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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 37; pp. 13313 - 13318
• Main Authors: Zakrewsky, Michael, Lovejoy, Katherine S., Kern, Theresa L., Miller, Tarryn E., Le, Vivian, Nagy, Amber, Goumas, Andrew M., Iyer, Rashi S., Del Sesto, Rico E., Koppisch, Andrew T., Fox, David T., Mitragotri, Samir
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16.09.2014; National Acad Sciences
• Subjects: Administration, Cutaneous; Antibacterials; Antibiotics; Biofilms; Biofilms - drug effects; Biological Sciences; Cell Death - drug effects; Cytotoxicity; Drug Delivery Systems; Epithelial Cells - cytology; Epithelial Cells - drug effects; Humans; Ionic liquids; Ionic Liquids - pharmacology; Ions; Irritants - toxicity; Irritation; Liquids; Microbial Sensitivity Tests; Pathogens; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - physiology; Reproducibility of Results; Salmonella enterica; Salmonella enterica - drug effects; Salmonella enterica - physiology; Skin; Skin - drug effects; Skin irritation; Skin, Artificial - microbiology; Spectroscopy, Fourier Transform Infrared; Transdermal application; formulation; antibacterial; antimicrobial agents; ion-pairing; antibiotic resistance
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1403995111

Significance Effective treatment of skin-based bacterial biofilms has been identified as a serious and unmet medical need. Biofilm-protected bacteria account for ∼80% of bacterial infections in humans and are 50–1,000 times more resistant to antibiotics than their planktonic counterparts. Biofilms in skin are further protected by the outermost layer of skin, the stratum corneum, which serves as a natural barrier to most therapeutics. Here, we present compelling evidence for exploiting ionic liquids (ILs) as an arsenal of materials both in a concerted effort to combat antibiotic-resistant bacterial biofilms in skin as well as for topical transdermal drug delivery. Our comprehensive strategy resulted in the identification of ILs that are effective at disrupting biofilms, neutralizing pathogens, and enhancing delivery of antibiotic into skin. Moreover, ILs did not show skin irritation that is typically associated with topical formulations.