Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain
Autor(a) principal: | |
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Data de Publicação: | 2023 |
Outros Autores: | , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Brazilian Journal of Pharmaceutical Sciences |
Texto Completo: | https://www.revistas.usp.br/bjps/article/view/212198 |
Resumo: | Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration. |
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Brazilian Journal of Pharmaceutical Sciences |
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Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strainDrug delivery systemsLipid nanoparticlesNanomedicineNeglected diseasesPoorly water-soluble drugsThermal analysisChagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration.Universidade de São Paulo. Faculdade de Ciências Farmacêuticas2023-05-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://www.revistas.usp.br/bjps/article/view/21219810.1590/s2175-97902023e22111Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023); https://doi.org/10.1590/s2175-97902023e22111Brazilian Journal of Pharmaceutical Sciences; v. 59 (2023); https://doi.org/10.1590/s2175-97902023e22111Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023); https://doi.org/10.1590/s2175-97902023e221112175-97901984-8250reponame:Brazilian Journal of Pharmaceutical Sciencesinstname:Universidade de São Paulo (USP)instacron:USPenghttps://www.revistas.usp.br/bjps/article/view/212198/194314https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessda Silva, Flávia Lidiane OliveiraMarques, Maria Betânia de FreitasYoshida, Maria IreneMussel, Wagner da Novada Silveira, João Vinícios WirbitzkiBarroso, Poliana RibeiroKato, Kelly CristinaMartins, HelenCarneiro, Guilherme2023-05-24T17:40:17Zoai:revistas.usp.br:article/212198Revistahttps://www.revistas.usp.br/bjps/indexPUBhttps://old.scielo.br/oai/scielo-oai.phpbjps@usp.br||elizabeth.igne@gmail.com2175-97901984-8250opendoar:2023-05-24T17:40:17Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP)false |
dc.title.none.fl_str_mv |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain |
title |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain |
spellingShingle |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain da Silva, Flávia Lidiane Oliveira Drug delivery systems Lipid nanoparticles Nanomedicine Neglected diseases Poorly water-soluble drugs Thermal analysis |
title_short |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain |
title_full |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain |
title_fullStr |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain |
title_full_unstemmed |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain |
title_sort |
Encapsulation of benznidazole in nanostructured lipid carriers and increased trypanocidal activity in a resistant Trypanosoma cruzi strain |
author |
da Silva, Flávia Lidiane Oliveira |
author_facet |
da Silva, Flávia Lidiane Oliveira Marques, Maria Betânia de Freitas Yoshida, Maria Irene Mussel, Wagner da Nova da Silveira, João Vinícios Wirbitzki Barroso, Poliana Ribeiro Kato, Kelly Cristina Martins, Helen Carneiro, Guilherme |
author_role |
author |
author2 |
Marques, Maria Betânia de Freitas Yoshida, Maria Irene Mussel, Wagner da Nova da Silveira, João Vinícios Wirbitzki Barroso, Poliana Ribeiro Kato, Kelly Cristina Martins, Helen Carneiro, Guilherme |
author2_role |
author author author author author author author author |
dc.contributor.author.fl_str_mv |
da Silva, Flávia Lidiane Oliveira Marques, Maria Betânia de Freitas Yoshida, Maria Irene Mussel, Wagner da Nova da Silveira, João Vinícios Wirbitzki Barroso, Poliana Ribeiro Kato, Kelly Cristina Martins, Helen Carneiro, Guilherme |
dc.subject.por.fl_str_mv |
Drug delivery systems Lipid nanoparticles Nanomedicine Neglected diseases Poorly water-soluble drugs Thermal analysis |
topic |
Drug delivery systems Lipid nanoparticles Nanomedicine Neglected diseases Poorly water-soluble drugs Thermal analysis |
description |
Chagas disease is a neglected parasitic disease caused by Trypanosoma cruzi, whose treatment has remained unsatisfactory for over 50 years, given that it is limited to two drugs. Benznidazole (BZN) is an efficient antichagasic drug used as the first choice, although its poor water-solubility, irregular oral absorption, low efficacy in the chronic phase, and various associated adverse effects are limiting factors for treatment. Incorporating drugs with such characteristics into nanostructured lipid carriers (NLC) is a promising alternative to overcome these limiting obstacles, enhancing drug efficacy and bioavailability while reducing toxicity. Therefore, this study proposed NLC-BZN formulations in different compositions prepared by hot-melt homogenization followed by ultrasound, and the optimized formulation was characterized by FTIR, DRX, DSC, and thermogravimetry. Biological activities included in vitro membrane toxicity (red blood cells), fibroblast cell cytotoxicity, and trypanocidal activity against epimastigotes of the Colombian strain of T. cruzi. The optimized NLC-BZN had a small size (110 nm), negative zeta potential (-18.0 mV), and high encapsulation (1.64% of drug loading), as shown by infrared spectroscopy, X-ray diffraction, and thermal analysis. The NLC-BZN also promoted lower in vitro membrane toxicity (<3% hemolysis), and 50% cytotoxic concentration (CC50) for NLC-BZN in L929 fibroblast cells (110.7 µg/mL) was twice the value as the free BZN (51.3 µg/mL). Our findings showed that the NLC-BZN had higher trypanocidal activity than free BZN against the epimastigotes of the resistant Colombian strain, and this novel NLC-BZN formulation proved to be a promising tool in treating Chagas disease and considered suitable for oral and parenteral administration. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-05-15 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/212198 10.1590/s2175-97902023e22111 |
url |
https://www.revistas.usp.br/bjps/article/view/212198 |
identifier_str_mv |
10.1590/s2175-97902023e22111 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
https://www.revistas.usp.br/bjps/article/view/212198/194314 |
dc.rights.driver.fl_str_mv |
https://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
publisher.none.fl_str_mv |
Universidade de São Paulo. Faculdade de Ciências Farmacêuticas |
dc.source.none.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023); https://doi.org/10.1590/s2175-97902023e22111 Brazilian Journal of Pharmaceutical Sciences; v. 59 (2023); https://doi.org/10.1590/s2175-97902023e22111 Brazilian Journal of Pharmaceutical Sciences; Vol. 59 (2023); https://doi.org/10.1590/s2175-97902023e22111 2175-9790 1984-8250 reponame:Brazilian Journal of Pharmaceutical Sciences instname:Universidade de São Paulo (USP) instacron:USP |
instname_str |
Universidade de São Paulo (USP) |
instacron_str |
USP |
institution |
USP |
reponame_str |
Brazilian Journal of Pharmaceutical Sciences |
collection |
Brazilian Journal of Pharmaceutical Sciences |
repository.name.fl_str_mv |
Brazilian Journal of Pharmaceutical Sciences - Universidade de São Paulo (USP) |
repository.mail.fl_str_mv |
bjps@usp.br||elizabeth.igne@gmail.com |
_version_ |
1800222918099075072 |