Sripunya Aorada, Chittasupho Chuda, Mangmool Supachoke, Angerhofer Alexander, Imaram Witcha
Department of Chemistry, Faculty of Science, Kasetsart University, Bangkok 10900, Thailand.
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Chiang Mai University, Mueang, Chiang Mai 50200, Thailand.
Bioconjug Chem. 2024 Dec 18;35(12):1959-1969. doi: 10.1021/acs.bioconjchem.4c00475. Epub 2024 Dec 6.
Poly(amidoamine) (PAMAM) dendrimers have gained significant attention in various research fields, particularly in medicinal compound delivery. Their versatility lies in their ability to conjugate with functional molecules on their surfaces and encapsulate small molecules, making them suitable for diverse applications. Gallic acid is a potent antioxidant compound that has garnered considerable interest in recent years. Our research aims to investigate if the gallic acid-encapsulated PAMAM dendrimer generations 4 (G4(OH)-Ga) and 5 (G5(OH)-Ga) could enhance radical scavenging, which could potentially slow down the progression of age-related macular degeneration (AMD). Encapsulation of gallic acid in PAMAM dendrimers is a feasible alternative to prevent its degradation and toxicity. investigation of antioxidant activity was carried out using the DPPH and ABTS radical scavenging assays, as well as the FRAP assay. The IC values for DPPH and ABTS assays were determined through nonlinear dose-response curves, correlating the inhibition percentage with the concentration (μg/mL) of the sample and the concentration (μM) of gallic acid within each sample. G4(OH)-Ga and G5(OH)-Ga possess significant antioxidant activities as determined by the DPPH, ABTS, and FRAP assays. Moreover, gallic acid-encapsulated PAMAM dendrimers inhibit HO-induced reactive oxygen species (ROS) production in the human retinal pigment epithelium ARPE-19 cells, thereby improving antioxidant characteristics and potentially retarding AMD progression caused by ROS. In an evaluation of cell viability of ARPE-19 cells using the MTT assay, G4(OH)-Ga was found to reduce cytotoxic effects on ARPE-19 cells.
聚（酰胺胺）（PAMAM）树枝状大分子在各个研究领域都受到了广泛关注，尤其是在药物化合物递送方面。它们的多功能性在于能够与表面的功能分子共轭并封装小分子，使其适用于多种应用。没食子酸是一种有效的抗氧化化合物，近年来引起了广泛关注。我们的研究旨在探讨封装有没食子酸的第4代（G4(OH)-Ga）和第5代（G5(OH)-Ga）PAMAM树枝状大分子是否能增强自由基清除能力，这可能会减缓年龄相关性黄斑变性（AMD）的进展。将没食子酸封装在PAMAM树枝状大分子中是防止其降解和毒性的一种可行替代方法。使用DPPH和ABTS自由基清除试验以及FRAP试验进行抗氧化活性研究。通过非线性剂量反应曲线确定DPPH和ABTS试验的IC值，将抑制百分比与样品浓度（μg/mL）以及每个样品中没食子酸的浓度（μM）相关联。通过DPPH、ABTS和FRAP试验确定，G4(OH)-Ga和G5(OH)-Ga具有显著的抗氧化活性。此外，封装有没食子酸的PAMAM树枝状大分子可抑制人视网膜色素上皮ARPE-19细胞中HO诱导的活性氧（ROS）产生，从而改善抗氧化特性并可能延缓由ROS引起的AMD进展。在使用MTT试验评估ARPE-19细胞的细胞活力时，发现G4(OH)-Ga可降低对ARPE-19细胞的细胞毒性作用。
