Huddled beneath a protective biofilm, bacteria may unleash all manner of mischief. Even better—for the bacteria—their biofilms shelter beneath the outer layer of skin, the stratum corneum, which serves as a natural barrier to most therapeutics. With such double-layered protection, harmful bacteria can become especially dangerous, mainly through enhanced antibiotic resistance, which may rise 50- to 1,000-fold.
Biofilm and skin barriers have been assaulted with bleach and other topical formulations. All too often, however, such agents are effectively rebuffed. Besides, they tend to irritate skin. Finally, they have performed poorly as transdermal drug delivery platforms.
A new line of attack has been proposed by researchers based at Los Alamos National Laboratory and the University of California, Santa Barbara. After a comprehensive search, these researchers identified an “arsenal of materials” known as ionic liquids. According to the researchers, ionic liquids effectively disrupt biofilms, neutralize pathogens, and enhance the delivery of antibiotics into skin.
The scientists published their findings August 25 in the Proceedings of the National Academy of Sciences, in an article entitled, “Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization.”
“In essence, we may have stumbled onto a magic bullet,” said David Fox, Ph.D., a Los Alamos National Laboratory researcher on the project. “In several cases, we found the ionic liquid was more efficacious on a biofilm than a standard bleach treatment and exhibited minimal cytotoxicity effects on human cell lines (unlike bleach). This has excellent prospects for aiding antibiotic delivery to the pathogen through biofilm disruption but, most interestingly, the ionic liquids themselves are quite effective for pathogen neutralization.”
Ionic liquids, which are essentially salts in a liquid state, can be derived from inexpensive, FDA-approved starting materials. Also, ionic liquids are extremely stable to high temperatures and pressures. All of these traits lend ionic liquids to commercialization in real-world applications.
Ionic liquids could help treat chronic wounds and wound degradation, which often result from biofilms. Wounds from infected surgical incisions result in 1 million additional hospital days. Additional causes of bacterial infected wounds include traumatic injuries, as well as diabetic foot ulcers, venous leg ulcers, and pressure ulcers.
Other applications may be explored by the military. “Clearly, the ionic liquids would be of special benefit to our warfighters where exposure to biological agents in hostile environments is likely,” explained Dr. Fox. “Topical application as a prophylaxis or direct treatment to an open wound could buy enough time to reach the proper medical facilities when in an austere environment.”
Of the materials examined by the researchers, choline-geranate emerged as a multipurpose ionic liquid. It showed excellent antimicoribal activity, minimal toxicity to epithelial cells as well as skin, and effective permeation enhancement for drug delivery.
“Choline-geranate was comparable with, or more effective than, bleach treatment against established biofilms of Salmonella enterica and Pseudomonas aeruginosa, respectively,” wrote the authors of the PNAS study. “In addition, choline-geranate increased delivery of cefadroxil, an antibiotic, by >16-fold into the deep tissue layers of the skin without inducing skin irritation.”
The researchers also validated the in vivo efficacy of choline-geranate using a biofilm-infected wound model (>95% bacterial death after two-hour treatment). Such results, the researchers concluded, may establish the use of ionic liquids for simultaneous enhancement of topical drug delivery and antibiotic activity.