New Ionic Liquids May Disrupt Pathogenic Biofilms, Enhance Antibiotic Delivery Interview with:
David T. Fox, Ph.D. Scientist 3 Los Alamos National Laboratory andDavid T. Fox, Ph.D.
Scientist 3
Los Alamos National Laboratory and
Prof. Samir Mitragotri Center for Bioengineering and Department of Chemical Engineering University of California, Santa Barbara, CA 93106Prof. Samir Mitragotri
Center for Bioengineering and Department of Chemical Engineering
University of California, Santa Barbara, CA 93106

Medical Research: What are the main findings of this study?

Answer: Our research team identified a molten salt, choline-geranate, that possessed multiple beneficial biological traits. Specifically, when mixed in a 1:2 ratio (choline:geranate) this solvent is able to effectively disrupt and neutralize 72-hour biofilms formed by both Pseudomonas aeruginosa and Salmonella enterica. Further, our studies demonstrated the same solvent exhibited minimal cytotoxicity effects to normal human bronchial epithelial (NHBE) cells and was able to deliver an antibiotic, cefadroxil, through the stratum corneum into the epidermis and dermis. Most importantly, the research culminated in demonstrating the molten salt was able to neutralize ~95% of the bacteria found within a 24-hour P. aeruginosa biofilm when grown on a skin wound model (MatTek)  and ~98% of the bacteria when formulated with the antibiotic, ceftazidime. When the biofilm was treated with only antibiotic in a saline solution, less than 20% of the bacteria were neutralized.

Medical Research: Were any of the findings surprising?

Answer: The most surprising finding was the observation the neat ionic liquids were quite effective antimicrobial agents in the absence of the antibiotic. We built a hypothesis that the ionic liquids would serve as a carrier of the antibiotic either to the bacteria or for facile penetration through the skin for subsequent antibiotic delivery. This was a serendipitous finding that ultimately opened the door for use of molten salts as both a standalone therapy and as a formulation with broad-spectrum antibiotics. Further, some of the ionic liquids were more effective than a 10% bleach solution on the microbes tested when applied for the same period of time yet did not exhibit the prototypical cytotoxicity effects that bleach had on the cell lines tested.

Medical Research: What should patients and clinicians take away from this report?

Answer: Clinicians and patients should embrace the potential for reexamining previously discarded antibiotics due to either poor bioavailability or where antibiotic resistance was observed. In addition, there is potential a new arsenal of therapeutic agents was added to an ever shrinking repertoire of current effective treatments on resilient bacteria both on the surface of skin and the underlying tissue layers.

Medical Research: What future research do you suggest as a result of this study?

Answer: Two major routes of future research should be undertaken in order to further develop use of this class of materials in a clinical setting.

First, a more exhaustive set of pathogens (both Gram positive and Gram negative) need to be examined in order to assess the broad-spectrum ability of the ionic liquids for pathogen neutralization in conjunction with the molecular mechanism for biofilm disruption and/or skin penetration.

The second, a more immediate, direction is to translate this research to in vivo studies to assess the effect of ionic liquids and their antibiotic formulations on the treatment of open wounds.


Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization

Michael Zakrewsky, Katherine S. Lovejoy, Theresa L. Kern, Tarryn E. Miller, Vivian Le, Amber Nagy, Andrew M. Goumas, Rashi S. Iyer, Rico E. Del Sesto, Andrew T. Koppisch, David T. Fox, and Samir Mitragotri

PNAS 2014 ; published ahead of print August 25, 2014, doi:10.1073/pnas.1403995111