Linking chemical-composition to antimicrobial efficacy: development of an essential oil-based topical gel prototype

Antimicrobial resistance (AMR) is problematic for the management of chronic wound infection, where biofilms confer increased tolerance to treatments. A wealth of research describes the antimicrobial activity of essential oils, but none have been formulated for clinical use. We screened ten commercially available essential oils from the Lamiaceae plant family (thyme, rosemary, basil, oregano, clary sage) for bacteriostatic, bactericidal, and anti-biofilm activity. TD-GCMS was used to identify highly abundant compounds which were mapped to efficacy data. Thyme essential oils were antimicrobial against both Pseudomonas aeruginosa and Staphylococcus aureus and had the most potent anti-biofilm activity. Three compounds were common and highly abundant in these oils: o-cymene, 2-isopropyl-4-methyl-phenol (o-thymol/carvacrol), and thymol. The most efficacious red and white thyme oils were formulated into Laponite-based hydrogel emulsions capable of inhibiting both P. aeruginosa and S. aureus in static and dynamic biofilm models. Notably, the efficacy of both gels diverged from that predicted by MIC, MBC, and MBIC values, highlighting the limitations of reductionist analyses in predicting real-world antimicrobial performance. Key points: • Thyme oils are the most efficacious of the Lamiaceae plant oils tested • Thymol isomers and o-cymene are abundant in thyme oils, but minor components also play a role in antimicrobial activity • Hydrogel efficacy arises from interactions between formulation and wound microenvironment