Laboratory of Inflammation, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Pharmaceutical Sciences Post-Graduation Program, College of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
Int J Nanomedicine. 2019 Jul 12;14:5215-5228. doi: 10.2147/IJN.S200666. eCollection 2019.
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.
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.
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.
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.
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引起了关注，但它的口服生物利用度差是一个限制。在这项研究中，我们采用药物传递纳米技术来提高口服白藜芦醇的稳定性、肺定位和疗效，以控制导致 ALI 的肺损伤。
通过界面沉积生物可降解聚合物制备负载 RSV 的脂质核纳米胶囊（RSV-LNCs），在 LPS 鼻内滴注前给予 A/J 小鼠口服。在 LPS 攻击后 24 小时评估炎症变化、氧化应激和肺组织弹性。
RSV-LNCs（5mg/kg）在激发前 1、4、6 或 12 小时给予，但在 24 小时前给予，可抑制 LPS 诱导的支气管肺泡液（BALF）中白细胞积聚，而未负载的纳米胶囊（ULNCs）或游离 RSV（5mg/kg）则无效。RSV-LNCs（2.5-10mg/kg）而不是 ULNCs 或 RSV 在 LPS 攻击前 4 小时给予时，可改善肺功能并同样防止 BALF 和肺组织中总白细胞和中性粒细胞的积聚。在肺组织中产生一系列促炎细胞因子（如 IL-6、KC、MIP-1α、MIP-2、MCP-1 和 RANTES）方面也观察到类似的结果。此外，只有 RSV-LNCs 抑制了 LPS 激发后 MDA 水平和 SOD 活性的增加，并同时阻断了 ERK 和 PI3K/Akt 通路。
白藜芦醇在生物可降解油核聚合物中的纳米制剂是提高 RSV 抗 ALI 活性的有效策略，表明这种植物多酚的改良释放制剂在与 ALI 和呼吸衰竭相关的临床情况下可能具有重要价值。
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