School of Preclinical Medicine, Chengdu University, Chengdu 610106, China.
College of Electronics and Information Engineering, Sichuan University, Chengdu 610065, China.
ACS Appl Mater Interfaces. 2024 Sep 4;16(35):46090-46101. doi: 10.1021/acsami.4c09901. Epub 2024 Aug 22.
Epigallocatechin gallate (EGCG)-based nanosystems have garnered significant attention for their ability to alleviate inflammation due to their excellent anti-inflammatory properties and enhanced drug delivery capabilities. However, the degradation of EGCG in strongly acidic environments poses a challenge for potential administration, particularly in oral formulations, where gastric resistance is essential. In this study, we develop a "disintegration and reorganization" strategy to create acid-resistant antioxidant nanoparticles (EGA NPs) based on EGCG and 5-aminosalicylic acid (5-ASA) for mitigating inflammation in colitis and acute kidney injury. At acidic pH, the ester bond in EGCG breaks down, producing two building blocks. These, together with 5-ASA and formaldehyde, form oligomers through a combination of phenol-aldehyde condensation and the Mannich reaction. The resulting oligomers self-assemble into EGA NPs, which exhibit significant stability under both acidic and neutral pH conditions. This stability makes them suitable for oral administration, allowing them to withstand harsh gastric conditions, as well as for intravenous injection. Importantly, these oligomers retain the antioxidant and anti-inflammatory properties of EGCG, effectively scavenging reactive oxygen species and reducing intracellular oxidative stress. Additionally, EGA shows potential as a drug carrier, efficiently loading the anti-inflammatory agent curcumin (Cur) to form Cur@EGA NPs. In vivo studies demonstrate the efficacy of Cur@EGA and EGA in alleviating acute colitis and kidney injury following oral and intravenous administration, respectively. These nanoparticulate formulations exhibit superior inflammation reduction compared to free Cur in vivo. Overall, our findings introduce a novel acid-resistant nanoplatform based on EGCG for the treatment of acute inflammation.
没食子酸表没食子儿茶素酯（EGCG）基纳米系统因其出色的抗炎特性和增强的药物递送能力而备受关注，能够缓解炎症。然而，EGCG 在强酸环境中的降解对潜在的给药构成了挑战，特别是在口服制剂中，胃的抵抗力至关重要。在这项研究中，我们开发了一种“崩解和重组”策略，基于 EGCG 和 5-氨基水杨酸（5-ASA）创建了耐酸抗氧化纳米颗粒（EGA NPs），以减轻结肠炎和急性肾损伤中的炎症。在酸性 pH 下，EGCG 中的酯键断裂，产生两个构建块。这些构建块与 5-ASA 和甲醛一起通过酚醛缩合和曼尼希反应形成低聚物。所得低聚物通过自组装形成 EGA NPs，在酸性和中性 pH 条件下均表现出显著的稳定性。这种稳定性使其适合口服给药，使其能够耐受恶劣的胃环境，也适合静脉注射。重要的是，这些低聚物保留了 EGCG 的抗氧化和抗炎特性，有效地清除活性氧并减轻细胞内氧化应激。此外，EGA 显示出作为药物载体的潜力，能够有效负载抗炎剂姜黄素（Cur）形成 Cur@EGA NPs。体内研究表明，Cur@EGA 和 EGA 分别通过口服和静脉注射在缓解急性结肠炎和肾损伤方面具有疗效。这些纳米颗粒制剂在体内比游离 Cur 具有更好的抗炎效果。总体而言，我们的研究结果为急性炎症的治疗引入了一种基于 EGCG 的新型耐酸纳米平台。
