针对铜绿假单胞菌生物膜的高剂量可吸入泡腾分散体制备。
Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms.
机构信息
The School of Pharmacy, University of Reading, Reading, RG6 6AD, UK.
Interaction Chempharm Ltd, Reading, RG2 0QX, UK.
出版信息
Pharm Res. 2020 Jul 19;37(8):150. doi: 10.1007/s11095-020-02878-w.
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.
目的
本研究采用新型粒子工程方法，制备具有协同作用的高剂量可吸入泡腾颗粒，以对抗铜绿假单胞菌生物膜。
方法
制备并包衣环丙沙星（CFX）和酒石酸（TA）共无定形盐的喷雾干燥颗粒，外部层为碳酸氢钠和涂有银纳米珠的硅酸钠。采用实验设计（DOE）优化颗粒的理化性质，以增强肺部沉积。
结果
生成的颗粒为 CFX/TA 共无定形物，表明 CFX 失去了两性离子形式，并通过傅里叶变换红外光谱（FTIR）和热分析显示出与 CFX/HCl 不同的特性。颗粒的质量中值空气动力学直径（MMAD）为 3.3μm，发射剂量为 78%，细颗粒剂量为 85%。进一步通过最低抑菌浓度（MIC）和最低生物膜清除浓度（MBEC）的抗菌评估来评估颗粒。MIC 和 MBEC 结果表明，与 CFX 相比，混合颗粒的效果提高了约 3-5 倍，表明达到了协同作用。扩散波光谱结果表明，与不含银的颗粒相比，含银的颗粒对流变性质具有破坏作用。
结论
总的来说，这些结果表明，利用粒子工程生成能够高度破坏细菌生物膜的粒子具有潜力。
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