Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity.
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFOP |
Texto Completo: | http://www.repositorio.ufop.br/handle/123456789/6627 https://doi.org/10.1002/jps.24569 |
Resumo: | In this study, the methotrexate (MTX) was incorporated into the poly(-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-_ and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile. C _ 2015Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. |
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Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity.Biodegradable polymersBiomaterialsControlled release/deliveryTargeted drug deliveryPolymeric drug delivery systemsIn this study, the methotrexate (MTX) was incorporated into the poly(-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-_ and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile. C _ 2015Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.2016-07-25T16:21:12Z2016-07-25T16:21:12Z2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfOLIVEIRA, L. G. de et al. Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. Journal of Pharmaceutical Sciences, v. 104, p. 3731-3742, 2015. Disponível em: <http://www.sciencedirect.com/science/article/pii/S0022354916301599>. Acesso em: 16 jun. 2016.1520-6017http://www.repositorio.ufop.br/handle/123456789/6627https://doi.org/10.1002/jps.24569O periódico Journal of Pharmaceutical Sciences concede permissão para depósito deste artigo no Repositório Institucional da UFOP. Número da licença: 3897040971930.info:eu-repo/semantics/openAccessOliveira, Leandro Gonzaga deFigueiredo, Letícia AparecidaCunha, Gabriella Maria FernandesOliveira, Laser Antônio Machado deMiranda, Marina Barcelos deSilva, Gisele Rodrigues daMoura, Sandra Aparecida Lima deengreponame:Repositório Institucional da UFOPinstname:Universidade Federal de Ouro Preto (UFOP)instacron:UFOP2019-09-20T14:51:58Zoai:repositorio.ufop.br:123456789/6627Repositório InstitucionalPUBhttp://www.repositorio.ufop.br/oai/requestrepositorio@ufop.edu.bropendoar:32332019-09-20T14:51:58Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP)false |
dc.title.none.fl_str_mv |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. |
title |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. |
spellingShingle |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. Oliveira, Leandro Gonzaga de Biodegradable polymers Biomaterials Controlled release/delivery Targeted drug delivery Polymeric drug delivery systems |
title_short |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. |
title_full |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. |
title_fullStr |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. |
title_full_unstemmed |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. |
title_sort |
Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. |
author |
Oliveira, Leandro Gonzaga de |
author_facet |
Oliveira, Leandro Gonzaga de Figueiredo, Letícia Aparecida Cunha, Gabriella Maria Fernandes Oliveira, Laser Antônio Machado de Miranda, Marina Barcelos de Silva, Gisele Rodrigues da Moura, Sandra Aparecida Lima de |
author_role |
author |
author2 |
Figueiredo, Letícia Aparecida Cunha, Gabriella Maria Fernandes Oliveira, Laser Antônio Machado de Miranda, Marina Barcelos de Silva, Gisele Rodrigues da Moura, Sandra Aparecida Lima de |
author2_role |
author author author author author author |
dc.contributor.author.fl_str_mv |
Oliveira, Leandro Gonzaga de Figueiredo, Letícia Aparecida Cunha, Gabriella Maria Fernandes Oliveira, Laser Antônio Machado de Miranda, Marina Barcelos de Silva, Gisele Rodrigues da Moura, Sandra Aparecida Lima de |
dc.subject.por.fl_str_mv |
Biodegradable polymers Biomaterials Controlled release/delivery Targeted drug delivery Polymeric drug delivery systems |
topic |
Biodegradable polymers Biomaterials Controlled release/delivery Targeted drug delivery Polymeric drug delivery systems |
description |
In this study, the methotrexate (MTX) was incorporated into the poly(-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-_ and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile. C _ 2015Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 2016-07-25T16:21:12Z 2016-07-25T16:21:12Z |
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.uri.fl_str_mv |
OLIVEIRA, L. G. de et al. Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. Journal of Pharmaceutical Sciences, v. 104, p. 3731-3742, 2015. Disponível em: <http://www.sciencedirect.com/science/article/pii/S0022354916301599>. Acesso em: 16 jun. 2016. 1520-6017 http://www.repositorio.ufop.br/handle/123456789/6627 https://doi.org/10.1002/jps.24569 |
identifier_str_mv |
OLIVEIRA, L. G. de et al. Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity. Journal of Pharmaceutical Sciences, v. 104, p. 3731-3742, 2015. Disponível em: <http://www.sciencedirect.com/science/article/pii/S0022354916301599>. Acesso em: 16 jun. 2016. 1520-6017 |
url |
http://www.repositorio.ufop.br/handle/123456789/6627 https://doi.org/10.1002/jps.24569 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFOP instname:Universidade Federal de Ouro Preto (UFOP) instacron:UFOP |
instname_str |
Universidade Federal de Ouro Preto (UFOP) |
instacron_str |
UFOP |
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UFOP |
reponame_str |
Repositório Institucional da UFOP |
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Repositório Institucional da UFOP |
repository.name.fl_str_mv |
Repositório Institucional da UFOP - Universidade Federal de Ouro Preto (UFOP) |
repository.mail.fl_str_mv |
repositorio@ufop.edu.br |
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1813002820313415680 |