Abstract:
PURPOSE:One of the most disturbing trends in recent years is the growth of resistant strains of bacteria with the simultaneous dearth of new antimicrobial agents. Thus, new antimicrobial agents for the use on the ocular surface are needed. METHODS:We synthesized a variety of ionic liquid compounds, which possess 2 positively charged phosphonium groups separated by 10 methylene units in a "bola"-type configuration. We tested these compounds for antimicrobial activity versus a variety of ocular pathogens, as well as their cytoxicity, in vitro in a corneal cell line and in vivo in mice. RESULTS:The ionic liquid Di-Hex C10 demonstrated broad in vitro antimicrobial activity at low micromolar concentrations versus gram-negative and gram-positive organisms, including methicillin-resistant Staphylococcus aureus strains and ocular fungal pathogens. Treatment with Di-Hex C10 resulted in bacterial killing in as little as 15 minutes in vitro. Di-Hex C10 showed little cytotoxicity at 1 μM versus a corneal epithelial cell line or at 10 μM in a mouse corneal wound model. We also show that this bis-phosphonium ionic liquid structure is a key because a comparable monophosphonium ionic liquid is cytotoxic to both bacteria and corneal epithelial cells. CONCLUSIONS:Here, we report the first use of dicationic bis-phosphonium ionic liquids as antimicrobial agents. Our data suggest that diphosphonium ionic liquids may represent a new class of broad-spectrum antimicrobial agents for the use on the ocular surface.
journal_name
Corneajournal_title
Corneaauthors
O'Toole GA,Wathier M,Zegans ME,Shanks RM,Kowalski R,Grinstaff MWdoi
10.1097/ICO.0b013e31823f0a86subject
Has Abstractpub_date
2012-07-01 00:00:00pages
810-6issue
7eissn
0277-3740issn
1536-4798journal_volume
31pub_type
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