Wound care
the biofilm, we add an ultrasound wave. This causes the little droplets to expand into much larger microbubbles, which oscillate in response to the ultrasound pressure and causes gaps to form. The fluid movement around the bubble helps the drugs penetrate inside the biofilm and kill the embedded bacteria.”
Gentamicin (shown above) typically doesn’t work against persister cells in biofilms, but palmitoleic acid works as an adjuvant to help it wipe them out.
“The idea is to develop nanoparticles that can penetrate biofilms,” she says. “These would be smart release carriers, which are triggered to release the antimicrobial when they reach the bacteria. That could be used either for preventing biofilm formation, or for disrupting current biofilms.”
While she is hopeful about the wave of research being conducted in this area, she points out it can be tricky to turn lab studies into real-world applications. What’s more, the disparate healthcare professionals involved in wound care tend to work in siloes. More translational research is needed, and the field needs to become more joined up.
“The idea is to develop nanoparticles that can penetrate biofilms. These would be smart release carriers, which are triggered to release the antimicrobial when they reach the bacteria. That could be used either for preventing biofilm formation, or for disrupting current biofilms.” Barbara Conway
“You can grow biofilms in the lab, but that biofilm
won’t be the same as it’s going to be in a wound,” she says. “People are different, the types of constituents in each wound are different, it changes over time, and you’ve got that complex ongoing healing process as well. That’s why a one-size-fits-all approach doesn’t work. We’re always after realistic models to use to test our formulations.”
A promising approach Across the Atlantic, Rowe-Conlon’s team have also been looking for ways to deliver antimicrobials through biofilms. Their approach combines a topical antibiotic (gentamicin), an antibiotic adjuvant (palmitoleic acid) and non-invasive ultrasound. It was used successfully in an animal model, reducing MRSA infection by 94% in the wounds of diabetic mice. “Our method, which we call sonotherapy, involves adding topical antibiotics on top of the wound, along with these nanoscale droplets,” says Rowe-Conlon. “Once the nanoscale droplets have penetrated inside
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Ultrasound-responsive microbubbles have been used for decades within diagnostic imaging, but they’ve only recently been tested within therapeutic applications. According to Virginie Papadopoulou, a research assistant professor in the UNC-NCSU Joint Department of Biomedical Engineering, and the ultrasound lead of the study, this is the first time they have been used topically rather than intravenously in vivo. “We just pipette them on top of the wound, to see if we can use them for drug delivery,” she says. “That's one aspect that's new – the nanoscale droplet formulation variant we’ve used allows for increased stability and penetration into the biofilm. We are also using a slightly different type of bubble. When we start our treatment, they’re tiny liquid droplets in a lipid shell. Once we apply the ultrasound, we can convert them back into a gas bubble about the size of a red blood cell.” What’s notable about this research is that the antibiotic chosen (gentamicin) is typically ineffective against MRSA. That’s because it performs badly against the persister cells. In this case, the palmitoleic acid works as a novel, non-toxic antibiotic adjuvant – helping the antibiotic wipe out the persister cells and even reversing antibiotic resistance. “Gentamicin is great at stopping the spread of the infection, but it's not very good at actually removing a biofilm infection,” says Rowe-Conlon. “Using our approach we can reduce the biofilm by 94%, and three of our eight mice had no detectable bacteria left in their wounds. We're very excited that this topical only, non-invasive approach is so effective at reducing the biofilm, compared to the standard of care.” The team at UNC are now looking to scale up their research into a larger animal model, and, if that works, a safety study in humans. While their technique is still a long way from the clinic, it could one day be used as an add-on therapy in multiple contexts. The ultrasound is portable (meaning it could be used in outpatient settings) and potentially compatible with any antibiotic. “There was a recent study that suggested by 2050, more people will succumb to antibiotic-resistant infections than currently succumb to cancer,” says Rowe-Conlon. “With the void in the drug development pipeline, we need strategies to make our current arsenal of antibiotics work better, rather than relying on the development of new molecules.” For anyone involved in chronic wound care – or in treating infections more generally – biofilms represent a challenging battlefront. Understanding their complexities will be key if we want to use antibiotics effectively and improve patients’ quality of life.
Practical Patient Care /
www.practical-patient-care.com
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