Therapeutic hydrogel sheets programmed with multistage drug delivery for effective treatment of corneal abrasion

Corneal abrasion (CA) is a leading cause of inflammation, scar formation, and even loss of vision in the eye if allowed to progress; however, current treatments remain constrained by complex and sequential conditions that impede access to most therapies for progressively abraded corneas. Herein, an advanced therapeutic hydrogel sheet (THS) constructed via electrostatic assembly of a functional hydrogel and a ternary drug-carrier system is reported. Specifically, the functional hydrogel comprises a poly(hydroxyethyl methacrylate), a positively charged chitosan, and zinc oxide nanoparticles. The ternary drug-carrier system is composed of dipalmitoylphosphatidylcholine liposome (DPPC) nanoparticles containing epigallocatechin gallate (EGCG) and hyaluronic acid nanoparticles with low and high crosslinking degrees, which separately carrying β-1,3-glucan and SB431542. Owing to the tailored degradability of the ternary system, the THS is able to provide multistage drug release, consequently allowing successive drug administration onto an ocular surface afflicted with CA for the suppression of inflammatory response in the early stage (by the fastest released EGCG) of corneal tissue repair, followed by promotion of wound healing in the middle stage (the moderately fast released β-1,3-glucan) and prevention of scar formation in the final stage (by the slowest released SB431542). In a rabbit model of CA, the THS has a significant treatment efficacy for repairing injured cornea tissues and demonstrates a percent recovery of greater than 90%, which represents a more than eight-fold improvement compared to conventional eye drops. The therapeutic hydrogel material demonstrated here can adapt to a variety of drug molecules, opening up a new avenue for the treatment of complex ocular diseases.