(162a) Topical Application of Choline-Based Ionic Liquid (CAGE) to the Treatment of Oral Infectious Disease

To overcome the difficulty of topical drug delivery to the oral mucosa for treatment of periodontitis, we assessed the efficacy of choline and geranic acid based ionic liquids (CAGE) that greatly enhanced transdermal delivery ¹. Ten ul of 3 kinds of solutions of 1:2 (choline : geranic acid) CAGE (100, 70 and 50 % v/v) were applied on the center of palate or around the upper anterior teeth of wistar rats for 10 minutes. Then the permeability of the solutions into the gingival tissues and the gingival sulcus, where the periodontal pathogen mainly exist, were evaluated by Ultra High Performance Liquid Chromatography/Mass Spectrometer (UPLC/MS). Subsequently, Minimal Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), and time-dependent antimicrobial activity of 1:2 CAGE against Porphyromonas gingivalis W83, which is the major periodontopathic bacteria, were determined. After the treatment of mature biofilm with 1:2 CAGE, biomass was quantified using crystal violet (CV) staining, and the biofilm was observed by Scanning Electron Microscopy (SEM). After the administration of 70 % solution, increasing of the concentrations of CAGE were observed in the gingival dermal layer (>5 ug/ul) for 15 min and the sulcus (>10 ug/ul) for 30 min. The MIC and MBC was 1.2 and 4.7 ug/ul, respectively. Two fold of MBC (9.4 ug/ul) killed the bacteria completely within 15 min, and reduce biomass of the biofilm. The destruction of the biofilm was observed by SEM. Overall, high enough concentration of 1:2 CAGE was detected for long enough time to eliminate the pathogen/biofilm in the gingival and sulcus. This work demonstrated the significant capacity of 1:2 CAGE as an novel application to periodontal therapy.

1. Tanner, E.E.L. et al. Design Principles of Ionic Liquids for Transdermal Drug Delivery. Adv Mater, e1901103 (2019).