Topical treatment of periodontitis using an iongel

Choline and geranic acid (CAGE) ionic liquids inhibit both elastase activity and growth of oral bacteria

“…This concentration is vastly lower than the concentration of CAGE used by Nakajima et al (70% CAGE 1:2 in water, or 1570 mM), 5 and suggests that elastase may be completely inhibited at the concentration used by Nakajima et al Unfortunately, we could not accurately assess the inhibition of elastase at higher concentrations because CAGE undergoes phase changes as the water content increases, becoming viscous at water concentrations above 25%. 5,27 Interestingly, the concentration at which our CAGE formulations began inhibiting elastase was much lower than the concentrations at which Mota et al observed inhibition with their selection of ionic liquids, implying a greater capacity for CAGE-based ionic liquids to inhibit elastase. 20 Additionally, the stoichiometry of CAGE played a role in its inhibition of elastase, with CAGE 1:1 consistently producing less inhibition than its counterparts at concentrations of 5 mM or greater.…”

“…7,8 The remarkable properties of this material make it attractive for application in sites of bacterial infection, and it has recently been reported that CAGE can inhibit periodontitis progression in a rat model. 5 However, while CAGE may be an effective delivery vehicle for small proteins and peptides, like insulin, ionic liquids are generally unsuitable for protein delivery applications due to their tendency to denature proteins. [9][10][11][12][13] While some specific pairings of ionic liquids with (often modified) enzymes have maintained or improved their reaction rate 14,15 or thermal stability, 16 these cases are rare and are rightly considered surprising "given the subtle interplay of chemical and structural features underlying the enzymatic activity, and given its ages-long optimization in a water environment".…”

“…5 They attributed the observed effect to the antimicrobial property of their CAGE formulations, especially against Porphyromonas gingivalis (a pathogen strongly associated with periodontitis). 5 Earlier work has demonstrated that varying the stoichiometry of CAGE ionic liquids impacts their inhibition of bacterial growth 4 and their permeabilization of epithelial barriers. 26 Given the tendency of ionic liquids to denature enzymes and the ability of ionic liquids other than CAGE to inhibit elastase, it is feasible to propose that the observed inhibition of periodontitis progression reported by Nakajima et al is in part due to inhibition of elastase by exposure to CAGE.…”

Advances in Locally Delivered Antimicrobials for Periodontitis Treatment

“…Another therapeutic option is given by deeply eutectic antimicrobial gels, such as choline and geranate gel (CAGE). Nakajima et al demonstrated in a CAGE in vitro and in vivo study deep tissue penetration and antimicrobial activity against P. gingivalis [45].…”

Sustained release of chlorogenic acid-loaded nanomicelles alleviates bone loss in mouse periodontitis

“…Systematic antibiotic therapy can cause bacterial resistance and has disadvantages such as low bioavailability and burst release. [6][7][8] Therefore, it is necessary to find alternative or complementary therapies to reduce the use of antibiotics. In this regard, antioxidant therapy shows great potential for effective treatment of periodontal disease.…”