Essential Oil–Antibiotics Synergistic Delivery Strategy via Phenylboronic-Acid-Functionalized Liposomes for Targeted Treatment of MRSA Pneumonia

Methicillin-resistant Staphylococcus aureus (MRSA)-induced pneumonia has become a major global public health challenge due to its high mortality and drug resistance. Essential oils, derived from plants, offer a promising solution to combat resistance owing to their low cytotoxicity and multitarget antimicrobial properties. This study designed a phenylboronic acid (PBA)-functionalized liposomal codelivery system (P-Lip@CE) to reverse MRSA resistance by synergistically delivering cefazolin sodium (Cefas) and Alpinia zerumbet essential oil (EOFAZ). The dual-drug system exhibited good storage stability, biocompatibility, and tolerance to diverse biological environments. EOFAZ enhanced the antibacterial efficacy of Cefas by disrupting the bacterial membrane integrity and reducing its minimum inhibitory concentration (MIC) by 8-fold. P-Lip@CE showed strong bacterial adsorption due to the interaction between P-Lip and bacteria, with the in vitro MIC of P-Lip@CE being 8-fold and 33-fold lower than those of free Cefas and EOFAZ, respectively. In an MRSA-infected pneumonia model, P-Lip@CE effectively promoted tissue repair via intranasal and oral administration. This synergistic delivery strategy demonstrated a simple but effective technology for combating drug-resistant infections, allowing for reduced antibiotic dosages and the option for multiroute administration.