Ophthalmic Tethered Gold Yarnball-Mediated Retained Drug Delivery for Eye Fundus Disease Treatment.

Eye fundus diseases, such as retinal degenerative diseases, which lead to blindness in ≈12% of individuals aged >65 years, cause permanent damage to retinal cells. The antioxidant quercetin (QC) is promising for the effective treatment of eye fundus diseases; however, its poor solubility and low retention rate often limit its clinical application. Herein, an in situ ophthalmic tethered gold yarnball (GY) that doubles as an ocular retention agent and QC reservoir to overcome low fundus drug retention is developed. After intravitreal injection, QC@GYs enhance retinal cell leakage and internal limiting membrane permeability, facilitating the partial penetration of QC@GYs into the intraretinal tissue. The combination of retina-tethered QC@GY and first-level sustained release reduces macular degeneration in vivo by effectively regulating oxidative stress. Furthermore, the sustained release of QC preserves the viability of retinal pigment epithelium cells, reduces apoptosis, and suppresses drusen formation. This preservation of retinal morphology and function maximizes the therapeutic impact while minimizing the need for frequent intraocular administration. Overall, the ophthalmic tethered GY platform is a versatile tool for retinal drug delivery for the treatment of eye fundus diseases.