Critical Antileishmanial in vitro Effects of Highly Examined Gold Nanoparticles

Int J Nanomedicine. 2021 Oct 28:16:7285-7295. doi: 10.2147/IJN.S268548. eCollection 2021.

Abstract

Introduction: The current therapeutic armory for visceral leishmaniasis (VL) caused by Leishmania donovani complex is inadequate, coupled with serious limitations. Combination therapy has proved ineffective due to mounting resistance; however, the search for safe and effective drugs is desirable, in the absence of any vaccine. There is a growing interest in the application of nanoparticles for the therapeutic effectiveness of leishmaniasis. Aimed in this direction, we assessed the antileishmanial effect of gold nanoparticles (GNP) against L. donovani in vitro.

Methods: GNP were synthesized and characterized for particle size by dynamic light scattering (DLS) and atomic force microscopy (AFM) and for optical properties by UV-visible spectroscopy. Cytotoxicity of GNP was measured by the MTT proliferation assay. The antileishmanial activity of the nanoparticles was evaluated against L. donovani promastigotes and macrophage-infected amastigotes in vitro.

Results: GNP showed a strong SPR peak at 520 nm and mean particle size, polydispersity index (PDI), and zeta potential of 56.0 ± 10 nm, 0.3 ± 0.1 and -27.0 ± 3 mV, respectively. The GNPs were smooth and spherical with a mean particle diameter of 20 ± 5 nm. Nanoparticles [1.2-100 µM] did not reveal any cytotoxicity on RAW 264.7 murine macrophage cell line, but exerted significant activity against both promastigotes and amastigote stages of L. donovani with 50% inhibitory concentrations (IC50) of 18.4 ± 0.4 µM and 5.0 ± 0.3 µM, respectively. GNP showed significant antileishmanial activity with deformed morphology of parasites and the least number of surviving promastigotes after growth reversibility analysis.

Conclusion: GNP may provide a platform to conjugate antileishmanial drugs onto the surface of nanoparticles to enhance their therapeutic effectiveness against VL. Further work is warranted, involving more in-depth mechanistic studies and in vivo investigations.

Keywords: amastigotes; gold nanoparticles; promastigotes; surface plasmon resonance; visceral leishmaniasis L. donovani.

MeSH terms

  • Animals
  • Antiprotozoal Agents* / pharmacology
  • Antiprotozoal Agents* / therapeutic use
  • Gold / therapeutic use
  • Leishmania donovani*
  • Leishmaniasis, Visceral* / drug therapy
  • Metal Nanoparticles*
  • Mice
  • Pharmaceutical Preparations*

Substances

  • Antiprotozoal Agents
  • Pharmaceutical Preparations
  • Gold