Contact lenses eluting atorvastatin-loaded ginger-exosomes: mechanistic modulation of oxidative and inflammatory...

Improved strategies for glaucoma management are urgently required due to poor bioavailability and limited retention of conventional ocular therapeutics. This study presents a novel approach: integrating atorvastatin (ATOR)-loaded, ginger-derived exosomes (G-EX) into contact lenses to achieve sustained release and enhanced ocular penetration. Exosomes were isolated from ginger using polymer precipitation, characterised (average size ≈ 50.3 ± 4.3 nm; zeta potential = -23.0 ± 1.2 mV), and efficiently loaded with ATOR (70 %). The ATOR@G-EX formulation was incorporated into contact lenses. Scanning electron and fluorescence microscopy confirmed uniform loading without altering lens structure. The lenses retained key properties, including high optical transmittance (96 %) and folding endurance (320 folds), supporting functional integrity and biocompatibility. In vitro assays showed controlled ATOR release (67 % in 2 h, gradual up to 48 h), following the Korsmeyer-Peppas model. Ex vivo, ATOR@G-EX lens markedly enhanced transcorneal permeation versus ATOR lens. In vitro cellular studies revealed higher fibroblast viability, faster migration, and 3-4-fold uptake improvement. HET-CAM confirmed minimal ocular irritation. In vivo, ATOR@G-EX lens produced the most pronounced and sustained IOP reduction in the steroid-induced glaucoma rabbit model, with a strong in vitro-in vivo correlation between permeation and efficacy. Treatment restored antioxidant enzyme (GPx 7.4 U/mL versus 3.2 U/mL in untreated positive group), normalised cytokines (TNF-α, IL-6), and modulated glaucoma markers (upregulated NRF2; downregulated IL-1β, TIMP, MYOC). Histology confirmed retinal neuroprotection and tissue recovery. In conclusion, this bioinspired ATOR@G-EX-loaded contact lenses show high safety, functionality, and compliance potential, providing a promising platform for patient-friendly ocular therapeutics and future clinical translation.