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

Anterior segment diseases, including glaucoma and uveitis, affect millions of patients worldwide. Nanocarriers hold transformative potential for treating these conditions, yet corneal epithelium impermeability necessitates intraocular injection. Given the discomfort and infection risk, an injectable hydrogel-based depot offers a promising strategy for sustained delivery. 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, a composite hydrogel (C-gel) is presented that enables localized in situ gelation and sustained nanocarrier release within the anterior chamber. This is achieved by embedding poly(ethylene glycol)-b-poly(propylene sulfide) (PEG-b-PPS) filomicelles (FMs) within a crosslinked multi-arm PEG hydrogel. The FM structure facilitated the spatial confinement of DBCO- and azide-PEG crosslinking reactions, promoting efficient gel formation-the first use of FM morphology for enhanced localized gelation. As a result, 90% of the injected polymer is retained within the crosslinked matrix. Embedded FMs undergo oxidation-induced cylinder-to-sphere transitions, facilitating gradual release of micellar nanocarriers. The mechanical properties and release kinetics of C-gels can be specified by adjusting the formulation parameters. Sustained release of dye-loaded nanocarriers, used as a fluorescent model cargo, persisted for over a month under anterior chamber-mimicking conditions, underscoring the C-gel's potential as a long-acting depot for ocular drug delivery.