Application of Hyperosmotic Nanoemulsions in Wound Healing: Partial Thickness Injury Model in Swine

Objective: In this work, we introduce a novel hyperosmotic nanoemulsion (HNE) topical agent for use in wound healing. These topical emulsion complexes combine a lipophilic thymol nanoemulsion with a hyperosmotic saccharide matrix. This combination has been previously shown to possess synergistic antimicrobial activity against a host of common and drug-resistant pathogens in vitro. Approach: In this study, we present additional data to assess the safety and efficacy of these emulsions in a partial thickness injury model in swine. Ten wounds sized 2 × 3.5 cm were created in 18 pigs using an electrodermatome set at a depth of 0.76 mm. The wounds were subsequently contaminated with a cocktail of Escherichia coli, Staphylococcus aureus, Enterococcus faecalis, and Candida albicans at 5 × 10⁷ total colony forming unit per wound. Treatments were subdivided in the control group and emulsion concentrations at 0.0%, 0.01%, 0.03%, and 0.063% thymol content. Longitudinal metrics for wound healing included rate of reepithelialization, wound bed color measurements, amount of wound exudate, wound swab culture data, and histological examination at 4, 7, and 14 days. The cosmetics of the healed wound were obtained at day 14 with three-dimensional photogrammetry. Results: Experimental results showed that HNE reduced the wound level bacteria count by ∼0.5-1 log versus controls after 24 h. The amount of pathogen reduction was weakly correlated to the concentration of the emulsion. In addition, all HNE groups maintained a moist wound environment and showed increased fibrin formation and improved hemostatic response. Innovation: No significant difference in the rate of reepithelialization or wound closure was found between treatment concentrations and control groups. HNE treatment did not demonstrate any adverse host tissue response. Conclusion: These results suggest HNE may be a candidate for reducing wound bacterial counts without compromising reepithelialization.