Green-synthesized N-acetylcarnosine–loaded gold nanoparticles as a novel ocular nanocarrier for antioxidant therapy and cataract prevention

Cataract represents one of the leading causes of blindness worldwide and is primarily attributed to protein glycation, oxidative stress, and aggregation of lens crystallins. Surgical lens extraction remains the standard treatment, which, despite its effectiveness, carries potential postoperative risks and economic burdens, thereby underscoring the need for alternative, non-surgical therapeutic approaches. This study aimed to develop a green-synthesized nanosystem based on gold nanoparticles (AuNPs) using Alchemilla vulgaris L. (Lady's mantle) extract, aiming to achieve efficient antioxidant delivery and sustained therapeutic retention within ocular tissues. Gold nanoparticles were synthesized via the reduction of chloroauric acid (HAuCl·3H₂O) using the plant extract under ultrasonic agitation and dispersion, yielding AuNPs formulations 1%, 4%, and 7% (w/v). The synthesized nanocomposites were characterized using a UV-Vis spectroscopy, FTIR, XRD, FE-SEM, AFM, and zeta potential analysis. Bio activity was performed using DPPH radical scavenging, MTT assays for cytotoxicity testing, in vitro drug-release studies, and ex-vivo lens transparency assessments, all supported by computational molecular docking and ADMET (absorption, distribution, metabolism, and excretion) analyses. The results demonstrated that NAC-loaded gold nanoparticles (NAC-AuNPs) exhibited enhanced antioxidant activity, achieving 72-89% DPPH inhibition, and a high encapsulation efficiency of 86.1%. The drug-release profile exhibited a higher release rate observed under mildly acidic conditions (pH 6). Ex-vivo experiments using human cataractous lenses revealed a dose-dependent improvement in lens optical clarity at NAC concentrations of 0.05, 0.1, and 0.3 mM, loaded onto 7% (w/v) AuNPs formulations. Molecular docking studies suggested potential hydrogen-bond interactions between NAC and key lens crystallin proteins, providing mechanistic insight into possible structural stabilization of lens crystallin proteins. The green-synthesized AuNP-NAC nanosystem may represents a promising and biocompatible nanocarrier strategy that warrants further in vivo validation.