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Journal article

Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery

Abstract:
Chronic infections represent a major clinical challenge due to the enhanced antimicrobial tolerance of biofilm-dwelling bacteria. To address this challenge, an ultrasound-responsive nanoscale drug delivery platform (nanodroplets) is presented in this work, loaded with four different antimicrobial agents, capable of simultaneous biofilm disruption and targeted antimicrobial delivery. When loaded, a robust protective effect against clinically-derived MRSA and ESBL Gram-positive and Gram-negative planktonic isolates was shown in vitro. Upon application of therapeutic ultrasound, an average 7.6-fold, 44.4-fold, and 25.5-fold reduction was observed in the antibiotic concentrations compared to free drug required to reach the MBC, MBEC and complete persister eradication levels, respectively. Nanodroplets substantially altered subcellular distribution of encapsulated antimicrobials, enhancing accumulation of antimicrobials by 11.1-fold within the biofilm-residing bacteria’s cytoplasm compared to treatment with unencapsulated drugs. These findings illustrate the potential of this multifunctional platform to overcome the critical penetration and localization limitations of antimicrobials within biofilms, opening potential new avenues in the treatment of chronic clinical infections.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s44259-025-00086-3

Authors

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Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Sub department:
Institute of Biomedical Engineering
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDORMS
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Engineering Science
Sub department:
Institute of Biomedical Engineering
Role:
Author
ORCID:
0000-0003-3371-5929


More from this funder
Funder identifier:
https://ror.org/0439y7842
Grant:
EP/V026623/1


Publisher:
Springer Nature
Journal:
npj Antimicrobials and Resistance More from this journal
Volume:
3
Issue:
1
Article number:
22
Publication date:
2025-04-01
Acceptance date:
2025-02-06
DOI:
EISSN:
2731-8745


Language:
English
Pubs id:
2092935
Local pid:
pubs:2092935
Deposit date:
2025-03-01
ARK identifier:

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