Anti-Biofilm Effect of Ampicillin-Loaded Poly (Lactic-co-glycolic Acid) Nanoparticles Conjugated with Lysostaphin on Methicillin-Resistant Staphylococcus aureus

Elahe Norouzi, Seyed Mostafa Hosseini, Babak Asghari, Reza Mahjoub, Ehsan Nazarzadeh Zare, Mohammad-Ali Shahbazi, Fereshte Kalhori, Mohammad Reza Arabestani
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Abstract

Staphylococcus aureus exhibits the capacity to develop biofilms on various surfaces, encompassing both living and nonliving substrates, enabling it to develop resistance against the immune system and antibiotics. Therefore, this bacterium can cause numerous challenges in healthcare and treatment systems. The present study aimed to investigate the ampicillin-loaded PLGA nanoparticles’ effect on preventing the methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation when it is conjugated with lysostaphin. With the use of the double emulsion evaporation technique, nanodrug carriers were created. Physicochemical attributes of the nanoparticles, such as particle size, drug loading, PDI, encapsulation efficiency, zeta potential, efficiency of lysostaphin conjugation, and morphology, were measured. Minimum inhibitory concentration (MIC), well diffusion, and other techniques were used to investigate the effect of the produced nanodrug carrier on strains of S. aureus. A toxicity test was conducted to examine the toxic effects of artificially generated nanomedicines on the L929 fibroblast culture. The nanoparticle average size, zeta potential, PDI, lysostaphin conjugation efficiency and drug loading encapsulation efficiency, and in the optimum PLGA-AMP-LYS (F4) formulation were 301.9 ± 32 nm, 0.261 ± 0.010, −19.2 ± 3.4 mV, 18.916 ± 1.6, and 94.53 ± 3.8, 40%, respectively. After 72 hours, neither the well diffusion nor MIC techniques revealed any discernible variation between ampicillin and nanodrug carriers. The biofilm investigation’s findings, however, indicated that compared to the free drug, the hindering effect of the nanodrug carrier was greater after 72 hours. The toxicity test findings revealed that the synthesized nanodrug had no toxic effects on the cells. Given the excellent efficacy of the nanomedicine carrier established in the present study, applying this technology to combat hospital-acquired infections caused by Staphylococcus bacteria could yield significant benefits in managing staphylococcal infections.
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载氨苄西林聚乳酸-羟基乙酸纳米颗粒结合溶葡萄球菌对耐甲氧西林金黄色葡萄球菌的抗生物膜作用
金黄色葡萄球菌表现出在各种表面上形成生物膜的能力,包括生物和非生物底物,使其能够对免疫系统和抗生素产生耐药性。因此,这种细菌会给医疗保健和治疗系统带来许多挑战。本研究旨在研究负载氨苄西林的PLGA纳米颗粒与溶葡萄球菌蛋白结合时对耐甲氧西林金黄色葡萄球菌(MRSA)生物膜形成的抑制作用。采用双乳蒸发技术制备了纳米药物载体。测定了纳米颗粒的物理化学性质,如粒径、载药量、PDI、包封效率、zeta电位、溶葡萄球菌蛋白偶联效率和形态。采用最小抑制浓度(MIC)、孔扩散等技术研究了制备的纳米药物载体对金黄色葡萄球菌菌株的影响。采用毒性试验研究人工合成纳米药物对L929成纤维细胞的毒性作用。最佳PLGA-AMP-LYS (F4)配方的纳米颗粒平均粒径为301.9±32 nm, zeta电位为0.261±0.010,PDI为- 19.2±3.4 mV, 18.916±1.6 mV, 94.53±3.8 mV,载药包封率为40%。72小时后,孔扩散和MIC技术都没有发现氨苄西林和纳米药物载体之间有任何明显的差异。然而,生物膜研究结果表明,与游离药物相比,纳米药物载体在72小时后的阻碍作用更大。毒性试验结果表明,合成的纳米药物对细胞无毒性作用。鉴于本研究中建立的纳米药物载体的优异疗效,将该技术应用于对抗葡萄球菌引起的医院获得性感染可能会在葡萄球菌感染的管理方面产生显著的好处。
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