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 antimic...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-04-01
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| Series: | npj Antimicrobials and Resistance |
| Online Access: | https://doi.org/10.1038/s44259-025-00086-3 |
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| author | Victor Choi Dario Carugo Eleanor Stride |
| author_facet | Victor Choi Dario Carugo Eleanor Stride |
| author_sort | Victor Choi |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-2a48708bee43405a8af6d3d5526c733f |
| institution | DOAJ |
| issn | 2731-8745 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Antimicrobials and Resistance |
| spelling | doaj-art-2a48708bee43405a8af6d3d5526c733f2025-08-20T03:08:09ZengNature Portfolionpj Antimicrobials and Resistance2731-87452025-04-013111610.1038/s44259-025-00086-3Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug deliveryVictor Choi0Dario Carugo1Eleanor Stride2Department of Engineering Science, Institute of Biomedical Engineering, University of OxfordNuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of OxfordDepartment of Engineering Science, Institute of Biomedical Engineering, University of OxfordAbstract 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.https://doi.org/10.1038/s44259-025-00086-3 |
| spellingShingle | Victor Choi Dario Carugo Eleanor Stride Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery npj Antimicrobials and Resistance |
| title | Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery |
| title_full | Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery |
| title_fullStr | Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery |
| title_full_unstemmed | Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery |
| title_short | Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery |
| title_sort | repurposing antimicrobials with ultrasound triggered nanoscale systems for targeted biofilm drug delivery |
| url | https://doi.org/10.1038/s44259-025-00086-3 |
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