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

Author(s):Show less -

Monteiro, Lis Marie ; Lobenberg, Raimar ; Barbosa, Eduardo Jose ; Barros de Araujo, Gabriel Lima ; Sato, Paula Keiko ; Kanashiro, Edite ; de Araujo Eliodoro, Raissa H. ; Rocha, Mussya ; Teixeira de Freitas, Vera Lucia ; Fotaki, Nikoletta ; Bou-Chacra, Nadia Araci

• Document type: Journal article
• Source: European Journal of Pharmaceutical Sciences; v. 169, p. 11-pg., 2022-02-01.

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 mu M). 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. (AU)

• FAPESP's process: 18/16028-5 - Nanostructured lipid carriers containing buparvaquone applied to the canine leishmaniasis treatment: development, physico-chemical evaluation and in vivo leishmanicidal activity
• Grantee: Lis Marie Monteiro
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE