Microbial biofilms are the bane of chronic wound sufferers and wound care specialists, but a new study has found ionic liquids can disrupt these biofilms without irritating the already damaged tissue.
Biofilms adhere to a surface, often the skin, and impair the healing process. Affixed to each other by self-produced secretions of polysaccharides, proteins and other substances, and shielded by these secretions and the outermost layer of skin under which they often form, these microbes are able to resist antibiotics and continue to prey on the tissue beneath. The results are wounds that are slow to heal, or continue to reappear. Its painful and expensive: In the U.S. last year, as much as $75 billion was spent on the treatment of recurring and resistant wounds.
Researchers at UC Santa Barbaras Center for BioEngineering and its department of chemical engineering have found ionic liquids not only disrupt the biofilms, which increases the effectiveness of accompanying antibiotics, but also they do so with virtually no irritation and inflammation of the already damaged tissue.
The findings also show some ionic liquids are often capable of neutralizing pathogens, even without the use of antibiotics.
Their results were published in the Sept. 16 issue of the Proceedings of the National Academy of Sciences.
The challenge was how to find a chemical, or a composition of chemicals, that are toxic to bacteria they disrupt the biofilm and enhance the transport of antibiotic drugs but do not kill the healthy mammalian cells or cause inflammation to the skin, senior author Samir Mitragotri, PhD, CBE director, said in a news release. Mitragotri specializes in targeted drug delivery.
Ionic liquids are essentially salts pairings of positively charged cations and negatively charged anions that exist in liquid form below 100 degrees Celsius. These liquids have been known to scientists for more than a century and are used in applications such as solvents, additives and electrolytes.
For the study, Mitragotri, UC doctoral candidate Michael Zakrewsky and the team synthesized several common and novel ionic liquids and assessed their performance on a biofilm on a wound model. They studied the liquids ability to break up the biofilm and enhance drug delivery, while also studying toxicity and antimicrobial activity. Of the liquids they studied, one called choline-geranate emerged as a multipurpose ionic liquid that fit the researchers criteria most effectively.
Choline-geranate was comparable to or even more effective than bleach against biofilms established by Salmonella enterica, a common cause of food poisoning, and Pseudomonas aeruginosa, a widespread bacteria that exists in many environments, the study showed. The liquid also proved to be nonirritating and noninflammatory. The team also found even without an antibiotic, choline-geranate was effective against the target bacteria.
Ionic liquids are relatively easy to modify, so they can be used as multipurpose antimicrobials, like choline-geranate, Zakrewsky, the lead author, said in the release. Or they can be adjusted to the specific properties and microbes in the biofilm, even those that have become resistant to antibiotics.
Its really the fact that you have this one cation and one anion that you can tune individually within the pair that allows it to be very multifunctional, Zakrewsky said in the release. So we can choose one component that we know helps transport through the skin, and we can choose one component that we know disrupts biofilms.
As microbial biofilm disruptors, ionic liquids are good news for those who suffer chronic wounds, such as those related to diabetes, or suppressed immunities. Not only can ionic liquids destroy existing biofilms, which over time can become resistant to treatment, but also they can do so without inflammation that restricts the healing process. According to Scott Hammond, MD, executive director of UCSBs Translational Medicine Research Laboratories, ionic liquids also can be used to prevent infections from invasive procedures, to treat surfaces that can become the site of biofilms such as implanted devices, surgical equipment and contact lenses, and to care for chronic ulcers.
Chronic wounds are interesting to me because these patients come in two to three times a week for perpetuity, and we have completely hit a wall on what to do, Hammond said in the release. Theres a whole spectrum of what we can do here.
Hammond added their use of pre-emptive practices and real-time profiling of patient and bacteria can result in improved therapy and ultimately, less costly and more accessible healthcare.
The team collaborated with researchers at Los Alamos National Laboratory in New Mexico; Dixie State University in St. George, Utah; and Northern Arizona University in Flagstaff.