Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity.

Detalhes bibliográficos
Autor(a) principal: Oliveira, Leandro Gonzaga de
Data de Publicação: 2015
Outros Autores: 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
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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spelling 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
institution UFOP
reponame_str Repositório Institucional da UFOP
collection 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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