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

IF 3.8 2区医学 Q2 CHEMISTRY, MEDICINAL

ACS Infectious Diseases Pub Date : 2025-09-03 DOI:10.1021/acsinfecdis.5c00438

Qianqian Guo*, Zhenxia Wu, Buhui Tao, Ling Tao, Qian Wang, Chao Huang, Yang Gao, Yu-e Wang, Xingjie Wu, Ying Chen, Ting Guo* and Xiangchun Shen*,

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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.

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苯硼酸功能化脂质体精油-抗生素协同递送策略靶向治疗MRSA肺炎。

耐甲氧西林金黄色葡萄球菌（MRSA）引起的肺炎由于其高死亡率和耐药性已成为一个主要的全球公共卫生挑战。从植物中提取的精油，由于其低细胞毒性和多靶点抗菌特性，为对抗耐药性提供了一个很有前途的解决方案。本研究设计了一种苯硼酸（PBA）功能化的脂质体共递送系统（P-Lip@CE），通过协同递送头孢唑啉钠（Cefas）和茜草精油（EOFAZ）来逆转MRSA耐药性。该双药体系具有良好的储存稳定性、生物相容性和对多种生物环境的耐受性。EOFAZ通过破坏细菌膜的完整性，使其最低抑菌浓度（MIC）降低8倍，增强了Cefas的抑菌效果。由于P-Lip与细菌的相互作用，P-Lip@CE表现出较强的细菌吸附能力，P-Lip@CE的体外MIC分别比游离Cefas和EOFAZ低8倍和33倍。在mrsa感染的肺炎模型中，P-Lip@CE通过鼻内和口服给药有效地促进组织修复。这种协同给药策略证明了一种抗击耐药感染的简单而有效的技术，允许减少抗生素剂量和选择多途径给药。

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来源期刊

ACS Infectious Diseases CHEMISTRY, MEDICINALINFECTIOUS DISEASES&nb-INFECTIOUS DISEASES

CiteScore

9.70

自引率

3.80%

发文量

213

期刊介绍： ACS Infectious Diseases will be the first journal to highlight chemistry and its role in this multidisciplinary and collaborative research area. The journal will cover a diverse array of topics including, but not limited to: * Discovery and development of new antimicrobial agents — identified through target- or phenotypic-based approaches as well as compounds that induce synergy with antimicrobials. * Characterization and validation of drug target or pathways — use of single target and genome-wide knockdown and knockouts, biochemical studies, structural biology, new technologies to facilitate characterization and prioritization of potential drug targets. * Mechanism of drug resistance — fundamental research that advances our understanding of resistance; strategies to prevent resistance. * Mechanisms of action — use of genetic, metabolomic, and activity- and affinity-based protein profiling to elucidate the mechanism of action of clinical and experimental antimicrobial agents. * Host-pathogen interactions — tools for studying host-pathogen interactions, cellular biochemistry of hosts and pathogens, and molecular interactions of pathogens with host microbiota. * Small molecule vaccine adjuvants for infectious disease. * Viral and bacterial biochemistry and molecular biology.