Sorafenib nanoparticles coated with Eudragit RL for ocular drug delivery: a potential treatment for diabetic retinopathy.

Diabetic retinopathy, a leading cause of vision impairment, is characterized by pathological retinal neovascularization driven by chronic hyperglycemia. Current treatments, including laser therapy and intravitreal injections, are invasive, limiting patient compliance. To address these challenges, we developed Eudragit RL (EUD)-coated hyaluronic acid (HA)-bovine serum albumin (BSA) nanoparticles (HB㊏EUD) loaded with sorafenib (SFB@(HB㊏EUD)) for targeted ocular drug delivery. The nanoparticles were prepared using an emulsification-evaporation thermal cross-linking method assisted by electrostatic interaction, yielding spherical particles of uniform size, with a particle size of 242.2 ± 1.9 nm (PDI = 0.19). The EUD coating significantly altered the nanoparticles' surface, transitioning the zeta potential from -40.6 ± 0.9 mV to -20.6 ± 0.5 mV. This change indicated a reduction in overall negative charge density and potential exposure of positively charged functional groups, facilitating electrostatic interactions with ocular mucin and prolonging corneal retention. Compared to unmodified nanoparticles, SFB@(HB㊏EUD) exhibited a 1.55-fold improvement in transcorneal transport and a 2.46-fold higher vitreous accumulation. In the chick chorioallantoic membrane assay, a 17.33% reduction in neovascularization was observed, further demonstrating the potent anti-angiogenic effects. In streptozotocin (STZ)-induced DR mice, treatment with SFB@(HB㊏EUD) via topical eye drops significantly reduced vascular leakage, preserved retinal structure, and suppressed vascular endothelial growth factor (VEGF) expression by 32.1%, outperforming non-functionalized nanoparticles. Fundus imaging and fluorescein angiography confirmed restored retinal perfusion and minimal vascular abnormalities. These findings highlight the potential of SFB@(HB㊏EUD) as a non-invasive, targeted therapy for DR, leveraging EUD's mucoadhesive properties and sorafenib's anti-angiogenic activity.