Benznidazole-Loaded Polymeric Nanoparticles for Oral Chemotherapeutic Treatment of Chagas Disease

Author:

Sousa Lucas Resende Dutra1ORCID,Duarte Thays Helena Chaves2,Xavier Viviane Flores1,das Mercês Aline Coelho2,Vieira Gabriel Maia3ORCID,Martins Maximiliano Delany3ORCID,Carneiro Cláudia Martins4ORCID,dos Santos Viviane Martins Rebello5ORCID,dos Santos Orlando David Henrique1ORCID,Vieira Paula Melo de Abreu2ORCID

Affiliation:

1. Laboratório de Fitotecnologia, Programa de Pós-Graduação em Ciências Farmacêuticas, Escola de Farmácia, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil

2. Laboratório de Morfopatologia, Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil

3. Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte 31270-901, MG, Brazil

4. Laboratório de Imunopatologia, Programa de Pós-Graduação em Ciências Biológicas, Núcleo de Pesquisas em Ciências Biológicas, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil

5. Laboratório de Produtos Naturais e de Síntese Orgânica, Programa de Pós-Graduação em Química, Instituto de Ciências Exatas e Biológicas, Universidade Federal de Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto 35400-000, MG, Brazil

Abstract

Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate systems containing BZ is therefore being promoted. The objective of this investigation was to develop polymeric nanoparticles loaded with BZ and examine their trypanocidal impact in vitro. Two formulas (BNP1 and BNP2) were produced through double emulsification and freeze drying. Subsequent to physicochemical and morphological assessment, both formulations exhibited adequate yield, average particle diameter, and zeta potential for oral administration. Cell viability was assessed in H9C2 and RAW 264.7 cells in vitro, revealing no cytotoxicity in cardiomyocytes or detrimental effects in macrophages at specific concentrations. BNP1 and BNP2 enhanced the effect of BZ within 48 h using a treatment of 3.90 μg/mL. The formulations notably improved NO reduction, particularly BNP2. The findings imply that the compositions are suitable for preclinical research, underscoring their potential as substitutes for treating CD. This study aids the quest for new BZ formulations, which are essential in light of the disregard for the treatment of CD and the unfavorable effects associated with its commercial product.

Publisher

MDPI AG

Reference100 articles.

1. American Public Health Association (2022). Factsheet: Chagas Disease in the Americas for Public Health Workers.

2. World Health Organization (2013). Sustaining the Drive to Overcome the Global Impact of Neglected Tropical Diseases: Second WHO Report on Neglected Diseases.

3. World Health Organization (2023). Menos de 10% das Pessoas com Doença de Chagas Recebem um Diagnóstico.

4. Chagas disease: 100 years after its discovery. A systemic review;Coura;Acta Trop.,2010

5. A critical review on Chagas disease chemotherapy;Mem. Inst. Oswaldo Cruz,2002

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