Gallic Acid-Encapsulated\nPAMAM Dendrimers as an Antioxidant\nDelivery System for Controlled Release and Reduced Cytotoxicity against\nARPE-19 Cells

Poly(amidoamine)\n(PAMAM) dendrimers have gained significant\nattention\nin various research fields, particularly in medicinal compound delivery.\nTheir versatility lies in their ability to conjugate with functional\nmolecules on their surfaces and encapsulate small molecules, making\nthem suitable for diverse applications. Gallic acid is a potent antioxidant\ncompound that has garnered considerable interest in recent years.\nOur research aims to investigate if the gallic acid-encapsulated PAMAM\ndendrimer generations 4 (G4(OH)-Ga) and 5 (G5(OH)-Ga) could enhance\nradical scavenging, which could potentially slow down the progression\nof age-related macular degeneration (AMD). Encapsulation of gallic\nacid in PAMAM dendrimers is a feasible alternative to prevent its\ndegradation and toxicity. <i>In vitro</i> investigation\nof antioxidant activity was carried out using the DPPH and ABTS radical\nscavenging assays, as well as the FRAP assay. The IC<sub>50</sub> values\nfor DPPH and ABTS assays were determined through nonlinear dose–response\ncurves, correlating the inhibition percentage with the concentration\n(μg/mL) of the sample and the concentration (μM) of gallic\nacid within each sample. G4(OH)-Ga and G5(OH)-Ga possess significant\nantioxidant activities as determined by the DPPH, ABTS, and FRAP assays.\nMoreover, gallic acid-encapsulated PAMAM dendrimers inhibit H<sub>2</sub>O<sub>2</sub>-induced reactive oxygen species (ROS) production\nin the human retinal pigment epithelium ARPE-19 cells, thereby improving\nantioxidant characteristics and potentially retarding AMD progression\ncaused by ROS. In an evaluation of cell viability of ARPE-19 cells\nusing the MTT assay, G4(OH)-Ga was found to reduce cytotoxic effects\non ARPE-19 cells.