Gbian Douweh Leyla, Omri Abdelwahab
Department of Chemistry and Biochemistry, The Novel Drug and Vaccine Delivery Systems Facility, Laurentian University, Sudbury, ON P3E 2C6, Canada.
Pharmaceutics. 2021 Apr 18;13(4):577. doi: 10.3390/pharmaceutics13040577.
The eradication of in cystic fibrosis patients has become continuously difficult due to its increased resistance to treatments. This study assessed the efficacy of free and liposomal gentamicin and erythromycin, combined with Phenylalanine arginine beta-naphthylamide (PABN), a broad-spectrum efflux pump inhibitor, against isolates. Liposomes were prepared and characterized for their sizes and encapsulation efficiencies. The antimicrobial activities of formulations were determined by the microbroth dilution method. Their activity on biofilms was assessed, and the effect of sub-inhibitory concentrations on bacterial virulence factors, quorum sensing (QS) signals and bacterial motility was also evaluated. The average diameters of liposomes were 562.67 ± 33.74 nm for gentamicin and 3086.35 ± 553.95 nm for erythromycin, with encapsulation efficiencies of 13.89 ± 1.54% and 51.58 ± 2.84%, respectively. Liposomes and PABN combinations potentiated antibiotics by reducing minimum inhibitory and bactericidal concentrations by 4-32 fold overall. The formulations significantly inhibited biofilm formation and differentially attenuated virulence factor production as well as motility. Unexpectedly, QS signal production was not affected by treatments. Taken together, the results indicate that PABN shows potential as an adjuvant of liposomal macrolides and aminoglycosides in the management of lung infections in cystic fibrosis patients.
由于其对治疗的耐药性增加，根除囊性纤维化患者体内的（某种病菌，原文未明确）变得愈发困难。本研究评估了游离型和脂质体型庆大霉素及红霉素，联合广谱外排泵抑制剂苯丙氨酸精氨酸β-萘酰胺（PABN）对（某种病菌，原文未明确）分离株的疗效。制备了脂质体并对其大小和包封效率进行了表征。通过微量肉汤稀释法测定制剂的抗菌活性。评估了它们对（某种病菌，原文未明确）生物膜的活性，还评估了亚抑菌浓度对细菌毒力因子、群体感应（QS）信号和细菌运动性的影响。庆大霉素脂质体的平均直径为562.67±33.74 nm，红霉素脂质体的平均直径为3086.35±553.95 nm，包封效率分别为13.89±1.54%和51.58±2.84%。脂质体与PABN的组合总体上通过将最低抑菌浓度和杀菌浓度降低4至32倍来增强抗生素作用。这些制剂显著抑制生物膜形成，并不同程度地减弱毒力因子产生以及运动性。出乎意料地，QS信号产生不受治疗影响。综上所述，结果表明PABN在囊性纤维化患者肺部感染管理中作为脂质体大环内酯类和氨基糖苷类的佐剂具有潜力。
