Preparation, Characterization, and Antibacterial Activity of Geraniol and Citral Co-Encapsulated Liposomes: In Vitro...

The global overuse of antibiotics has accelerated multidrug resistance in Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), which is challenging to treat clinically. Geraniol and citral have therapeutic potential but are limited by poor solubility, stability, and bioavailability. This study co-encapsulated them in liposomes (G/C liposomes) via ethanol injection, which was optimized via single-factor experiments and response surface methodology. The optimized G/C liposomes had good stability, high encapsulation efficiencies (geraniol, 91.74%; citral, 89.42%), 107.90 nm particle size, 0.18 PDI, and -4.37 mV zeta potential. In vitro, G/C liposomes displayed stronger anti-MRSA activity than free G/C, with dose-dependent inhibition of bacterial growth and biofilm formation. In vivo, 0.24 g/kg G/C liposomes achieved 100% survival in infected mice, with an ED₅₀ of 0.085 g/kg, which was lower than that of 0.12 g/kg free G/C. They also reduced IL-6, IL-1β, and TNF-α levels and mitigated pathological damage to major organs. Thus, G/C liposomes enhance the solubility and stability of geraniol and citral while increasing their antibacterial activity both in vitro and in vivo.