Generation of High Dose Inhalable Effervescent Dispersions against Pseudomonas aeruginosa Biofilms

Aram Mohammed,Somto Madueke,Mohammed Gulrez Zariwala,Muhammad Yaqoob,Jakub Zurek,Hisham Al-Obaidi,Rachith Kalgudi,Nicholas Hawkins,Hareir Al-Kassimy,Chahinez Houacine,Amina Ferraz

doi:10.1007/s11095-020-02878-w

Abstract

PurposeNovel particle engineering approach was used in this study to generate high dose inhalable effervescent particles with synergistic effects against Pseudomonas aeruginosa biofilms.MethodsSpray 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.ResultsGenerated 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.ConclusionsOverall, these results showed the potential to use particle engineering to generate particles that are highly disruptive of bacterial biofilms.

Highlights

Biofilms are highly dense collection of microbial cells embedded within a self-produced matrix of exopolysaccharide (EPS) [1]
Diffusing wave spectroscopy results showed that the silver containing particles had a disruptive effect on rheological properties as opposed to silver free particles. Overall, these results showed the potential to use particle engineering to generate particles that are highly disruptive of bacterial biofilms
We identified three parameters that can affect the properties of the particles which were: CFX to tartaric acid (TA) molar ratio, ratio of ethanol to water in solution prior to spray drying and inlet temperature

Summary

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 multilayer 150 Page 2 of 14. Pharm Res (2020) 37: 150 structure is considered resistant to penetration of antibiotics, it is efficient for water and nutrients transports for the survival of the bacteria [4]. Its ability to form robust biofilms as part of the infection renders them chronic and difficult to treat there is an urgent need for synergistic antibiotic therapies [6]

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