Mitochondria-targeted spathulenol-loaded retinosomes for age-related macular degeneration

Abstract

Age-related macular degeneration (AMD) is a leading cause of vision loss, with mitochondrial dysfunction playing a key role in its progression. This study explores the use of spathulenol, a natural sesquiterpene with anti-in flammatory and antioxidant properties, encapsulated in retinosomes—in novative exosome-derived nanoparticles from retinoid cells—for targeted drug delivery to retinal mitochondria. Retinosomes, with their innate affinity for retinal tissue and ability to cross biological barriers, provide a promising platform for this purpose (1, 2). The spathulenol-loaded retinosomes were characterized by a mean size of 97.3 nm, a zeta potential of +34.2 mV for col loidal stability, and an impressive encapsulation efficiency of 95.4%, ensuring efficient drug loading. In vitro release studies showed sustained spathulenol release from the retinosomes using a diffusion platform. To assess in vivo efficacy, an AMD mouse model was administered a sin gle intravenous dose of 300 mg/kg spathulenol-loaded retinosomes. Drug concentrations in the vitreous humor and circular vein were measured at multiple intervals, providing valuable pharmacokinetic data on ocular dis tribution and bioavailability. Further, genetic analysis before and after treat ment aimed to reveal spathulenol’s influence on mitochondrial function and AMD progression, potentially uncovering its effects on mitochondrial gene expression and related pathways. This study offers a thorough evaluation of mitochondria-targeted, spathu lenol-loaded retinosomes, encompassing their physicochemical properties, release kinetics, and in vivo pharmacokinetics and genetic effects. The find ings support the potential of this exosome-based delivery system for AMD therapy by addressing mitochondrial dysfunction.