Abstract

Purpose

Novel particle engineering approach was used in this study to generate high dose inhalable effervescent particles with synergistic effects against Pseudomonas aeruginosa biofilms.

Methods

Spray dried co-amorphous salt of ciprofloxacin (CFX) and tartaric acid (TA) was prepared and coated with external layer of sodium bicarbonate and silica coated silver nanobeads. Design of experiments (DOE) was used to optimize physicochemical properties of particles for enhanced lung deposition.

Results

Generated particles were co-amorphous CFX/TA showing that CFX lost its zwitterionic form and exhibiting distinct properties to CFX/HCl as assessed by FTIR and thermal analysis. Particles exhibited mass mean aerodynamic diameter (MMAD) of 3.3 μm, emitted dose of 78% and fine particle dose of 85%. Particles were further evaluated via antimicrobial assessment of minimum inhibitory concentrations (MIC) and minimum biofilm eradication concentration (MBEC). MIC and MBEC results showed that the hybrid particles were around 3–5 times more effective when compared to CFX signifying that synergistic effect was achieved. Diffusing wave spectroscopy results showed that the silver containing particles had a disruptive effect on rheological properties as opposed to silver free particles.

Conclusions

Overall, these results showed the potential to use particle engineering to generate particles that are highly disruptive of bacterial biofilms.

中文翻译：

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针对铜绿假单胞菌生物膜的高剂量吸入泡腾分散剂的生成。

 抽象的

 目的

本研究采用新型颗粒工程方法来产生高剂量可吸入泡腾颗粒，对铜绿假单胞菌生物膜具有协同作用。

 方法

制备喷雾干燥的环丙沙星（CFX）和酒石酸（TA）的共无定形盐，并用碳酸氢钠和二氧化硅涂覆的银纳米珠外层涂覆。实验设计 (DOE) 用于优化颗粒的物理化学性质，以增强肺部沉积。

 结果

生成的颗粒是共无定形 CFX/TA，表明 CFX 失去了两性离子形式，并通过 FTIR 和热分析评估显示出与 CFX/HCl 不同的特性。颗粒物的质量平均空气动力学直径 (MMAD) 为 3.3 μm，发射剂量为 78%，细颗粒剂量为 85%。通过最小抑菌浓度 (MIC) 和最小生物膜根除浓度 (MBEC) 的抗菌评估进一步评估颗粒。 MIC 和 MBEC 结果表明，与 CFX 相比，混合颗粒的效果大约高 3-5 倍，这表明实现了协同效应。扩散波光谱结果表明，与不含银的颗粒相比，含银颗粒对流变性能具有破坏性影响。

 结论

总的来说，这些结果表明使用粒子工程产生对细菌生物膜具有高度破坏性的粒子的潜力。