Efficacy of the treatment using a microemulsion loaded with epoxy-α-lapachone in combination with meglumine antimoniate against murine infection by Leishmania (Leishmania) amazonensis

Int J Parasitol Drugs Drug Resist. 2024 Apr:24:100525. doi: 10.1016/j.ijpddr.2024.100525. Epub 2024 Feb 9.

Abstract

Leishmaniasis is a disease caused by Leishmania spp., affecting millions of people around the world. For decades, its treatment has been based on pentavalent antimonials, which notoriously cause toxic side effects in patients. In this study, epoxy-α-lapachone incorporated into an oil-in-water-type microemulsion (ELAP-ME) and meglumine antimoniate (MA) were assayed in monotherapy and in combination (ELAP-ME/MA) in BALB/c mice infected with Leishmania (Leishmania) amazonensis. In general, there was a reduction in paw lesion size (up to 37% reduction) and decreases of parasite loads in the footpad (∼40%) and lymph nodes (∼31%) of animals treated with ELAP-ME/MA, when compared to the non-treated control groups. Analyses of serum biochemical parameters revealed that the ELAP-ME/MA showed lower renal and hepatic toxicity when compared to MA 2-doses/week monotherapy. These findings indicate that the ELAP-ME/MA combination may be a promising approach for the treatment of cutaneous leishmaniasis.

Keywords: Combination therapy; Cutaneous leishmaniasis treatment; Epoxy-α-lapachone; Glucantime; Leishmania (Leishmania) amazonensis; Meglumine antimoniate; Microemulsion.

MeSH terms

  • Animals
  • Antiprotozoal Agents*
  • Humans
  • Leishmania*
  • Leishmaniasis, Cutaneous* / drug therapy
  • Leishmaniasis, Cutaneous* / parasitology
  • Meglumine / therapeutic use
  • Meglumine Antimoniate / therapeutic use
  • Mice
  • Mice, Inbred BALB C
  • Naphthoquinones*
  • Organometallic Compounds* / therapeutic use

Substances

  • Meglumine Antimoniate
  • alpha-lapachone
  • Antiprotozoal Agents
  • Meglumine
  • Organometallic Compounds
  • Naphthoquinones