were separated into three groups: diabetic negative control, carvone, and NPs carvone groups, in which diabetic rats were allowed to heal spontaneously or treated by applying carvone alone or NPs carvone ointment, respectively. NPs D-carvone nanoemulgel demonstrated favorable characteristics suggesting enhanced tissue penetration; therefore, it was selected for further assessment. The antibacterial activity of D-carvone oil exhibited weak activity against all MRSA strains except for the AH-7 strain. On the other hand, both nanoemulsion and nanoemulgel formulations showed improved antibacterial effects, with the highest effect detected in strain AS-8 and the lowest in NCI-5, with MIC values ≤ 0.25 µg/ml for all strains. SEM images showed morphological changes in MRSA strains after treatment with NPs carvone. NPs carvone exhibited higher wound contraction %, faster epithelialization, and instigated collagen deposition, demonstrating enhanced healing processes. Additionally, NPs carvone intensified angiogenesis-related factors and antioxidant enzymes and reduced lipid peroxidation and inflammatory mediators. D-carvone nanoemulgel formulations exhibit effective antimicrobial activity against MRSA strains derived from diabetic wound infections. KEY POINTS: • D-carvone NP formulations exhibit effective antimicrobial activity against MRSA. • Nanoencapsulation improved efficacy and stability of D-carvone. • D-carvone nanoemulgels demonstrated superior diabetic wounds healing ability.