Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways

Maria Talita Pacheco de Oliveira,1 Diego de Sá Coutinho,1 Éverton Tenório de Souza,1 Sílvia Stanisçuaski Guterres,2 Adriana Raffin Pohlmann,3 Patricia Machado Rodrigues Silva,1 Marco Aurélio Martins,1 Andressa Bernardi11Laboratory of...

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Autores principales:	de Oliveira MTP, de Sá Coutinho D, Tenório de Souza É, Stanisçuaski Guterres S, Pohlmann AR, Silva PMR, Martins MA, Bernardi A
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	biodistribution drug delivery anti-inflammatory effect nanostructured lipid carriers Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/fdb6cb9f96db45518b22934d5af9993b
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spelling	oai:doaj.org-article:fdb6cb9f96db45518b22934d5af9993b2021-12-02T03:06:28ZOrally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways1178-2013https://doaj.org/article/fdb6cb9f96db45518b22934d5af9993b2019-07-01T00:00:00Zhttps://www.dovepress.com/orally-delivered-resveratrol-loaded-lipid-core-nanocapsules-ameliorate-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Maria Talita Pacheco de Oliveira,1 Diego de Sá Coutinho,1 Éverton Tenório de Souza,1 Sílvia Stanisçuaski Guterres,2 Adriana Raffin Pohlmann,3 Patricia Machado Rodrigues Silva,1 Marco Aurélio Martins,1 Andressa Bernardi11Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Pharmaceutical Sciences Post-Graduation Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; 3Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, BrazilBackground: Resveratrol (RSV) has attracted interest as an alternative drug for the treatment of acute lung injury (ALI) and other pulmonary diseases, but its poor oral bioavailability is a limitation. In this study, we employed drug delivery nanotechnology to improve the stability, lung localization and efficacy of orally administered resveratrol to control lung damage leading to ALI.Methods and materials: RSV-loaded lipid-core nanocapsules (RSV-LNCs), prepared by interfacial deposition of biodegradable polymers, were given orally to A/J mice prior to lipopolysaccharide (LPS) intranasal instillation. Inflammatory changes, oxidative stress and lung tissue elastance were assessed 24 h after LPS challenge.Results: RSV-LNCs (5 mg/kg), given 1, 4, 6 or 12 h but not 24 h before provocation, inhibited LPS-induced leukocyte accumulation in the bronchoalveolar fluid (BALF), whereas unloaded nanocapsules (ULNCs) or free RSV (5 mg/kg) were ineffective. RSV-LNCs (2.5–10 mg/kg) but not ULNCs or RSV improved lung function and prevented total leukocyte and neutrophil accumulation equally in both BALF and lung tissue when given 4 h before LPS challenge. Similar findings were seen concerning the generation of a range of pro-inflammatory cytokines such as IL-6, KC, MIP-1α, MIP-2, MCP-1 and RANTES in lung tissue. In addition, only RSV-LNCs inhibited MDA levels and SOD activity in parallel with blockade of the ERK and PI3K/Akt pathways following LPS provocation.Conclusion: Nanoformulation of RSV in biodegradable oil-core polymers is an effective strategy to improve the anti-ALI activity of RSV, suggesting that the modified-release formulation of this plant polyphenol may be of great value in clinical conditions associated with ALI and respiratory failure.Keywords: biodistribution, drug delivery, anti-inflammatory effect, nanostructured lipid carriersde Oliveira MTPde Sá Coutinho DTenório de Souza ÉStanisçuaski Guterres SPohlmann ARSilva PMRMartins MABernardi ADove Medical Pressarticlebiodistributiondrug deliveryanti-inflammatory effectnanostructured lipid carriersMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5215-5228 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	biodistribution drug delivery anti-inflammatory effect nanostructured lipid carriers Medicine (General) R5-920
spellingShingle	biodistribution drug delivery anti-inflammatory effect nanostructured lipid carriers Medicine (General) R5-920 de Oliveira MTP de Sá Coutinho D Tenório de Souza É Stanisçuaski Guterres S Pohlmann AR Silva PMR Martins MA Bernardi A Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
description	Maria Talita Pacheco de Oliveira,1 Diego de Sá Coutinho,1 Éverton Tenório de Souza,1 Sílvia Stanisçuaski Guterres,2 Adriana Raffin Pohlmann,3 Patricia Machado Rodrigues Silva,1 Marco Aurélio Martins,1 Andressa Bernardi11Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Pharmaceutical Sciences Post-Graduation Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil; 3Department of Organic Chemistry, Institute of Chemistry, Federal University of Rio Grande do Sul, Porto Alegre, BrazilBackground: Resveratrol (RSV) has attracted interest as an alternative drug for the treatment of acute lung injury (ALI) and other pulmonary diseases, but its poor oral bioavailability is a limitation. In this study, we employed drug delivery nanotechnology to improve the stability, lung localization and efficacy of orally administered resveratrol to control lung damage leading to ALI.Methods and materials: RSV-loaded lipid-core nanocapsules (RSV-LNCs), prepared by interfacial deposition of biodegradable polymers, were given orally to A/J mice prior to lipopolysaccharide (LPS) intranasal instillation. Inflammatory changes, oxidative stress and lung tissue elastance were assessed 24 h after LPS challenge.Results: RSV-LNCs (5 mg/kg), given 1, 4, 6 or 12 h but not 24 h before provocation, inhibited LPS-induced leukocyte accumulation in the bronchoalveolar fluid (BALF), whereas unloaded nanocapsules (ULNCs) or free RSV (5 mg/kg) were ineffective. RSV-LNCs (2.5–10 mg/kg) but not ULNCs or RSV improved lung function and prevented total leukocyte and neutrophil accumulation equally in both BALF and lung tissue when given 4 h before LPS challenge. Similar findings were seen concerning the generation of a range of pro-inflammatory cytokines such as IL-6, KC, MIP-1α, MIP-2, MCP-1 and RANTES in lung tissue. In addition, only RSV-LNCs inhibited MDA levels and SOD activity in parallel with blockade of the ERK and PI3K/Akt pathways following LPS provocation.Conclusion: Nanoformulation of RSV in biodegradable oil-core polymers is an effective strategy to improve the anti-ALI activity of RSV, suggesting that the modified-release formulation of this plant polyphenol may be of great value in clinical conditions associated with ALI and respiratory failure.Keywords: biodistribution, drug delivery, anti-inflammatory effect, nanostructured lipid carriers
format	article
author	de Oliveira MTP de Sá Coutinho D Tenório de Souza É Stanisçuaski Guterres S Pohlmann AR Silva PMR Martins MA Bernardi A
author_facet	de Oliveira MTP de Sá Coutinho D Tenório de Souza É Stanisçuaski Guterres S Pohlmann AR Silva PMR Martins MA Bernardi A
author_sort	de Oliveira MTP
title	Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
title_short	Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
title_full	Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
title_fullStr	Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
title_full_unstemmed	Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
title_sort	orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate lps-induced acute lung injury via the erk and pi3k/akt pathways
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/fdb6cb9f96db45518b22934d5af9993b
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Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways

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