Compounds called ionic liquids penetrate biofilms, skin to deliver antibiotics
Quirky chemical compounds called ionic liquids can defeat the tricky defenses of bacteria and skin and help bring antibiotics to infections that can lead to discomfort, amputations and sometimes death, a new study finds.
“This work is a further demonstration of the potential of ionic liquids not only as a source of much needed chemical diversity in the hunt for new designer antimicrobial agents but also to enhance the activity of conventional antimicrobial agents,” says Brendan Gilmore, a microbiologist at Queen's University Belfast in Northern Ireland. “The promise of using ionic liquids to enhance the activity of antibiotics may increase their useful lifetime in the face of emerging resistance.”
Skin conditions such as acne, eczema and diabetic ulcers can get infected and develop an armored layer of bacterial cells called a biofilm that is notoriously difficult to defeat. Researchers and doctors have tried a number of physical and chemical methods — including microneedles, heat, sound waves and solvents — for getting past biofilms and the upper layer of skin to the site of deeper infections.
Previous work with ionic liquids showed that some act as antimicrobials, and others can transport drugs through the skin. “It wasn’t obvious that one set of ionic liquids could work against both the barriers,” says study coauthor Samir Mitragotri, a chemical and bioengineer at the University of California, Santa Barbara. The research was published August 25 in the Proceedings of the National Academy of Sciences.
Ionic liquids are made of salts, positively and negatively charged molecules held together by their charge. While the strength of ionic bonds makes most salts — like sodium chloride — solids, the large size of certain molecules lowers the salts’ melting points so they are liquid at room temperature. Ionic liquids are gaining popularity in industries including chemical manufacturing and processing, solar energy and new battery technology.
Mitragotri experimented with a dozen ionic liquids, which he describes as quite viscous, like honey. His group tested how well the liquids killed two different bacterial biofilms, their ability to enhance drug penetration through the skin and whether they cause unwanted damage to skin cells.
The best compound they tested is called choline-geranate. Choline is an essential nutrient and B vitamin, while geranic acid, which forms the ion geranate, is a flavor and fragrance molecule known for its floral and leafy smell.
Choline-geranate completely wiped out the Pseudomonas aeruginosa and Salmonella enterica biofilms in laboratory experiments, Mitragotri and colleagues report. When choline-geranate was mixed with the antibiotic cefadroxil, 16 times as much of the drug penetrated skin, compared with mixing the antibiotic with water. And when the researchers tested the ionic liquid on skin cells, they observed almost no irritation.
The ionic liquids appear to disrupt the polysaccharide-based shell excreted by the bacteria that characterize biofilms, Mitragotri says, but he adds that the exact mechanism isn’t yet clear. His group is already planning more research to understand how ionic liquids disrupt biofilms. At the skin, he speculates that the ionic liquid molecules slip in between the fatty compounds that make up skin cells, creating tiny openings that allow through drugs like cefadroxil.
The researchers’ next steps are to try the choline-geranate and other promising ionic liquids against other bacteria and on infections in living tissue.
Editor's note: This story was updated on August 26, 2014, to correct the description of ionic liquids. Not all ionic liquids are organic.
M. Zakrewsky et al. Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proceedings of the National Academy of Sciences. Published online August 25, 2014. doi: 10.1073/pnas.1403995111.
T.H. Saey. Inside Job. Science News. Vol. 179, June 18, 2011, p. 26.