In situ bioactive nanocoating enables transocular delivery of permeable drug for dual-location intervention of ocular surface and fundus disorders.

The concurrency of ocular surface and fundus disorders is prevalent, posing a major threat to vision and quality of life. However, current therapies are difficult to simultaneously manage these coexisting symptoms. Here, we report a dual-location intervention strategy by in situ forming a permeable drug-carried bioactive nanocoating on ocular surface following instillation. The nanocoating is readily generated via dropping a mixture of polyphenol, metal ions, liposomes, and permeable drug. The coordination of metal ions with polyphenol and lipid enables nanocoating formation and its durable adhesion to ocular surface. The introduced bioactive polyphenol and liposomes separately provide anti-inflammatory activity and tear film-forming lipid to synergistically alleviate ocular surface disorder. In addition, the resulted network structure of the nanocoating offers continuous release of permeable drug, achieving intraocular delivery to mitigate the fundus symptom. Supported by the potency in synchronously intervening diabetic keratopathy and retinopathy in both streptozotocin-induced and Ins2-C96Y transgenic mouse models, this work opens a window for treating ocular diseases.