Oral administration of buparvaquone nanostructured lipid carrier enables in vivo activity against Leishmania infantum

Lis Marie Monteiro, Raimar Löbenberg, Eduardo José Barbosa, Gabriel Lima Barros de Araujo, Paula Keiko Sato, Edite Kanashiro, Raissa H. de Araujo Eliodoro, Mussya Rocha, Vera Lúcia Teixeira de Freitas, Nikoletta Fotaki, Nádia Araci Bou-Chacra

Research output: Contribution to journalArticlepeer-review

Abstract

Leishmaniasis, a neglected tropical disease, is prevalent in 98 countries with the occurrence of 1.3 million new cases annually. The conventional therapy for visceral leishmaniasis requires hospitalization due to the severe adverse effects of the drugs, which are administered parenterally. Buparvaquone (BPQ) showed in vitro activity against leishmania parasites; nevertheless, it has failed in vivo tests due to its low aqueous solubility. Though, lipid nanoparticles can overcome this holdback. In this study we tested the hypothesis whether BPQ-NLC shows in vivo activity against L. infantum. Two optimized formulations were prepared (V1: 173.9 ± 1.6 nm, 0.5 mg of BPQ/mL; V2: 232.4 ± 1.6 nm, 1.3 mg of BPQ/mL), both showed increased solubility up to 73.00-fold, and dissolution up to 83.29%, while for the free drug it was only 2.89%. Cytotoxicity test showed their biocompatibility (CC50 >554.4 µM). Besides, the V1 dose of 0.3 mg/kg/day for 10 days reduced the parasite burden in 83.4% ±18.2% (p <0.05) in the liver. BPQ-NLC showed similar leishmanicidal activity compared to miltefosine. Therefore, BPQ-NLC is a promising addition to the limited therapeutic arsenal suitable for leishmaniasis oral administration treatment.

Original languageEnglish
Pages (from-to)106097
Number of pages1
JournalEuropean Journal of Pharmaceutical Sciences
Volume169
Early online date12 Dec 2021
DOIs
Publication statusPublished - 1 Feb 2022

Keywords

  • Buparvaquone
  • Leishmaniasis
  • Nanostructured lipid carrier
  • Neglected diseases

ASJC Scopus subject areas

  • Pharmaceutical Science

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