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. DelSesto, Andrew T. Koppisch, David T. Fox, Samir Mitragotri

Research output: Contribution to journalArticle

92 Scopus citations

Abstract

Biofilm-protected microbial infections in skin are a serious health risk that remains to be adequately addressed. The lack of progress in developing effective treatment strategies is largely due to the transport barriers posed by the stratum corneum of the skin and the biofilm. In this work, we report on the use of Ionic Liquids (ILs) for biofilm disruption and enhanced antibiotic delivery across skin layers. We outline the syntheses of ILs, analysis of relevant physicochemical properties, and subsequent neutralization effects on two biofilm-forming pathogens: Pseudomonas aeruginosa and Salmonella enterica. Further, the ILs were also examined for cyto-toxicity, skin irritation, delivery of antibiotics through the skin, and treatment of biofilms in a wound model. Of the materials examined, choline-geranate emerged as a multipurpose IL with excellent antimicrobial activity, minimal toxicity to epithelial cells as well as skin, and effective permeation enhancement for drug delivery. Specifically, choline-geranate was comparable with, or more effective than, bleach treatment against established biofilms of S. enterica and P. aeruginosa, respectively. 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 in vivo efficacy of choline-geranate was validated using a biofilm-infected wound model (>95% bacterial death after 2-h treatment). This work establishes the use of ILs for simultaneous enhancement of topical drug delivery and antibiotic activity.

Original languageEnglish (US)
Pages (from-to)13313-13318
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number37
DOIs
StatePublished - Sep 16 2014

Keywords

  • Antibacterial
  • Antibiotic resistance
  • Antimicrobial agents
  • Formulation
  • Ion-pairing

ASJC Scopus subject areas

  • General

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    Zakrewsky, M., Lovejoy, K. S., Kern, T. L., Miller, T. E., Le, V., Nagy, A., Goumas, A. M., Iyer, R. S., DelSesto, R. E., Koppisch, A. T., Fox, D. T., & Mitragotri, S. (2014). Ionic liquids as a class of materials for transdermal delivery and pathogen neutralization. Proceedings of the National Academy of Sciences of the United States of America, 111(37), 13313-13318. https://doi.org/10.1073/pnas.1403995111