Composite Thermoresponsive Hydrogel with Auranofin‐Loaded Nanoparticles for Topical Treatment of Vaginal Trichomonad Infection

Abstract

Trichomonas vaginalis is responsible for the most common non‐viral sexually transmitted disease worldwide. Standard treatment is with oral metronidazole or tinidazole, but resistance is emerging and adverse effects can be problematic. Topical treatment offers potential benefits for increasing local drug concentrations while reducing systemic exposure, but none are currently approved for trichomoniasis. The anti‐rheumatic drug, auranofin (AF), was recently discovered to have significant trichomonacidal activity, but has a long plasma half‐life and significant adverse effects. Here, this drug is used as a model to develop a novel topical formulation composed of AF‐loaded nanoparticles (NP) embedded in a thermoresponsive hydrogel for intravaginal administration. The AF‐NP composite gel shows sustained drug release for at least 12 h, and underwent sol–gel transition with increased viscoelasticity within a minute. Intravaginal administration in mice shows excellent NP retention for >6 h and markedly increases local AF levels, but reduces plasma and liver levels compared to oral treatment with a much higher dose. Furthermore, intravaginal AF‐NP gel greatly outperforms oral AF in eliminating vaginal trichomonad infection in mice, while causing no systemic or local toxicity. These results show the potential of the AF‐NP hydrogel formulation for effective topical therapy of vaginal infections.