Secnidazole and metronidazole in the treatment of Trichomoniasis: Comparative study of the mechanism of action and development of innovative 3D printed intrauterine devices.

Trichomonas vaginalis is the causative agent of trichomoniasis, the most prevalent non-viral sexually transmitted infection (STI) worldwide. This study aimed to evaluate the susceptibility of five T. vaginalis isolates to secnidazole and metronidazole - two of the three FDA-approved treatments. We also investigated their mechanisms of action and explored the use of 3D printing technology for delivering anti-T. vaginalis therapy. In vitro susceptibility assays were performed using secnidazole and metronidazole. To investigate their mechanisms of action, we assessed reactive oxygen and nitrogen species (ROS/RNS) production, lipid peroxidation, type of cell death, and superoxide dismutase (SOD) gene expression by qRT-PCR. DNA integrity was evaluated using the comet assay. Additionally, we designed 3D-printed intrauterine devices (IUDs) loaded with each drug to evaluate their efficacy in eradicating T. vaginalis. All isolates were more susceptible to secnidazole than to metronidazole. Neither drug increased ROS/RNS levels or lipid peroxidation. However, both downregulated SOD expression in most isolates and induced apoptosis-like cell death, evidenced by phosphatidylserine exposure. No DNA strand breaks were detected. Drug-loaded 3D-printed IUDs eradicated T. vaginalis trophozoites within 24 h, with secnidazole achieving this effect as early as 10 h post-treatment. Secnidazole and metronidazole appear to disrupt redox homeostasis through a mechanism independent of ROS/RNS, likely by downregulating SOD and increasing cellular susceptibility to oxidative stress. Both drugs induced apoptosis-like cell death without causing DNA damage. The drug-loaded devices represent a promising strategy for localized and personalized treatment. This is the first proof-of-concept for a 3D-printed IUD loaded with secnidazole and metronidazole demonstrating trichomonacidal action and highlighting a novel, localized drug delivery strategy with potential applications in personalized medicine for the treatment of trichomoniasis.