Department of Microbiology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
School of Pharmacy, The University of Queensland, Woolloongabba 4102, Australia.
NanoImpact. 2022 Jan;25:100384. doi: 10.1016/j.impact.2022.100384. Epub 2022 Jan 24.
Staphylococcus aureus (S. aureus) biofilm-associated infections are a primary concern for public health worldwide. Current therapeutics cannot penetrate the biofilms efficiently, resulting in low drug concentrations at the infected sites and increasing the frequency of drug usage. To solve this issue, nanotechnology platforms seem to be a promising approach. In this study, the potential therapeutic effects of (PEG)ylated liposome (PEG-Lip) for the delivery of nafcillin (NF) antibiotic were assessed. The results demonstrated that NF-loaded liposome (Lip-NF) and NF-loaded PEG-Lip (PEG-Lip-NF) released 76.4 and 62% of the loaded NF, respectively, in a controlled manner after 50 h. Also, it was found that PEG-Lip-NF, compared to Lip-NF and NF, was more effective against a methicillin-susceptible S. aureus (MSSA; minimum inhibitory concentration (MIC): 1.0 ± 0.03, 0.5 ± 0.02, and 0.25 ± 0.01 μg/mL; and minimum biofilm inhibitory concentration (MBIC): 4.0 ± 0.18, 1.0 ± 0.04, and 0.5 ± 0.02 μg/mL for NF, Lip-NF, and PEG-Lip-NF, respectively). PEG-Lip-NF, compared to NF and Lip-NF, could also more efficiently decrease the side effects of NF through improving human MG-63 osteoblast cell viability (cell viability at 100 μM of NF: 76, 68, and 38% for PEG-Lip-NF, Lip-NF, and NF, respectively). PEG-Lip-NF, compared to control, NF, and Lip-NF groups, was more efficacious by 45, 25, and 10%, respectively, to decrease the virulence of MSSA bacteremia through inhibiting the weight loss of the infected mice. Also, PEG-Lip-NF and Lip-NF, compared to control and NF groups, caused a considerable decrease in the mortality rate in a murine model of bacteremia (number of dead mice: 0, 0, 2, and 8 out of 15 for PEG-Lip-NF, Lip-NF, NF, and control groups, respectively). Overall, the results of this study demonstrated that the loading of NF into PEG-Lip is a promising strategy to decrease the side effects of NF with improved antibacterial effects for the treatment of MSSA biofilm-associated infections.
金黄色葡萄球菌（S. aureus）生物膜相关感染是全球公共卫生的主要关注点。目前的治疗方法无法有效地穿透生物膜，导致感染部位的药物浓度较低，并增加了药物使用的频率。为了解决这个问题，纳米技术平台似乎是一种有前途的方法。在这项研究中，评估了（PEG）化脂质体（PEG-Lip）递送萘夫西林（NF）抗生素的潜在治疗效果。结果表明，负载 NF 的脂质体（Lip-NF）和负载 NF 的 PEG-Lip（PEG-Lip-NF）分别在 50 小时后以受控方式释放了 76.4%和 62%的负载 NF。此外，与 Lip-NF 和 NF 相比，PEG-Lip-NF 对耐甲氧西林金黄色葡萄球菌（MSSA；最小抑菌浓度（MIC）：1.0±0.03、0.5±0.02 和 0.25±0.01μg/mL；最小生物膜抑制浓度（MBIC）：4.0±0.18、1.0±0.04 和 0.5±0.02μg/mL）更有效。与 NF 和 Lip-NF 相比，PEG-Lip-NF 还可以通过提高人 MG-63 成骨细胞的活力来更有效地降低 NF 的副作用（在 100μM NF 时的细胞活力：PEG-Lip-NF、Lip-NF 和 NF 分别为 76%、68%和 38%）。与对照组、NF 组和 Lip-NF 组相比，PEG-Lip-NF 分别以 45%、25%和 10%的效率降低 MSSA 菌血症的毒力，通过抑制感染小鼠的体重减轻。此外，与对照组和 NF 组相比，PEG-Lip-NF 和 Lip-NF 导致菌血症的小鼠模型的死亡率显著降低（PEG-Lip-NF、Lip-NF、NF 和对照组的死亡小鼠数分别为 0、0、2 和 8）。总体而言，这项研究的结果表明，将 NF 加载到 PEG-Lip 中是一种有前途的策略，可以降低 NF 的副作用，同时提高抗菌效果，用于治疗 MSSA 生物膜相关感染。
