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

    Year: 2021

    Journal: Macromol. Biosci., Volume 21, AUG

    Authors: Birk, Stine Egebro; Serioli, Laura; Cavallo, Valentina; Haagensen, Janus Anders Juul; Molin, Soren; Nielsen, Line Hagner; Zor, Kinga; Boisen, Anja

    Organizations: Danish National Research Foundation [DNRF122]; Villum Foundation [9301]

    Keywords: artificial sputum medium; chitosan; in vitro perfusion system; microdevices; N-acetylcysteine; Pseudomonas aeruginosa biofilm

    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.
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