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Essential Oil-Antibiotics Synergistic Delivery Strategy via Phenylboronic-Acid-Functionalized Liposomes for Targeted
Qianqian Guo1,2, Zhenxia Wu1,2, Buhui Tao1,2
1The Department of Pharmaceutics of TCM (The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, the Union Key Laboratory of Guiyang City-Guizhou Medical University), School of Pharmaceutical Sciences, Guizhou Medical University, Guian New District, Guizhou 561113, China.
Abstract:
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.
Insights
A novel liposomal system combines cefazolin sodium and essential oil to combat MRSA pneumonia, reducing drug resistance and promoting tissue repair. This approach offers a promising strategy for treating antibiotic-resistant infections with lower antibiotic doses.
Area of Science:
- Pharmacology
- Nanotechnology
- Infectious Diseases
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia presents a significant global health threat due to high mortality and antimicrobial resistance.
- Essential oils show potential against resistant bacteria due to their multitarget properties and low cytotoxicity.
Purpose of the Study:
- To develop a phenylboronic acid (PBA)-functionalized liposomal codelivery system (P-Lip@CE) for synergistic delivery of cefazolin sodium (Cefas) and Alpinia zerumbet essential oil (EOFAZ).
- To investigate the potential of P-Lip@CE to reverse MRSA resistance and treat MRSA-induced pneumonia.
Main Methods:
- Fabrication of a PBA-functionalized liposomal system for codelivery of Cefas and EOFAZ.
- Evaluation of the system's stability, biocompatibility, and antibacterial efficacy in vitro.
- Assessment of P-Lip@CE in an MRSA-infected pneumonia mouse model using intranasal and oral administration.
Main Results:
- The P-Lip@CE system demonstrated good storage stability, biocompatibility, and tolerance.
- EOFAZ enhanced Cefas efficacy, reducing its minimum inhibitory concentration (MIC) by 8-fold.
- P-Lip@CE exhibited significantly lower in vitro MICs (8-fold for Cefas, 33-fold for EOFAZ) and promoted tissue repair in vivo.
Conclusions:
- The synergistic codelivery system P-Lip@CE effectively combats MRSA resistance and pneumonia.
- This strategy reduces antibiotic dosage and allows for flexible administration routes, offering a promising approach for drug-resistant infections.
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