Development of mannose-anchored thiolated amphotericin B nanocarriers for treatment of visceral leishmaniasis

Nanomedicine (Lond). 2017 Jan;12(2):99-115. doi: 10.2217/nnm-2016-0325. Epub 2016 Nov 23.

Abstract

Aim: Our goal was to improve treatment outcomes for visceral leishmaniasis by designing nanocarriers that improve drug biodistribution and half-life. Thus, long-acting mannose-anchored thiolated chitosan amphotericin B nanocarrier complexes (MTC AmB) were developed and characterized.

Materials & methods: A mannose-anchored thiolated chitosan nanocarrier was manufactured and characterized. MTC AmB was examined for cytotoxicity, biocompatibility, uptake and antimicrobial activities.

Results: MTC AmB was rod shaped with a size of 362 nm. MTC AmB elicited 90% macrophage viability and 71-fold enhancement in drug uptake compared with native drug. The antileishmanial IC50 for MTC AmB was 0.02 μg/ml compared with 0.26 μg/ml for native drug.

Conclusion: These studies show that MTC can serve as a platform for clearance of Leishmania in macrophages.

Keywords: amphotericin B; macrophage nanoparticle targeting; mannose receptors; thiolated chitosan; visceral leishmaniasis.

MeSH terms

  • Amphotericin B / chemistry*
  • Amphotericin B / therapeutic use*
  • Animals
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / therapeutic use
  • Cell Line
  • Chitosan / chemistry
  • Humans
  • Leishmania donovani / drug effects
  • Leishmaniasis, Visceral / drug therapy*
  • Macrophages / drug effects
  • Macrophages / parasitology
  • Mannose / chemistry*
  • Mice
  • Nanoparticles

Substances

  • Antiprotozoal Agents
  • Amphotericin B
  • Chitosan
  • Mannose