Filomicelle-Embedded Composite Hydrogels for Localized Gelation within the Anterior Chamber of the Eye

Nanocarriers hold transformative potential for treating anterior segment eye diseases, yet corneal epithelium impermeability necessitates intraocular injection. Given the discomfort and infection risk, an injectable hydrogel-based depot offers a promising strategy for sustained nanocarrier delivery in intraocular therapy. However, because the aqueous humor is a large, fluid-filled environment, achieving spatially confined gelation remains a key challenge as injected materials rapidly diffuse. Herein, we present a composite hydrogel (C-gel) that enables localized in situ gelation and sustained nanocarrier release within the anterior chamber. This is achieved using poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) filomicelles (FMs), whose filamentous structure confines crosslinking reactions spatially, promoting efficient gel formation. As a result, 90% of the injected polymer is retained within the crosslinked hydrogel matrix. Embedded FMs then undergo oxidation-induced cylinder-to-sphere transitions, facilitating gradual release of micellar nanocarriers. The rheological properties, gelation timing, and microstructure of the C-gel are adjustable, allowing precise control of nanocarrier release dynamics. In vivo evaluation in mice confirmed excellent biocompatibility without inducing intraocular pressure elevation, ocular toxicity, or immune cell infiltration. Sustained release of nanocarriers was observed for over a month under conditions mimicking that of the anterior chamber of the eye, underscoring the potential of C-gels for long-term drug delivery in anterior segment eye diseases therapy.