Myrrh Oil-Based Nanoemulsion Loaded with Curcumin and Insulin: Development, Characterization, and Evaluation of Enhanced Antibacterial and Diabetic Wound-Healing Activity
Summary: Published March 16, 2026 in Pharmaceutics (MDPI), this research article from the University of Tabuk (Saudi Arabia), Qena University (Egypt), Mansoura University, Assiut University, and Badr University in Cairo describes the development, optimisation, and in vivo evaluation of a triple-agent topical wound-healing formulation: a myrrh oil-based nanoemulsion (NE) co-loaded with curcumin (CUR) in the oil phase and insulin (INS) in the aqueous phase, incorporated into a chitosan/Pluronic F-127 gel base to form a nanoemulgel designated CUR-INS-NEG. Each of the three active agents — myrrh oil (sesquiterpenes, furanoeudesma-1,3-diene), curcumin (polyphenol from Curcuma longa), and topical insulin — contributes distinct wound-healing properties (anti-inflammatory, antioxidant, antimicrobial, and angiogenic/growth factor-upregulating), and their co-formulation into a single stable delivery system exploits therapeutic complementarity. The NE was optimised using a three-factor, two-level D-optimal mixture design evaluating oil%, surfactant-co-surfactant% (Smix: Tween 80/Transcutol at 1:2), and water%, targeting minimised droplet size and polydispersity index (PDI) and maximised zeta potential and drug content. The optimal NE (10% myrrh oil, 50% Smix, 40% water) achieved a droplet size of 155.2 ± 0.8 nm, PDI of 0.28, zeta potential of −31.4 ± 0.8 mV, and drug content of 98.3 ± 0.6% — consistent with predicted values (desirability index 0.988). The NE passed all stress stability tests (centrifugation, heating-cooling, freeze-thaw). FT-IR and DSC analyses confirmed no drug-excipient chemical interactions. The final CUR-INS-NEG gel had a pH of 6.9–7.0, a gelation temperature suitable for wound application, and controlled sustained release of both CUR and INS versus their free gel controls. In antibacterial testing against five strains (S. aureus ATCC 6538, E. coli ATCC 8739, K. pneumoniae, P. aeruginosa, S. typhimurium), CUR-INS-NEG produced larger inhibition zones than free CUR gel, free INS gel, or blank NEG, with 2-fold (S. aureus) and 4-fold (E. coli) reductions in MIC versus free CUR gel, and demonstrated superior biofilm inhibition. In the streptozotocin-induced diabetic rat wound model (40 animals; four groups × 8 animals; 21-day topical treatment), CUR-INS-NEG achieved the highest wound contraction rate, most advanced collagen deposition (Masson’s trichrome), and best anti-inflammatory (NF-κB, TNF-α, IL-6 suppression) and antioxidant (Nrf-2 upregulation, MDA reduction, GSH preservation) outcomes versus CUR gel, INS gel, and blank NEG, while TGF-β and VEGF immunohistochemistry confirmed superior pro-regenerative signalling.
Key Highlights:
- Triple-agent nanoemulgel (CUR-INS-NEG): myrrh oil (anti-inflammatory, antimicrobial, analgesic), curcumin (antioxidant, anti-inflammatory, antibacterial), and topical insulin (growth factor upregulation, granulation tissue formation) co-formulated for synergistic diabetic wound healing
- Optimised nanoemulsion: 155.2 nm droplet size, PDI 0.28, zeta potential −31.4 mV, drug content 98.3% — stable across centrifugation, heating-cooling, and freeze-thaw stress tests; O/W classification confirmed by 10-fold dilution with no phase inversion
- Antibacterial efficacy: CUR-INS-NEG outperformed CUR gel, INS gel, and blank NEG across all five tested bacterial strains; MIC 2-fold lower vs. CUR gel for S. aureus and 4-fold lower for E. coli; strong biofilm inhibition (>50%) against both Gram-positive and Gram-negative strains
- In vivo wound contraction (diabetic rat model, 21 days): CUR-INS-NEG achieved highest wound closure rate; collagen deposition, VEGF expression, and TGF-β signalling all superior to individual CUR gel or INS gel groups
- Anti-inflammatory and antioxidant profile: significant suppression of NF-κB, TNF-α, and IL-6; upregulation of Nrf-2; reduction in MDA; preservation of GSH — addressing the chronic oxidative-inflammatory wound environment characteristic of diabetes
- Formulation advantages: nanoscale droplets enhance skin penetration to wound bed; chitosan/Pluronic F-127 gel provides extended residence time, thermoresponsive gelation at body temperature, and bioadhesion — improving patient compliance for topical wound application
Keywords: nanoemulsion diabetic wound healing, curcumin wound care, topical insulin wound healing, myrrh oil wound healing, nanoemulgel antibacterial wound, diabetic wound anti-inflammatory antioxidant
Ayman Salama, Mona Qushawy, Ghareb M. Soliman