Co-delivery of ciprofloxacin and colistin using microcontainers for bacterial biofilm treatment

[Display omitted] •Microcontainers (MCs) are co-loaded with ciprofloxacin/colistin and chitosan-sealed.•The two antibiotics show full eradication of P. aeruginosa in a time-kill study.•MCs create immediate high local drug concentrations in the biofilm.•Co-loaded MCs work faster than antibiotic solutions on P. aeruginosa biofilm. In many infected patients, bacterial biofilms represent a mode of growth that significantly enhances the tolerance to antimicrobials, leaving the patients with difficult-to-cure infections. Therefore, there is a growing need for effective treatment strategies to combat biofilm infections. In this work, reservoir-based microdevices, also known as microcontainers (MCs), are co-loaded with two antibiotics: ciprofloxacin hydrochloride (CIP) and colistin sulfate (COL), targeting both metabolically active and dormant subpopulations of the biofilm. We assess the effect of the two drugs in a time-kill study of planktonic P. aeruginosa and find that co-loaded MCs are superior to monotherapy, resulting in complete killing of the entire population. Biofilm consortia of P. aeruginosa grown in flow chambers were not fully eradicated. However, antibiotics in MCs work significantly faster than simple perfusion of antibiotics (62.5 ± 8.3% versus 10.6 ± 10.1% after 5 h) in biofilm consortia, showing the potential of the MC-based treatment to minimize the use of antimicrobials in future therapies.