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

doi:10.1016/j.ejps.2021.106097

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 journal › Article › peer-review

8 Citations (SciVal)

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 language	English
Pages (from-to)	106097
Number of pages	1
Journal	European Journal of Pharmaceutical Sciences
Volume	169
Early online date	12 Dec 2021
DOIs	https://doi.org/10.1016/j.ejps.2021.106097
Publication status	Published - 1 Feb 2022

Funding

This study was supported by the São Paulo Research Support Foundation (FAPESP) grant 2018/16028-5 . This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) - Finance Code 001. The paper was revised by Jim Hesson (http://academicenglishsolutions.com/AES/home.html). This study was supported by the S?o Paulo Research Support Foundation (FAPESP) grant 2018/16028-5. This study was financed in part by the Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior ? Brazil (CAPES) - Finance Code 001. The paper was revised by Jim Hesson (http://academicenglishsolutions.com/AES/home.html).

Keywords

Buparvaquone
Leishmaniasis
Nanostructured lipid carrier
Neglected diseases

ASJC Scopus subject areas

Pharmaceutical Science

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ejps.2021.106097Licence: CC BY-NC-ND

Cite this

Monteiro, L. M., Löbenberg, R., Barbosa, E. J., de Araujo, G. L. B., Sato, P. K., Kanashiro, E., de Araujo Eliodoro, R. H., Rocha, M., de Freitas, V. L. T., Fotaki, N., & Bou-Chacra, N. A. (2022). Oral administration of buparvaquone nanostructured lipid carrier enables in vivo activity against Leishmania infantum. European Journal of Pharmaceutical Sciences , 169, 106097. https://doi.org/10.1016/j.ejps.2021.106097

Monteiro, LM, Löbenberg, R, Barbosa, EJ, de Araujo, GLB, Sato, PK, Kanashiro, E, de Araujo Eliodoro, RH, Rocha, M, de Freitas, VLT, Fotaki, N & Bou-Chacra, NA 2022, 'Oral administration of buparvaquone nanostructured lipid carrier enables in vivo activity against Leishmania infantum', European Journal of Pharmaceutical Sciences , vol. 169, pp. 106097. https://doi.org/10.1016/j.ejps.2021.106097

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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.",

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AU - Monteiro, Lis Marie

AU - Löbenberg, Raimar

AU - Barbosa, Eduardo José

AU - de Araujo, Gabriel Lima Barros

AU - Sato, Paula Keiko

AU - Kanashiro, Edite

AU - de Araujo Eliodoro, Raissa H.

AU - Rocha, Mussya

AU - de Freitas, Vera Lúcia Teixeira

AU - Fotaki, Nikoletta

AU - Bou-Chacra, Nádia Araci

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ER -

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

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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Cite this

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

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Zetasizer

Cite this