Dogheim Gaidaa M, Shehat Michael G, Mahdy Dina M, Barakat Hebatallah S, Abouelfetouh Alaa, Ramadan Alyaa A
Pharmaceutics department, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
Sci Rep. 2025 Apr 26;15(1):14677. doi: 10.1038/s41598-025-95343-w.
Methicillin-resistant Staphylococcus aureus (MRSA) is challenging modern antimicrobial therapy due to its high antimicrobial resistance. Nutraceuticals have gained a lot of interest and their incorporation into nanoparticles further improves their efficacy. This study aimed to evaluate the antibacterial activity of linalool-based lipid nanocapsules loaded with resveratrol (LIN-LNC-RES) as a synergistic strategy against MRSA. LIN-LNC-RES were prepared by the phase inversion temperature method and characterized for their colloidal properties, in vitro release, and stability. The antibacterial and antibiofilm activity against S. aureus and different MRSA clinical isolates were investigated. Furthermore, scanning electron microscopy (SEM) imaging for visualization of biofilm formation and bacterial membrane integrity as well as mechanistic investigation using quantitative real-time polymerase chain reaction (qRT-PCR) analysis were performed. LIN-LNCs-RES demonstrated favorable properties with a size of 35.19 ± 0.72 nm, PDI of 0.09 ± 0.02 and a zeta potential of -2.53 ± 0.07 mV with RES 98% EE. They showed a controlled release of RES over 24 h and were stable at 4 °C for 3 months. Compared to free drug, LIN-LNC-RES showed a 4-fold decrease in MIC values and 10-fold decrease in half maximal biofilm inhibitory concentration value. Biofilm eradication assay showed superiority of LIN-LNC-RES over RES against all isolates with disrupted bacterial membranes as revealed by SEM. Mechanistically, qRT-PCR showed that LIN-LNC-RES significantly reduced RNAIII gene expression as well as the expression of SaeRS two component system, potentially affecting quorum sensing and virulence factors expression. RES-loaded LIN-based nanosystem offers a great potential for combating MRSA infections, neutralizing its virulence activity hence, overcoming antimicrobial resistance.
耐甲氧西林金黄色葡萄球菌（MRSA）因其高度的抗菌耐药性，对现代抗菌治疗构成了挑战。营养保健品已引起广泛关注，将其纳入纳米颗粒可进一步提高其疗效。本研究旨在评估负载白藜芦醇的芳樟醇基脂质纳米胶囊（LIN-LNC-RES）作为对抗MRSA的协同策略的抗菌活性。通过相转变温度法制备LIN-LNC-RES，并对其胶体性质、体外释放和稳定性进行表征。研究了其对金黄色葡萄球菌和不同MRSA临床分离株的抗菌和抗生物膜活性。此外，还进行了扫描电子显微镜（SEM）成像以观察生物膜形成和细菌膜完整性，以及使用定量实时聚合酶链反应（qRT-PCR）分析进行机制研究。LIN-LNCs-RES表现出良好的性质，粒径为35.19±0.72nm，多分散指数（PDI）为0.09±0.02，ζ电位为-2.53±0.07mV，白藜芦醇包封率为98%。它们显示白藜芦醇在24小时内可控释放，并在4℃下稳定3个月。与游离药物相比，LIN-LNC-RES的最低抑菌浓度（MIC）值降低了4倍，半数最大生物膜抑制浓度值降低了10倍。生物膜根除试验表明，LIN-LNC-RES相对于白藜芦醇对所有分离株具有优势，SEM显示细菌膜被破坏。从机制上讲，qRT-PCR表明LIN-LNC-RES显著降低了RNAIII基因表达以及双组分系统SaeRS的表达，可能影响群体感应和毒力因子表达。负载白藜芦醇的LIN基纳米系统在对抗MRSA感染、中和其毒力活性从而克服抗菌耐药性方面具有巨大潜力。
