Terpene-Based Eutectic Solvent Microdroplets: A Strategy to Combat Antibiotic-Resistant <i>Helicobacter pylori</i>

Terpene-based therapeutic eutectic solvents (THEES) represent an innovative class of green solvents with intrinsic antimicrobial properties, offering new potential for sustainable solutions in microbial infection treatment. This study introduces the first application of THEES-based microdroplets targeting <i>Helicobacter pylori</i> (<i>H. pylori</i>), a critical global health concern due to rising antibiotic resistance. Using microfluidic technology, we developed oil-in-water (O/W) emulsion droplets from three distinct THEES systems: menthol/thymol, menthol/lidocaine, and menthol/eucalyptol. These droplets were generated via a flow-focusing glass-capillary microfluidic device, with a 10 wt % poly(vinyl alcohol) (PVA) aqueous phase and THEES as the organic phase. The presence of surfactant in the system is expected to diminish the integration of bacterial membranes and improve the antimicrobial efficiency of the emulsion droplets compared to THEES alone. Biocompatibility was first evaluated <i>via</i> metabolic activity on L929 mouse fibroblasts, followed by <i>in vitro</i> testing evaluation against both standard and antibiotic-resistant <i>H. pylori</i> strains. This novel platform THEES-based microdroplets offers a sustainable and potentially transformative strategy for addressing <i>H. pylori</i> infections, providing a breakthrough in combating antibiotic resistance and can potentially prevent the development of resistance if it is used as an alternative to antibiotics.