Mucoadhesive Liposome-Loaded 3,3’-Diindolylmethane Hydrogel: A Potential Formulation for Treatment of Trichomoniasis

Abstract

Trichomoniasis is a sexually transmitted infection caused by the flagellated protozoan Trichomonas vaginalis. 3,3’-Diindolylmethane (DIM) is a bioactive compound with recognized antitumor potential; however, its activity against T. vaginalis remains unexplored. This study aimed to develop and evaluate a topical hydrogel containing DIM-loaded liposomes (HG LIP-DIM) for trichomoniasis treatment. Liposomes (LIP-DIM) were prepared by the lipid film hydration method and incorporated into a 3% guar gum hydrogel. The LIP-DIM was evaluated regarding physicochemical properties, preliminary biocompatibility, in vitro release, antioxidant activity, and anti-T. vaginalis effect. LIP-DIM presented nanoscale characteristics (146 ± 2 nm; PDI 0.17 ± 0.00) and high drug content (85.58 ± 1.21%), with no hemolytic activity compared to free DIM. The system showed controlled release, with less than 50% of the drug released in 12 h, and strong antioxidant activity (92.41 ± 2.01%). Importantly, an 80% reduction in T. vaginalis viability was observed in vitro. The incorporation of LIP-DIM into the hydrogel preserved the physicochemical characteristics of the original dispersion. The HG LIP-DIM was then evaluated for vaginal application performance, demonstrating adequate spreadability, strong mucoadhesion (8218.68 ± 180.19 dyne/cm²), high vaginal retention (98.16 ± 0.33%), and absence of irritation in the HET-CAM assay. Permeation studies confirmed drug retention in the vaginal mucosa without systemic absorption. Overall, the developed liposomal hydrogel combines favorable biopharmaceutical properties with promising in vitro antiparasitic activity, suggesting its potential as a localized vaginal delivery system for DIM. However, these results are preliminary, and further in vivo studies are needed to confirm the safety and therapeutic efficacy of the hydrogel.