When bacteria team up to create biofilms, surrounding themselves in a protective goo, they can cause persistent infections that resist attack from even the most potent antibiotics. Now, chemists have developed self-assembling capsules that can smuggle a payload of peppermint oil and cinnamaldehyde through a biofilm to wipe out the bacteria inside (ACS Nano 2015, DOI: 10.1021/acsnano.5b01696). The researchers, led by Vincent M. Rotello of the University of Massachusetts, Amherst, say that the strategy could offer a way to defeat drug-resistant strains and also promote wound healing.
Biofilms often form around internal medical devices such as urinary catheters and artificial joints, which provide surfaces to colonize. To eliminate the harmful bacteria buried among the polysaccharides, proteins, dead cells, and other detritus that surround them may require treatment with antibiotics at doses thousands of times as high as those used against free bacteria, says Helen E. Blackwell of the University of Wisconsin, Madison, who is also developing ways to disrupt biofilms.
Coating medical devices with silver nitrate or other antibiotic agents can slow biofilm formation. But Rotello decided to look for a way to use inexpensive, toxicologically benign substances to penetrate biofilms that have already formed. Peppermint oil might sound like a meek weapon against such a tough problem, but Rotello points out that its terpene ingredients effectively kill bacteria. Cinnamaldehyde, the compound that gives cinnamon its flavor, is also an effective antimicrobial agent. The main problem is that such essential oils are often insoluble in water, making it difficult to get them in direct contact with bacteria.
Rotello’s solution is to encapsulate droplets of peppermint oil and cinnamaldehyde in a self-assembling shell of silica nanoparticles in water. Each nanoparticle, roughly 150 nm across, carries a dangling amine group that reacts with the cinnamaldehyde to form an imine. The cinnamaldehyde, thus linked to the silica, makes the nanoparticles more hydrophobic and better able to stabilize the 7-µm droplets.
Using fluorescently labeled versions of the silica nanoparticles, the team found that the capsules easily penetrated biofilms of Escherichia coli, perhaps because the cationic silica shells are attracted to negatively charged components in the biofilm, according to Rotello. The biofilm’s acidic environment then broke down the imines, freeing the cinnamaldehyde and peppermint oil.
The researchers tested their miniature grenades on different biofilms formed from three pathogenic strains of bacteria—Pseudomonas aeruginosa, Enterobacter cloacae complex, and a multi-drug-resistant Staphylococcus aureus—and found that the capsules killed at least 99.99% of all the bacteria present. In contrast, unencapsulated peppermint oil had little impact.
In other in vitro tests, the capsules’ cinnamaldehyde seemed to promote the growth of fibroblast cells involved in wound healing. “For me, that’s a major plus,” says Y. S. Prakash, an anesthesiologist and biomedical engineer at the Mayo Clinic in Rochester, Minn. “What you need is something that will kill the biofilm but not the tissue beneath.”
The team does not yet know the precise mechanisms of how the capsules penetrate the biofilm, kill the bacteria, and help fibroblasts. But it clearly works, says Blackwell, adding that it may be possible to smuggle in other therapeutic molecules with the oil droplets.
Rotello, who now hopes to test the capsules in mouse models, says the research demonstrates that common and toxicologically benign compounds can be turned into useful medical tools simply by enhancing their delivery. “Used properly, they can work really well,” he says.