Polycaprolactone Antimony Nanoparticles as Drug Delivery System for Leishmaniasis

Am J Ther. 2019 Jan/Feb;26(1):e12-e17. doi: 10.1097/MJT.0000000000000539.

Abstract

Background: Leishmaniasis is a neglected disease endemic in tropical and subtropical areas, with an incidence about 1.6 million cases/year. The first-line treatment of this disease is pentavalent antimony, and the second-line are pentamidine and amphotericin B. All the treatments available cause severe side effects and often have difficulty in accessing parasites within infected cells.

Study question: This study aimed to determine if the use of nanoparticles loaded with meglumine antimoniate could reach and targeting infected organs with leishmaniasis, reducing the dosage used and promoting less adverse effects.

Study design: This study was performed comparing the meglumine nanoparticle in two experimental groups. The first one healthy mice and the second one inducted mice (leishmaniasis).

Measures and outcomes: The nanoparticles loaded with meglumine antimoniate (nanoantimony) were prepared by double-emulsion solvent evaporation method and showed a size of about 150-200 nm. BALB/c mice infected or not with Leishmania amazonensis (cutaneous leishmaniasis model) or Leishmania infantum (visceral leishmaniasis model) was used to access the biodistribution of nanoantimony and meglumine antimoniate labeled with technetium-99m.

Results: The biodistribution profiles showed a preferential targeting of the nanoparticles to the liver, spleen, and lungs. Because these are the main organs infected, the nanoparticle may be used for this purpose. The results for cutaneous leishmaniasis showed a low uptake by the lesion (infected region).

Conclusions: The results demonstrated the potential use of these nanoparticles to improve the efficacy of meglumine antimoniate in the treatment of visceral leishmaniasis, indicating their potential as an alternative therapeutic strategy for leishmaniasis infections.

MeSH terms

  • Animals
  • Antiprotozoal Agents / administration & dosage*
  • Disease Models, Animal
  • Drug Delivery Systems / methods*
  • Humans
  • Leishmania infantum / pathogenicity
  • Leishmania mexicana / pathogenicity
  • Leishmaniasis, Cutaneous / drug therapy*
  • Leishmaniasis, Cutaneous / parasitology
  • Leishmaniasis, Visceral / drug therapy*
  • Leishmaniasis, Visceral / parasitology
  • Meglumine Antimoniate / administration & dosage*
  • Meglumine Antimoniate / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / chemistry
  • Polyesters / chemistry
  • Technetium / chemistry
  • Tissue Distribution
  • Treatment Outcome

Substances

  • Antiprotozoal Agents
  • Polyesters
  • Technetium-99
  • polycaprolactone
  • Technetium
  • Meglumine Antimoniate