Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
Orally delivered resveratrol-loaded lipid-core nanocapsules ameliorate LPS-induced acute lung injury via the ERK and PI3K/Akt pathways
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DOI：
10.2147/ijn.s200666
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发表时间：
2019-01-01
影响因子：
8
通讯作者：
Bernardi, Andressa
中科院分区：
文献类型：
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作者：
Pacheco de Oliveira, Maria Talita;Coutinho, Diego de Sa;Bernardi, Andressa
背景：白藜芦醇(RSV)作为治疗急性肺损伤(ALI)和其他肺部疾病的替代药物已引起人们的兴趣，但其口服生物利用度较低。本研究利用纳米给药技术来改善口服白藜芦醇控制ALI所致肺损伤的稳定性、肺定位和疗效。方法和材料：A/J小鼠鼻腔滴注脂多糖(LPS)前，用生物可降解聚合物界面沉积法制备RSV脂核纳米胶囊(RSV-LNC)。结果：RSV-LNCs(5 mg/kg)在激发前1、4、6、12 h给药(而不是24 h)可抑制LPS诱导的小鼠肺泡灌洗液(BALF)中白细胞聚集，而未加载纳米胶囊(ULNCs)或游离RSV(5 mg/kg)对此无明显影响。RSV-LNCs(2.5~10 mg/kg)可明显改善肺功能，并能同样抑制BALF和肺组织中白细胞和中性粒细胞的聚集。在肺组织中产生的一系列促炎细胞因子，如IL-6、KC、MIP-1α、MIP-2、MCP-1和RANTES也有类似的发现。此外，只有RSV-LNC在阻断ERK和PI3K/Akt信号转导通路的同时抑制MDA水平和SOD活性。结论：在可生物降解的油芯聚合物中纳米制剂RSV是提高RSV抗ALI活性的有效策略，提示这种植物多酚的修饰释放制剂可能在与ALI和呼吸衰竭相关的临床条件下具有重要价值。
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-1 alpha, 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.