Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.
Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.
Biomaterials. 2023 May;296:122071. doi: 10.1016/j.biomaterials.2023.122071. Epub 2023 Feb 28.
Lung bacterial infections could result in acute lung inflammation/injury (ALI) that propagates to its severe form, acute respiratory distress syndrome (ADRS) leading to the death. The molecular mechanism of ALI is associated with bacterial invasion and the host inflammation response. Here, we proposed a novel strategy to specifically target both bacteria and inflammatory pathways by co-loading of antibiotics (azlocillin, AZ) and anti-inflammatory agents (methylprednisolone sodium, MPS) in neutrophil nanovesicles. We found that cholesterol infilling in the membrane of nanovesicles can maintain a pH gradient between intra-vesicles and outer-vesicles, so we remotely loaded both AZ and MPS in single nanovesicles. The results showed that loading efficiency of both drugs can achieve more than 30% (w/w), and delivery of both drugs using nanovesicles accelerated bacterial clearance and resolved inflammation responses, thus preventing the potential lung damage due to infections. Our studies show that remote loading of multiple drugs in neutrophil nanovesicles which specifically target the infectious lung could be translational to treat ARDS.
肺部细菌感染可能导致急性肺炎症/损伤（ALI），进而发展为严重的急性呼吸窘迫综合征（ARDS），导致死亡。ALI 的分子机制与细菌入侵和宿主炎症反应有关。在这里，我们提出了一种新的策略，通过在中性粒细胞纳米囊泡中共同装载抗生素（氨曲南，AZ）和抗炎剂（甲泼尼龙钠，MPS）来特异性靶向细菌和炎症途径。我们发现，胆固醇填充在纳米囊泡的膜中可以在囊内和囊外之间维持 pH 梯度，因此我们可以远程将 AZ 和 MPS 装载到单个纳米囊泡中。结果表明，两种药物的装载效率都可以达到 30%（w/w）以上，并且使用纳米囊泡递送两种药物可以加速细菌清除和缓解炎症反应，从而防止由于感染引起的潜在肺部损伤。我们的研究表明，将多种药物远程装载到专门针对感染性肺部的中性粒细胞纳米囊泡中，可能会转化为治疗 ARDS 的方法。
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