Drug Delivery System Uses Ultrasound-Activated Nanoparticles to Destroy Bacterial Biofilms

In as many as 80% of chronic infections, bacteria form biofilms—slimy substances secreted by bacteria that create a protective matrix around them. Biofilms play a significant role in antimicrobial resistance, as they shield bacteria from both human immune responses and antimicrobial drugs, increasing their resistance to treatment by up to 1000 times. These biofilms are found in various difficult-to-treat infections, including chronic wounds, urinary tract infections, cystic fibrosis-related lung infections, and even acne. Biofilms are particularly challenging to remove without mechanically breaking them up, which is not easy to do within the body. Researchers have now developed a novel drug delivery system using ultrasound-activated nanoparticles to penetrate and destroy bacterial biofilms.

Researchers at the University of Oxford (Oxford, UK) achieved this by engineering antibiotic-loaded nanoparticles, that, when activated by ultrasound, rapidly vaporize. This vaporization not only disrupts biofilms physically but also releases drugs directly at the infection site. A key advantage of this approach is that ultrasound can be precisely targeted deep within the body, offering a non-invasive way to treat infections. The nanoparticles were tested on 10 clinical bacterial strains, including E. Coli and methicillin-resistant Staphylococcus aureus (MRSA), delivering four different antibiotics. For bacteria that did not form biofilms, the combination of nanoparticles and ultrasound reduced the amount of antibiotic required to inhibit bacterial growth by more than 10 times compared to conventional treatments.

The study, published in npj Antimicrobials and Resistance, showed that the combination of nanoparticles and ultrasound was even more effective in biofilm infections, reducing the antibiotic concentration required by more than 40-fold, and completely eliminating 100% of the bacteria at clinically feasible doses. A critical finding was that this system proved highly effective against persister cells—dormant bacteria that typically survive treatments and are responsible for infections recurring. To eliminate these persister cells, very high doses of antibiotics are often required, which can be dangerous or impossible to administer to patients. The nanoparticles reduced the drug concentration necessary to kill persister cells by 25 times compared to conventional antibiotics. The team is now working on optimizing the nanoparticle manufacturing process so that it can be tested in clinical settings as soon as possible.

“Innovative solutions are desperately needed to extend the action of life-saving antibiotics,” said Professor Eleanor Stride, Professor of Biomaterials, University of Oxford and Principal Investigator of the project. “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.”