Long-lasting comfort ocular surface drug delivery by in situ formation of an adhesive lubricative Janus nanocoating

Topical drug delivery on ocular surface always suffers from frequent administration and low bioavailability due to short drug residence. Despite advances of different adhesive ophthalmic drugs in extending release, cornea and eyelid nonselective adhesion inevitably causes ocular discomfort and even damage. Here, we describe in situ formation of an adhesive lubricative Janus nanocoating (ALJN) to enable long-lasting comfort drug delivery. By iron complexation, an asymmetric ALJN is formed on ocular surface via facile sequential instillation. The adhesive polyphenol inner layer binding with ocular surface enables drug loading and sustained release, while the lubricative zwitterionic polymer outer layer prevents eyelid adhesion to ensure comfort. Following instillation, ALJN retains on ocular surface over 24 hours and reduces blinking frequency to normal level. Moreover, ALJN demonstrates remarkable therapeutic potential in mouse and rabbit models of corneal contusion and alkali burn. This work proposes a comfortable long-lasting topical delivery platform for treating various ocular diseases.