Methods: Explant vaginal tissue from estrogenized mice were pre-treated with penicillin-streptomycin and inoculated with 2.5x104 C. albicans or C. glabrata clinical or ATCC isolates and incubated for 24 hours at 37°C to allow for biofilm formation. Thereafter, tissues were treated every 24 hours with vehicle (sterile water), BA 50 mg/mL, or TOL-463 test solutions for up to 3 doses. Fungal burden was assessed by enumeration of CFUs per 500µL of homogenized tissue at 24, 48 and 72 hours after the conclusion of each dose regimen.
Results: TOL-463 was associated with significant reductions in C. albicans and C. glabrata CFUs within 24 hours of the first dose (P < 0.0001). By 72 hours following the third dose, >4 log reductions in CFUs were achieved. Greater inhibition of Candida sp. was demonstrated for TOL-463 compared with BA only by the second dose and the difference was sustained through the final test interval (P < 0.0001).
Conclusion: TOL-463 was highly effective at inhibiting C. albicans and C. glabrata fungal burden/biofilm formation on vaginal mucosa ex vivo that was superior to BA. These findings are consistent with published data for TOL-463 showing the same advantage, with robust destruction of biofilms formed by C. albicans and G. vaginalis in CDC biofilm reactors. An ex vivo study of TOL-463 against G. vaginalis, a key BV pathogen, is ongoing. TOL-463 holds promise as a non-azole vaginal anti-infective with novel antibiofilm properties.
P. Fidel Jr.,
Toltec Pharmaceuticals, LLC: