Crowther, Aaron;
(2025)
The combined effects of biofilm dispersal agents and ultrasound: a novel therapeutic strategy for biofilm-associated infections.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Biofilm-associated infections (BAIs) account for up to 80% of human infections, often contributing to chronicity and antibiotic resistance. Biofilms, commonly found in chronic wounds and urinary tract infections (UTIs), create a diffusional barrier that limits antimicrobial penetration and provide a niche for dormant, antibiotic-tolerant bacteria. Novel antibiofilm agents, including the signalling molecule nitric oxide (NO) and the chelator tetrasodium ethylenediaminetetraacetic acid (T-EDTA), show promise due to their multifaceted effects, such as bactericidal activity, biofilm dispersal, and wound healing. Additionally, ultrasound (US)-mediated cavitation has emerged as a potential adjuvant therapy, enhancing antimicrobial penetration by physically disrupting the biofilm architecture. This study investigates the combination of chemical antibiofilm agents with US-mediated cavitation. NO-producing molecules propylamine propylamine NONOate (PA-NO) and spermine NONOate (SP-NO) and chelator TEDTA were evaluated against early-stage (24-hour) and mature (48-hour) Pseudomonas aeruginosa PAO1 biofilms. T-EDTA demonstrated consistent antibiofilm efficacy, reducing biofilm biomass by 57% (early-stage) and 64% (mature) after a 2- hour exposure period. After the same treatment period, PA-NO was effective against early-stage biofilms (21% reduction) but had no effect on mature biofilms, whilst SPNO showed no efficacy against either model. Two cationic microbubble (MB) formulations, room-air-core (RAMB+s) and perfluorobutane-core (PFBMB+s), were tested for stability and cavitation activity. PFBMB+ s exhibited superior stability and cavitation activity. When stimulated with US in the presence of ciprofloxacin, PFBMB+s combined with PA-NO achieved a 91.4% reduction in biofilm coverage, while T-EDTA showed reductions of 85.7% (without ciprofloxacin) and 88.2% (with ciprofloxacin). SP-NO remained ineffective in all conditions tested. These findings underscore the potential of combining NO donors or T-EDTA with US-stimulated MBs. Findings from this study suggest that the combination of biofilm dispersal compounds with cavitationmediated approaches represent a promising strategy for addressing the challenges of BAIs, particularly through enhancement of antimicrobial delivery and efficacy.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | The combined effects of biofilm dispersal agents and ultrasound: a novel therapeutic strategy for biofilm-associated infections |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10209199 |
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