Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms
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RESEARCH PAPER
Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms A r a m M o h a m m e d 1 & J a k u b Z u r e k 1 & S o m t o M a d u e k e 1 & H a r e i r A l - Ka s s i m y 1 & Muhammad Yaqoob 2 & Chahinez Houacine 3 & Amina Ferraz 3 & R achith Kalgudi 4 & Mohammed Gulrez Zariwala 4 & Nicholas Hawkins 5 & Hisham Al-Obaidi 1
Received: 26 May 2020 / Accepted: 8 July 2020 # The Author(s) 2020
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
* Hisham Al-Obaidi [email protected] 1
The School of Pharmacy, University of Reading, Reading RG6 6AD, UK
2
Interaction Chempharm Ltd, Reading RG2 0QX, UK
3
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK
4
School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK
5
Department of Engineering Science, University of Oxford, Parks Road, 0X1 3PJ, Oxford, UK
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.
KEY WORDS ciprofloxacin . Co-amorphous . effervescent . dry powder inhaler . Pseudomonas aeruginosa
ABBREVIATIONS CFX CPF DOE ED EFPF FPD GSD MMAD PFF TA
ciprofloxacin (Coarse particle fraction) design of experiments (Emitted Dose) (Extra-fine particle fraction) (Fine particle dose) (geometric standard deviation) (mass median aerodynamic diameter) (Fine particle fraction) tartaric acid
INTRODUCTION Biofilms are highly dense collection of microbial cells embedded within a self-produced matrix of exopolysaccharide (EPS) (1). The composition of this bacterial matrix can significantly vary but generally it is composed of a polysaccharide rich structure with proteins and DNA (2,3). While this multila
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