Enhancement of tobramycin and amikacin activities by co-encapsulation in liposomal-thymoquinone formulation: antibacterial, antibiofilm, and cytocompatibility study

Background and aim Aminoglycoside antibiotics (AGAs) are vital but are faced with limited uptake, resistance, and nephrotoxicity. Thymoquinone (THQ) from Nigella sativa has antibacterial and cytoprotective effects but is unstable, posing challenges for formulation. This study co-encapsulated amikacin (AMK) and tobramycin (TOB) with THQ in liposomes to improve antimicrobial activity and renal cytocompatibility.Methods Liposomes (Lipo-AMK-THQ and Lipo-TOB-THQ) were prepared and characterized using dynamic light scattering, zeta potential, encapsulation efficiency, Fourier transform infrared spectroscopy, and transmission electron microscopy. Antimicrobial efficacy was evaluated using minimum inhibitory or bactericidal concentrations (MIC-MBC), time-kill, and biofilm inhibition assays. Cytocompatibility was assessed in HK-2 and HEK293T cells.Results Formulations exhibited nanoscale size (around 100 nm), low polydispersity (0.1–0.2), and zeta potential around −60 mV. Sustained antibiotic release over 24 h was observed. MIC values were reduced compared to free antibiotics, particularly against resistant MRSA and E. coli isolates (by up to 31–500-fold). Enhanced biofilm inhibition was observed (up to 90–98%) relative to free drugs (38–41%). Cell viability remained at 63–100% (HK-2) and 84–100% (HEK293T).Conclusion Co-encapsulation of selected AGAs with THQ in liposomes improved antibacterial and antibiofilm activity while maintaining cytocompatibility, supporting further in vivo evaluation to establish the therapeutic potential and safety.