Microorganisms that are protected in a biofilm pose a significant health risk. Biofilm-protected bacteria account for ~80% of bacterial infections in humans and are 50-1000 times more resistant to antibiotics than their planktonic counterparts. Biofilms on skin are even more concerning due to the increased risk of contact transfer. Our study offers a direct solution to this problem. Ionic liquids (ILs) are increasingly recognized as suitable materials for multiple biological applications. Based upon the tunable nature of ILs, formulations can differ in physicochemical properties by varying both the anionic and cationic component. We report on the use of ILs for biofilm disruption and enhanced antibiotic delivery across skin layers. Each IL in our panel was tested for its ability to disrupt and neutralize the biofilm-forming pathogens, Pseudomonas aeruginosa and Salmonella enterica serovar typhimurium LT2. Further, the same ILs were assayed for cytotoxicity effects on normal bronchial epithelial (NHBE) cells. Finally, the ILs were formulated with the antibiotic cefadroxil, and transdermal drug delivery properties across pig skin evaluated. Multiple ILs in our panel showed promising results in one or more of our assays. However, we identified one IL, choline-geranate, that emerged as the most promising formulation in our panel, as it proved efficacious for pathogen neutralization (106 fold reduction in cell viability), exhibited minimal (&lt;20%) cytotoxic effects on NHBE cells, and had a 20-fold enhancement ratio for drug penetration into skin above a buffered saline control. Data presented will highlight our current efforts in continuing our evaluation of ILs as anti-biofilm agents. We are adopting these methods for application with Gram positive, medically relevant, biofilm-forming bacteria such as MSSA Staphylococcus aureus, in order to demonstrate the broad-spectrum anti-biofilm potential of ionic liquids. Additionally, we are conducting further experiments with antibiotic/IL formulations to assess antibiotic stability and phase transfer kinetics. In summary, these findings provide a foundation for the use of ILs as a topical drug delivery medium in addition to discovering new, effective biofilm-forming pathogen neutralization methods.

Exploiting molten salts for concerted pathogen neutralization and transdermal drug delivery

249th National Meeting (2015)

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