Dry Eye Disease (DED) is a multifactorial ocular disorder driven by inflammation, oxidative stress, and microbial imbalance. In pursuit of a sustainable therapeutic alternative, this study developed a novel ophthalmic hydrogel (HAZ@gel) incorporating polyphenol-rich hazelnut cuticle (HC) extracts obtained via Natural Deep Eutectic Solvents (NADES), embedded into a Carbopol-based matrix. A wide panel of NADES combinations was screened to optimize extraction efficiency, resulting in acid-based NADESs delivering the highest total phenolic content with favorable physicochemical properties. The HAZ@gel formulation demonstrated excellent biocompatibility and sustained polyphenol release, along with significant antioxidant and antiinflammatory activity in hyperosmotic-stressed human corneal epithelial cells, a validated in vitro DED model. The formulation also exerted antimicrobial effects against Bacillus subtilis and Escherichia coli, further supporting its multifunctional potential. This work exemplifies a circular economy strategy by valorizing agro-industrial waste through green extraction and eco-friendly formulation, proposing a biodegradable and efficacious ocular therapy aligned with sustainable pharmaceutical innovation.
Green-sourced polyphenols for ocular health: A sustainable NADES-based approach to dry eye disease treatment
Fabrizia Sepe;Viviana Chiappini;Loredana Marcolongo
;Sabrina Margarucci;Orsolina Petillo;Giuseppe Ruggiero;Diego Circolo;Anna Valentino
;Gianfranco Peluso;Anna Calarco
2026
Abstract
Dry Eye Disease (DED) is a multifactorial ocular disorder driven by inflammation, oxidative stress, and microbial imbalance. In pursuit of a sustainable therapeutic alternative, this study developed a novel ophthalmic hydrogel (HAZ@gel) incorporating polyphenol-rich hazelnut cuticle (HC) extracts obtained via Natural Deep Eutectic Solvents (NADES), embedded into a Carbopol-based matrix. A wide panel of NADES combinations was screened to optimize extraction efficiency, resulting in acid-based NADESs delivering the highest total phenolic content with favorable physicochemical properties. The HAZ@gel formulation demonstrated excellent biocompatibility and sustained polyphenol release, along with significant antioxidant and antiinflammatory activity in hyperosmotic-stressed human corneal epithelial cells, a validated in vitro DED model. The formulation also exerted antimicrobial effects against Bacillus subtilis and Escherichia coli, further supporting its multifunctional potential. This work exemplifies a circular economy strategy by valorizing agro-industrial waste through green extraction and eco-friendly formulation, proposing a biodegradable and efficacious ocular therapy aligned with sustainable pharmaceutical innovation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.


