Biofilms are aggregates of microorganisms embedded in a self-produced extracellular matrix and can attach to each other or to surfaces, including a patient’s skin or soft tissue, or an implanted medical device, such as a catheter. Microorganisms that make up biofilms can include bacteria, fungi, and protists. Biofilms are prevalent in many infections and are resistant to therapeutic agents, such as antibiotics, because biofilms are formed of multiple layers of microorganisms encapsulated in a polysaccharide matrix. This results in a physical barrier that makes it difficult for the antibiotic to penetrate and to reach the deeper layers of the biofilm. In addition, the deeper layers of a biofilm are often oxygen or nutrient deplete environments, resulting in a low metabolic state, making antibiotics less effective because they target metabolic-dependent processes. When an antibiotic course fails to treat an infection, there are often subsequent chronic and persistent infections for the patient, the potential development of antibiotic resistance, and increased financial burdens on the patient and healthcare system. This highlights the need for novel approaches for disrupting biofilms to enhance delivery and efficacy of therapeutic agents.
Researchers in the Department of Biomedical Engineering at the University of North Carolina at Chapel Hill and the Department of Material Science and Engineering at the University of Colorado Boulder have developed a novel method to deliver therapeutics and disrupt biofilms by using ultrasound activated nanodrops, which leads to increased penetration and efficacy of the therapeutic. Upon ultrasound activation, the nanodrops convert from a liquid phase to a gas phase, resulting in a microbubble. This phase change to microbubbles results in continuous expansion and contraction, inducing shear stress on the biofilm. Additionally, the microbubbles can also be induced to create a microjet to physically puncture the bacterial cells and disrupt the physical make up of the biofilm. Using ultrasound activated nanodrops to disrupt and deliver antibiotics, such as vancomycin or tobramycin, to MRSA (methicillin resistant S. aureus) biofilm in vitro, there is an increased delivery and efficacy for treating the biofilm when compared to treatment with an antibiotic alone.
Physical disruption of biofilms leading to increased delivery of therapeutic agents.
Increased efficacy of therapeutic agents.
Treatment of antibiotic resistant infections and decreased likelihood of the development of antibiotic resistance.
This novel method for delivering therapeutics to biofilms can be used to treat problematic infectious associated with biofilms such as, antibiotic resistant infections and chronic wounds.
- Harnessing Ultrasound-Stimulated Phase Change Contrast Agents to Improve Antibiotic Efficacy Against Methicillin-Resistant Staphylococcus aureus Biofilms Phillip G. Durham, Ashelyn E. Sidders, Paul A. Dayton, Brian P. Conlon, Virginie Papadopoulou, Sarah E. Rowe bioRxiv 2020.06.01.127340; doi: https://doi.org/10.1101/2020.06.01.127340