One-Year Ultralong Intravitreal Release of Tyrosine Kinase Inhibitor from Supramolecular Temperature-Responsive Hydrogel

Retinal neovascular diseases, a leading cause of blindness, can be treated with intravitreal tyrosine kinase inhibitors (TKIs). Injectable intravitreal depots capable of sustained TKI release for more than 6 months are highly desirable. While existing platforms utilize covalently cross-linked hydrogels for prolonged release, thermoreversible hydrogels with good injectability have been deemed unsuitable for long-duration drug delivery due to rapid erosion from weak physical cross-linking. Here, we report the first injectable supramolecular hydrogel capable of 1-year sustained TKI release, prepared by codissolving an amphiphilic thermogel with the TKI. This hydrogel achieved a 12-fold longer drug-release duration compared to commercial Pluronic-F127 thermogel, arising from strong polymer-drug interactions resulting in a distinct gel microstructure and enhanced persistence. The released TKI retained bioactivity after one year, successfully resolving choroidal neovascularization (CNV) lesions in murine models. Our findings highlight the potential of supramolecular hydrogels for ultralong drug delivery to the retina.