Anti-Oxidative Tannic Acid-Based Nanogels Formed via Dynamic Benzoxaborolate Cross-Linking at Physiological pH

Oxidative stress is identified as an important factor causing various ophthalmic diseases. Anti-oxidative nano-systems have been progressively developed as an emerging therapeutic approach. Herein, tannic acid (TA)-based nanogels (PBTA) with antioxidant activity were prepared via a one-step mixing process of TA and 4-arm polyethylene glycol modified with benzoxaborole (4aPB) at physiological pH (7.4) through dynamic benzoxaborolate cross-linking. The hydrodynamic size could be easily adjusted by varying the 4aPB: TA weight ratio. The optimized nanogels formed at the ratio of 5: 1 displayed a suitable hydrodynamic diameter of ∼ 140 nm with a narrow polydispersity index (PDI) of ∼ 0.1. The excellent free radical scavenging ability of PBTA nanogels was confirmed by both ABTS and DPPH assays, revealing the dynamic complexation of TA does not compromise its antioxidant property. Moreover, the nanogel formulation significantly augmented the storage stability and cytocompatibility of free TA. In addition, compared to free TA, PBTA nanogels demonstrated a comparable intracellular ROS-scavenging efficiency, while concurrently exhibiting a superior cytoprotective effect on ARPE-19 cells under oxidative injury. These results suggest that PBTA nanogels might be a promising natural polyphenol-based nanoantioxidant in combating oxidative stress-related ophthalmic disorders.