Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms

被引:9
作者
Mohammed, Aram [1 ]
Zurek, Jakub [1 ]
Madueke, Somto [1 ]
Al-Kassimy, Hareir [1 ]
Yaqoob, Muhammad [2 ]
Houacine, Chahinez [3 ]
Ferraz, Amina [3 ]
Kalgudi, Rachith [4 ]
Zariwala, Mohammed Gulrez [4 ]
Hawkins, Nicholas [5 ]
Al-Obaidi, Hisham [1 ]
机构
[1] Univ Reading, Sch Pharm, Reading RG6 6AD, Berks, England
[2] Interact Chempharm Ltd, Reading RG2 0QX, Berks, England
[3] Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston PR1 2HE, Lancs, England
[4] Univ Westminster, Sch Life Sci, 115 New Cavendish St, London W1W 6UW, England
[5] Univ Oxford, Dept Engn Sci, Parks Rd, Oxford OX1 3PJ, England
关键词
ciprofloxacin; Co-amorphous; effervescent; dry powder inhaler; Pseudomonas aeruginosa; PHARMACEUTICAL COCRYSTALS; DRY POWDERS; LACTOSE; ACID; CIPROFLOXACIN; FORMULATION; INHALATION; GROWTH;
D O I
10.1007/s11095-020-02878-w
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose Novel particle engineering approach was used in this study to generate high dose inhalable effervescent particles with synergistic effects againstPseudomonas aeruginosabiofilms. 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 mu m, 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.
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页数:14
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