TY - JOUR
T1 - Enhanced Eradication of Mucin-Embedded Bacterial Biofilm by Locally Delivered Antibiotics in Functionalized Microcontainers
AU - Birk, Stine Egebro
AU - Serioli, Laura
AU - Cavallo, Valentina
AU - Haagensen, Janus Anders Juul
AU - Molin, Søren
AU - Nielsen, Line Hagner
AU - Zór, Kinga
AU - Boisen, Anja
N1 - Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Artificial sputum medium
KW - Chitosan
KW - In vitro perfusion system
KW - Microdevices
KW - N-acetylcysteine
KW - Pseudomonas aeruginosa biofilm
U2 - 10.1002/mabi.202100150
DO - 10.1002/mabi.202100150
M3 - Journal article
C2 - 34117842
AN - SCOPUS:85105689855
SN - 1616-5187
VL - 21
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 8
M1 - 2100150
ER -