Nitric oxide-loaded chitosan nanoparticles as an innovative antileishmanial platform

Nitric Oxide. 2019 Dec 1:93:25-33. doi: 10.1016/j.niox.2019.09.007. Epub 2019 Sep 18.

Abstract

Leishmaniasis is a neglected tropical disease that demands for new therapeutic strategies due to adverse side effects and resistance development promoted by current drugs. Nitric oxide (NO)-donors show potential to kill Leishmania spp. but their use is limited because of their instability. In this work, we synthesize, characterize, and encapsulate S-nitroso-mercaptosuccinic acid into chitosan nanoparticles (NONPs) and investigate their activity on promastigotes and intracellular amastigotes of Leishmania (Leishmania) amazonensis. Cytotoxicity on macrophages was also evaluated. We verified that NONPs reduced both forms of the parasite in a single treatment. We also noticed reduction of parasitophorous vacuoles as an evidence of inhibition of parasite growth and resolution of infection. No substantial cytotoxicity was detected on macrophages. NONPs were able to provide a sustained parasite killing for both L. (L.) amazonensis infective stages with no toxicity on macrophages, representing a promising nanoplatform for cutaneous leishmaniasis.

Keywords: Bioluminescence; Cutaneous leishmaniasis; Immunofluorescence; Leishmania (L.) amazonensis; Macrophages; S-nitrosothiols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chitosan / chemistry*
  • Chitosan / toxicity
  • Kinetics
  • Leishmania / drug effects*
  • Macrophages / drug effects
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry*
  • Nanoparticles / toxicity
  • Nitric Oxide / chemistry
  • Nitric Oxide Donors / chemistry
  • Nitric Oxide Donors / pharmacology*
  • Nitric Oxide Donors / toxicity
  • Nitroso Compounds / chemistry
  • Nitroso Compounds / pharmacology*
  • Nitroso Compounds / toxicity
  • Thiomalates / chemistry
  • Thiomalates / pharmacology*
  • Thiomalates / toxicity
  • Trypanocidal Agents

Substances

  • Nitric Oxide Donors
  • Nitroso Compounds
  • Thiomalates
  • Trypanocidal Agents
  • Nitric Oxide
  • Chitosan
  • 2-thiomalic acid