Researchers at the University of Oxford have pioneered a novel drug delivery system that utilizes ultrasound-activated nanoparticles to penetrate and eradicate bacterial biofilms. This innovative approach offers a promising solution to the growing global challenge of chronic antibiotic-resistant infections, which affect hundreds of millions of individuals worldwide. The study was published in the journal npj Antimicrobials and Resistance.
The nanobubbles used in the study. Image Credit: Christopher Campbell.
Up to 80% of chronic infections involve bacteria-forming biofilms. Biofilms are a major contributor to antimicrobial resistance because they shield bacteria from the body's immune cells and antimicrobial drugs, making them up to 1000 times more resistant to treatment. Removing biofilms is particularly challenging without physically breaking them down, which is difficult to achieve inside the body.
To overcome this obstacle, a collaborative team from Oxford's Department of Engineering Science and the Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences (NDORMS) has engineered nanoparticles loaded with antibiotics. When these nanoparticles are activated by ultrasound, they rapidly vaporize, causing both physical disruption of the biofilms and direct release of the drugs at the infection site. A key advantage of this method is that ultrasound can be precisely focused deep within the body, allowing for non-invasive targeting of infections.
Innovative solutions are desperately needed to extend the action of life-saving antibiotics. Our findings are very promising, as treatment of chronic infections associated with biofilm production continues to be a challenge in the face of spreading antimicrobial resistance worldwide. The methods we used in this study were designed with clinical use in mind, and we look forward to developing this system further for application in healthcare settings.
Eleanor Stride, Professor and Study Principal Investigator, Biomaterials, University of Oxford
The nanoparticles were tested against 10 clinical bacterial strains, including E. Coli and methicillin-resistant Staphylococcus aureus (MRSA), delivering four different antibiotics. In tests against bacteria that did not form biofilms, the combination of the nanoparticles and ultrasound reduced the antibiotic concentration needed to inhibit their growth by more than 10 times compared to conventional treatment.
The combination proved even more effective against biofilm infections, reducing the required antibiotic concentration by over 40 times and completely eliminating 100% of the bacteria at clinically achievable doses. Notably, the system was highly effective against persister cells – dormant bacteria that typically survive treatment and are responsible for recurring infections.
Killing these cells often requires very high antibiotic doses, which can be dangerous or impossible for patients. The nanoparticles reduced the drug concentration needed to eliminate persister cells by 25 times compared to using free antibiotics.
Biofilms are implicated in numerous difficult-to-treat infections, including chronic wounds, urinary tract infections, lung infections associated with cystic fibrosis, and acne. The research team is now focused on scaling up the nanoparticle manufacturing process to facilitate clinical trials as soon as possible.
Journal Reference:
Choi, V., et al. (2025) Repurposing antimicrobials with ultrasound-triggered nanoscale systems for targeted biofilm drug delivery. npj Antimicrobials and Resistance. doi.org/10.1038/s44259-025-00086-3