Sustained intravitreal delivery of carnosic acid by RADA16 peptide hydrogel protects the retina in acute ocular hypertension.

This study investigates the use of RADA16 hydrogels for delivering carnosic acid (CA) in glaucoma treatment. Rheological tests at 0.5% (w/v), 1% (w/v), and 2% (w/v) concentrations showed significant elasticity, with Young's moduli of 30.18 Pa, 16.22 Pa, and 26.66 Pa, respectively. The 1% (w/v) concentration had the lowest stiffness, ideal for intravitreal injection. SEM revealed the hydrogel's porous microstructure. The RADA16-CA system provided sustained CA release over 72 h, peaking at 6 h. In vitro, high CA concentrations (≥ 256 μg/mL) were cytotoxic, but RADA16 and RADA16-CA enhanced cell proliferation. RADA16-CA demonstrated superior efficacy and biocompatibility. In an acute ocular hypertension model, RADA16-CA improved retinal health in rats by reducing retinal nerve fiber layer thickness, ROS-positive cells, and pro-inflammatory cytokines, while boosting cell survival and antioxidant activity.These findings highlight the potential of the RADA16-CA sustained-release system as an optimized approach for glaucoma treatment.