Emerging Therapeutic Strategies Against Entamoeba Histolytica: Thioredoxin Reductase Inhibition and Nanoparticle-Based Drug Delivery

Abstract

Amoebiasis caused by Entamoeba histolytica is still a clinically important parasitic disease, both intestinal    and    extraintestinal    in   nature, with endemic areas being limited by sanitation and access to molecular diagnosis and treatment especially at lower income countries. Metronidazole and related nitroimidazoles remain essential for invasive disease, their shortcomings include adverse effects, limited activity against luminal cysts, and requirements for a second luminal agent and reduced susceptibility. 

This narrative review highlights the new evidence on novel antiamoebic strategies, focusing on metronidazole resistance, thiol-based redox metabolism, potential drug targets such as thioredoxin reductase, auranofin and related inhibitors, as well as nanoparticle-based delivery.

Using predefined search terms and inclusion/exclusion criteria, a literature review was conducted based on available PubMed, Scopus, Web of Science and Google Scholar using search methodology. Thioredoxin reductase is the most strongly target-based evidence, due to absence of a classical glutathione system in E. histolytica and reliance on thioredoxin-linked pathways for oxidative-stress adaptation. Auranofin provides proof of concept for redox-directed therapy, although resistance adaption toxicity and in vivo efficacy require additional clarification. 

Although work with E. histolytica showed few promising studies supporting nanoparticles, data remains limited in other protozoa and should be regarded as more so supportive than conclusive. Future work should focus on validated models of E. histolytica, host-cell toxicity testing, pharmacokinetic profiling and in vivo studies prior to clinical translation.