A new oral self-emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo

Danielle Sóter do Nascimento Damasio; Patrícia Andrade Antunes; Eduardo Burgarelli Lages; Eliane de Morais-Teixeira; Kátia Duarte Vital; Valbert Nascimento Cardoso; Simone Odılia Antunes Fernandes; Marta Gontijo Aguiar; Lucas Antônio Miranda Ferreira

doi:10.1016/j.ijpharm.2022.122505

A new oral self-emulsifying drug delivery system improves the antileishmania efficacy of fexinidazole in vivo

Int J Pharm. 2023 Jan 25:631:122505. doi: 10.1016/j.ijpharm.2022.122505. Epub 2022 Dec 19.

Authors

Danielle Sóter do Nascimento Damasio¹, Patrícia Andrade Antunes², Eduardo Burgarelli Lages³, Eliane de Morais-Teixeira⁴, Kátia Duarte Vital⁵, Valbert Nascimento Cardoso⁶, Simone Odılia Antunes Fernandes⁷, Marta Gontijo Aguiar⁸, Lucas Antônio Miranda Ferreira⁹

Affiliations

¹ Department of Pharmaceutical Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
² Department of Pharmaceutical Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
³ Department of Pharmaceutical Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
⁴ Clinical Research and Public Policy Group on Infectious and Parasitic Diseases - René Rachou Institute - Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
⁵ Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
⁶ Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
⁷ Department of Clinical and Toxicological Analysis, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
⁸ Department of Pharmaceutical Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].
⁹ Department of Pharmaceutical Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil. Electronic address: [email protected].

PMID: 36549405
DOI: 10.1016/j.ijpharm.2022.122505

Abstract

The aim of this study was to develop, characterize and evaluate the in vivo oral efficacy of self-emulsifying drug delivery systems (SEDDS) containing fexinidazole (FEX) in the experimental treatment of visceral leishmaniasis (VL). The developed FEX-SEDDS formulation presented as a clear, yellowish liquid, with absence of precipitate. The droplet size, polydispersion index and zeta potential after dilution in water (1:200) was of 91 ± 3 nm, 0.242 ± 0.005 and -16.7 ± 0.2, respectively. In the simulated gastric and intestinal media, the FEX-SEDDS had a size of 97 ± 1 and 106 ± 9 nm, respectively. The FEX retention in droplet after SEDDS dilution in simulated gastrointestinal media was almost 100 %. Antileishmanial efficacy studies showed that FEX-SEDDS was the only treatment able to significantly (p < 0.05) reduce the parasite burden in the liver and spleen of animals experimentally infected with Leishmania infantum. Our intestinal permeability data suggest that FEX-SEDDS showed no evidence of injury to the intestinal mucosa. These findings suggest that FEX-SEDDS can be a promising oral alternative for the treatment of VL caused by L. infantum.

Keywords: Fexinidazole; Intestinal permeability; Oral treatment; Self-emulsifying drug release system; Visceral leishmaniasis.

MeSH terms

Administration, Oral
Animals
Antiprotozoal Agents* / pharmacology
Drug Delivery Systems
Emulsifying Agents
Emulsions
Nitroimidazoles*
Solubility

Substances

fexinidazole
Emulsions
Nitroimidazoles
Antiprotozoal Agents
Emulsifying Agents