Augmenting Therapeutic Potential of Polyphenols by Hydrogen-Bonding Complexation for the Treatment of Acute Lung Inflammation
Augmenting Therapeutic Potential of Polyphenols by Hydrogen-Bonding Complexation for the Treatment of Acute Lung Inflammation
复制标题
通过氢键络合增强多酚治疗急性肺部炎症的治疗潜力
DOI：
10.1021/acsabm.0c00616
复制
发表时间：
2020
影响因子：
4.7
通讯作者：
Yongming Chen
中科院分区：
文献类型：
--
作者：
Zhicheng Le;Zhijia Liu;Lilong Sun;Lixin Liu;Yongming Chen
炎症失调被认为是炎症相关疾病的重要病理过程，高水平的活性氧（ROS）产生引起氧化应激会加重炎症相关疾病。目前，多酚类化合物因其广泛的生物活性，如抗氧化和抗炎作用而受到广泛关注，但其稳定性差、血浆半衰期短、生物利用度低等缺点削弱了其治疗潜力。鉴于多酚具有广泛的结构特征和各种物理化学性质，绿色、大规模生产通用纳米载体以有效地包裹这些活性药物成分仍然是一个真正的挑战。在本研究中，我们采用闪速纳米络合（FNC）平台制备了由多酚和氢键激活的-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）组成的纳米配合物。我们证实了多酚的分子结构对其与TPGS的络合有很大的影响，当多酚的酚羟基数大于8时，形成稳定的纳米配合物。FNC装置生产的这些氢键纳米复合物具有均匀的尺寸、良好的胶体稳定性和高批间重复性，从而提高了作为抗氧化和抗炎应用的有效纳米治疗药物的可药性。体内实验表明，经鼻给药后，最佳纳米复合物（EGCG-NC）可用于改善小鼠急性肺损伤模型。这些结果证明，多酚与TPGS通过氢键络合形成纳米复合物，可以增强其在治疗急性肺部炎症时调节过度活跃炎症的治疗潜力。
Dysregulated inflammation is considered as an essential pathological process in inflammation-associated diseases, which would be aggravated by high levels of reactive oxygen species (ROS) generation inducing oxidative stress. Currently, extensive attention has been paid to polyphenolic compounds owing to their broad spectrum biological activities, such as antioxidant and anti-inflammatory effects, while their therapeutic potential has been compromised by the poor stability, short plasma half-life, and low bioavailability. Given that polyphenols have a wide range of structural characteristics and various physicochemical properties, there remains a real challenge toward green, mass production of universal nanocarriers for effective entrapment of these active pharmaceutical ingredients. In this study, we adopted a flash nanocomplexation (FNC) platform to prepare nanocomplexes comprising polyphenols andd-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) enabled by hydrogen bonding. We confirmed that the molecular structure of polyphenols has a great influence on their complexation with TPGS, and stable nanocomplexes were formed when the number of phenolic hydroxyl groups of polyphenols was above the value of 8. These hydrogen-bonded nanocomplexes produced by an FNC apparatus exhibited well-controlled quality with uniform size, good colloidal stability, and high batch-to-batch repeatability, thus improving the druggability as potent nanotherapeutics for antioxidant and anti-inflammatory applications.In vivoexperiments indicated that the optimal nanocomplex (EGCG-NC) can be applied to ameliorate acute lung injury in a mice model after nasal administration. These results proved that polyphenols formulated with TPGS for nanocomplex formation through hydrogen-bonding complexation could augment their therapeutic potential for modulating hyperactive inflammation in the treatment of acute lung inflammation.