Increased body exposure to new anti-trypanosomal through nanoencapsulation.
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/handle/123456789/11016 |
Resumo: | Lychnopholide, a lipophilic sesquiterpene lactone, is efficacious in mice at the acute and chronic phases of Chagas disease. Conventional poly-ε-caprolactone (PCL) and long-circulating poly(D,L-lactide)-block-polyethylene glycol (PLA-PEG) nanocapsules containing lychnopholide were developed and characterized. Lychnopholide presented high association efficiency (>90%) with the nanocapsules. A new, fast and simple HPLC-UV-based bioanalytical method was developed, validated in mouse plasma and applied to lychnopholide quantification in in vitro release kinetics and pharmacokinetics. The nanocapsules had mean hydrodynamic diameters in the range of 100–250 nm, negative zeta potentials (−30 mV to −57 mV), with good physical stability under storage. Atomic force microscopy morphological analysis revealed spherical monodispersed particles and the absence of lychnopholide crystallization or aggregation. Association of lychnopholide to PLA-PEG nanocapsules resulted in a 16-fold increase in body exposure, a 26-fold increase in plasma half-life and a dramatic reduction of the lychnopholide plasma clearance (17-fold) in comparison with free lychnopholide. The improved pharmacokinetic profile of lychnopholide in long-circulating nanocapsules is in agreement with the previously reported improved efficacy observed in Trypanosoma cruzi-infected mice. The present lychnopholide intravenous dosage form showed great potential for further pre-clinical and clinical studies in Chagas disease and cancer therapies. |
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Branquinho, Renata TupinambáLana, Gwenaelle Elza Nathalie PoundMilagre, Matheus MarquesGuimarães, Dênia Antunes SaúdeVilela, José Mário CarneiroAndrade, Margareth SpanglerLana, Marta deMosqueira, Vanessa Carla Furtado2019-04-15T14:34:15Z2019-04-15T14:34:15Z2017BRANQUINHO, R. T. et al. Increased body exposure to new anti-trypanosomal through nanoencapsulation. Scientific Reports, v. 7, p. 1-12, 2017. Disponível em: <https://www.nature.com/articles/s41598-017-08469-x>. Acesso em: 25 fev. 2019.20452322http://www.repositorio.ufop.br/handle/123456789/11016Lychnopholide, a lipophilic sesquiterpene lactone, is efficacious in mice at the acute and chronic phases of Chagas disease. Conventional poly-ε-caprolactone (PCL) and long-circulating poly(D,L-lactide)-block-polyethylene glycol (PLA-PEG) nanocapsules containing lychnopholide were developed and characterized. Lychnopholide presented high association efficiency (>90%) with the nanocapsules. A new, fast and simple HPLC-UV-based bioanalytical method was developed, validated in mouse plasma and applied to lychnopholide quantification in in vitro release kinetics and pharmacokinetics. The nanocapsules had mean hydrodynamic diameters in the range of 100–250 nm, negative zeta potentials (−30 mV to −57 mV), with good physical stability under storage. Atomic force microscopy morphological analysis revealed spherical monodispersed particles and the absence of lychnopholide crystallization or aggregation. Association of lychnopholide to PLA-PEG nanocapsules resulted in a 16-fold increase in body exposure, a 26-fold increase in plasma half-life and a dramatic reduction of the lychnopholide plasma clearance (17-fold) in comparison with free lychnopholide. The improved pharmacokinetic profile of lychnopholide in long-circulating nanocapsules is in agreement with the previously reported improved efficacy observed in Trypanosoma cruzi-infected mice. The present lychnopholide intravenous dosage form showed great potential for further pre-clinical and clinical studies in Chagas disease and cancer therapies.This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Fonte: o próprio artigoinfo:eu-repo/semantics/openAccessIncreased body exposure to new anti-trypanosomal through nanoencapsulation.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOPLICENSElicense.txtlicense.txttext/plain; charset=utf-8924http://www.repositorio.ufop.br/bitstream/123456789/11016/2/license.txt62604f8d955274beb56c80ce1ee5dcaeMD52ORIGINALARTIGO_IncreasedBodyExposure.pdfARTIGO_IncreasedBodyExposure.pdfapplication/pdf2161439http://www.repositorio.ufop.br/bitstream/123456789/11016/1/ARTIGO_IncreasedBodyExposure.pdf35dc82a375825ca21ac712f1355b41eaMD51123456789/110162019-04-15 10:34:15.122oai:localhost: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ório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332019-04-15T14:34:15Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.pt_BR.fl_str_mv |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. |
