Enhanced Eradication of Mucin-Embedded Bacterial Biofilm by Locally Delivered Antibiotics in Functionalized Microcontainers

Stine Egebro Birk*, Laura Serioli, Valentina Cavallo, Janus Anders Juul Haagensen, Søren Molin, Line Hagner Nielsen, Kinga Zór, Anja Boisen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Bacterial biofilm-related infections are difficult to eradicate and require repeated treatments with high doses of antibiotics. Thus, there is an urgent need for new treatment strategies that minimize the use of antibiotics while enhancing biofilm eradication. Functionalized reservoir-based microdevices, such as, microcontainers (MCs), offer, high drug loading capacity, mucus embedment, and tuneable drug release. Here, MCs are loaded with the antibiotic ciprofloxacin (CIP), and sealed with a lid consisting of chitosan (CHI) and a mucolytic agent, N-acetylcysteine (NAC). It is found that CHI and NAC work synergistically, showing improved mucoadhesive and mucolytic properties. To better mimic the in vivo habitat of Pseudomonas aeruginosa (P. aeruginosa), the biofilm is grown in a mucin-containing medium on a newly developed centrifugal microfluidic system. The CHI/NAC coated MCs improve eradication of biofilm (88.22 ± 2.89%) compared to CHI-coated MCs (72.68 ± 3.73%) or bolus injection (39.86 ± 13.28%). The findings suggest that MCs are significantly more efficient than a bolus treatment. Furthermore, CHI/NAC functionalized MCs kill most of the biomass already after 5 h (80.75 ± 3.50%), mainly due to a fast drug release. This is the first time that CHI/NAC has been combined as a coating to explore mucolytic properties on bacterial biofilms.

Original languageEnglish
Article number2100150
JournalMacromolecular Bioscience
Volume21
Issue number8
Number of pages10
ISSN1616-5187
DOIs
Publication statusPublished - 2021

Keywords

  • Artificial sputum medium
  • Chitosan
  • In vitro perfusion system
  • Microdevices
  • N-acetylcysteine
  • Pseudomonas aeruginosa biofilm

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