Nitric-oxide releasing chitosan nanoparticles towards effective treatment of cutaneous leishmaniasis

Nitric Oxide. 2021 Sep 1:113-114:31-38. doi: 10.1016/j.niox.2021.04.008. Epub 2021 May 1.

Abstract

Cutaneous leishmaniasis (CL) is a major public health problem caused by Leishmania parasites that produce destructive and disfiguring skin conditions. There is an urgent need for alternative topical therapies due to the limitations of current systemic treatments. Recently, we have synthesized nitric oxide-releasing chitosan nanoparticles (NONPs) and shown their potential in vitro against Leishmania amazonensis. Herein we evaluated the application of NONPs for the treatment of CL on infected BALB/c mice. Mice were treated with topical administration of increasing concentrations of NONPs and disease progression was investigated regarding parasite load, lesion thickness, and pain score. As a result, we observed a dose-dependent NONPs effect. Parasite burden and lesion thickness were substantially lower on animals receiving NONPs at a 2 mM concentration compared to untreated control. Moreover, the clinical presentation of the lesions did not show any visible signs of ulcer, suggesting clinical healing in these animals. This successful outcome was sustained for at least 21 days after therapy even in one single dose. Thus, we demonstrate that NONPs are suitable for topical administration, and represent an attractive approach to treat CL.

Keywords: Bioluminescence; Leishmania amazonensis; Lesion thickness; Pain; Parasite burden; S-nitrosothiols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Animals
  • Antiprotozoal Agents / administration & dosage
  • Antiprotozoal Agents / pharmacology*
  • Chitosan / administration & dosage
  • Chitosan / pharmacology*
  • Leishmania / drug effects*
  • Leishmaniasis, Cutaneous / drug therapy*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Cutaneous / pathology
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / pharmacology*
  • Parasitic Sensitivity Tests

Substances

  • Antiprotozoal Agents
  • Nitric Oxide
  • Chitosan