Article
Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
Registro en:
OLIVEIRA, Maria Talita Pacheco de et al. Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways. International Journal of Nanomedicine, v. 14, p. 5215-5228, 2019.
1176-9114
10.2147/IJN.S200666
1178-2013
Autor
Oliveira, Maria Talita Pacheco de
Coutinho, Diego de Sá
Souza, Éverton Tenório de
Guterres, Sílvia Stanisçuaski
Pohlmann, Adriana Raffin
Silva, Patricia Machado Rodrigues
Martins, Marco Aurélio
Bernardi, Andressa
Resumen
Background: 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.