Formulation and evaluation of probucol-LCA nanoparticles for supressing oxidative stress-related retinal degeneration

Retinal degenerative diseases are a major cause of vision loss worldwide, with oxidative stress being a key pathological driver. This study aimed to develop and evaluate probucol-lithocholic acid (LCA) nanoparticles for targeted retinal protection. Nanoparticles were formulated via spray drying of a mixture containing probucol, low-viscosity sodium alginate, polyethylene glycol, and LCA, followed by detailed physicochemical characterization. In vitro studies using human retinal pigment epithelial (ARPE-19) cells exposed to oxidative (H₂O₂) and hyperglycaemic stress demonstrated that the probucol-LCA nanoparticles significantly improved cell viability, reduced reactive oxygen species (ROS), restored glutathione (GSH) levels, and enhanced mitochondrial bioenergetics compared with non-functionalized formulations. In vivo, a single intravitreal injection of the nanoparticles in wild-type and retinal degeneration 1 (rd1) mice confirmed their biocompatibility and safety, showing no adverse effects on retinal structure or function. These findings establish the probucol-LCA nanoparticle system as a safe and effective antioxidant platform for intravitreal delivery. Its demonstrated in vitro efficacy and favourable safety profile highlight its potential for translation into therapeutic interventions for oxidative stress related retinal diseases.