Trimethylated chitosan-coated flexible liposomes with resveratrol for topical drug delivery to reduce blue-light-induced retinal damage

LED-related blue-light-induced damage can cause eye diseases. However, drug delivery in patients with ocular diseases is faced with various challenges. In this study, we developed flexible liposomes based on trimethylated chitosan (TMC-Lipo) to deliver resveratrol for the treatment of retinal diseases. Flexible liposomes can easily cross various biological barriers. Chitosan and its derivatives have adhesive properties and are widely used in mucoadhesive drug delivery systems. Therefore, we wrapped flexible liposomes with trimethylated chitosan via electrostatic adsorption. The charge of the flexible liposomes became positive after encapsulation in TMC, and they remained stable in artificial tears. We assessed the safety of TMC-Lipo in cellular and zebrafish experiments and found that it can be safely used. In addition, treatment with TMC-Lipo significantly reduced H₂O₂-induced damage to ARPE-19 cells, restored mitochondrial membrane potential, and protected the cells. TMC-Lipo more easily reached the posterior ocular segment of the mice than liposome nanoparticles and attenuated blue-light-induced retinal cytopathy. Our study demonstrates that effective eye drop formulations can be developed based on trimethylated chitosan, which provides a promising approach for the treatment of ocular diseases.