title |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. |
spellingShingle |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. Branquinho, Renata Tupinambá |
title_short |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. |
title_full |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. |
title_fullStr |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. |
title_full_unstemmed |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. |
title_sort |
Increased body exposure to new anti-trypanosomal through nanoencapsulation. |
author |
Branquinho, Renata Tupinambá |
author_facet |
Branquinho, Renata Tupinambá Lana, Gwenaelle Elza Nathalie Pound Milagre, Matheus Marques Guimarães, Dênia Antunes Saúde Vilela, José Mário Carneiro Andrade, Margareth Spangler Lana, Marta de Mosqueira, Vanessa Carla Furtado |
author_role |
author |
author2 |
Lana, Gwenaelle Elza Nathalie Pound Milagre, Matheus Marques Guimarães, Dênia Antunes Saúde Vilela, José Mário Carneiro Andrade, Margareth Spangler Lana, Marta de Mosqueira, Vanessa Carla Furtado |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Branquinho, Renata Tupinambá Lana, Gwenaelle Elza Nathalie Pound Milagre, Matheus Marques Guimarães, Dênia Antunes Saúde Vilela, José Mário Carneiro Andrade, Margareth Spangler Lana, Marta de Mosqueira, Vanessa Carla Furtado |
description |
Lychnopholide, a lipophilic sesquiterpene lactone, is efficacious in mice at the acute and chronic phases of Chagas disease. Conventional poly-ε-caprolactone (PCL) and long-circulating poly(D,L-lactide)-block-polyethylene glycol (PLA-PEG) nanocapsules containing lychnopholide were developed and characterized. Lychnopholide presented high association efficiency (>90%) with the nanocapsules. A new, fast and simple HPLC-UV-based bioanalytical method was developed, validated in mouse plasma and applied to lychnopholide quantification in in vitro release kinetics and pharmacokinetics. The nanocapsules had mean hydrodynamic diameters in the range of 100–250 nm, negative zeta potentials (−30 mV to −57 mV), with good physical stability under storage. Atomic force microscopy morphological analysis revealed spherical monodispersed particles and the absence of lychnopholide crystallization or aggregation. Association of lychnopholide to PLA-PEG nanocapsules resulted in a 16-fold increase in body exposure, a 26-fold increase in plasma half-life and a dramatic reduction of the lychnopholide plasma clearance (17-fold) in comparison with free lychnopholide. The improved pharmacokinetic profile of lychnopholide in long-circulating nanocapsules is in agreement with the previously reported improved efficacy observed in Trypanosoma cruzi-infected mice. The present lychnopholide intravenous dosage form showed great potential for further pre-clinical and clinical studies in Chagas disease and cancer therapies. |
publishDate |
2017 |
dc.date.issued.fl_str_mv |
2017 |
dc.date.accessioned.fl_str_mv |
2019-04-15T14:34:15Z |
dc.date.available.fl_str_mv |
2019-04-15T14:34:15Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
BRANQUINHO, R. T. et al. Increased body exposure to new anti-trypanosomal through nanoencapsulation. Scientific Reports, v. 7, p. 1-12, 2017. Disponível em: <https://www.nature.com/articles/s41598-017-08469-x>. Acesso em: 25 fev. 2019. |
dc.identifier.uri.fl_str_mv |
http://www.repositorio.ufop.br/handle/123456789/11016 |
dc.identifier.issn.none.fl_str_mv |
20452322 |
identifier_str_mv |
BRANQUINHO, R. T. et al. Increased body exposure to new anti-trypanosomal through nanoencapsulation. Scientific Reports, v. 7, p. 1-12, 2017. Disponível em: <https://www.nature.com/articles/s41598-017-08469-x>. Acesso em: 25 fev. 2019. 20452322 |
url |
http://www.repositorio.ufop.br/handle/123456789/11016 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
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reponame:Repositório Institucional da UFOP instname:Universidade Federal de Ouro Preto (UFOP) instacron:UFOP |
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UFOP |
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Repositório Institucional da UFOP |
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