Eye‐Drop Nano‐Formulation of Catalase Self‐Assembled with Thiolated Chitosan for Effective Treatment of Dry Eye Disease

• DOI: 10.1002/adma.202415353
• Publication Date: 2025-03-24T08:06:48Z
• Authors: Ming Shao; Yu Chai; Yutong Jiang; Xinyi Wu; Wenjie Xie; Jiayi Lu; Xuehui Fu; Yao He; Xiaofeng Zhang; Han Zhang; Zhuang Liu

AbstractDry eye disease (DED), the most prevalent ophthalmological condition worldwide, can cause severe ocular discomfort and even visual impairment. Effective yet safe therapeutics for severe DED are still highly demanded. Herein, considering the important role of excessive reactive oxygen species (ROS) in triggering DED, an eye‐drop nano‐formulation of catalase (CAT) self‐assembled with cysteine‐modified chitosan (CS‐Cys) is designed for DED treatment. Upon eye‐drop administration of CS‐Cys/CAT nanoparticles, CS‐Cys can form disulfide bonds with abundant thiols in the mucin layer of the tear film, anchoring catalase to the corneal surface. Thus the excess ROS accumulated on the ocular surface can be effectively eliminated, resulting in a regulated tear microenvironment. In mouse and rabbit models, it is verified that CS‐Cys/CAT eye drops can offer excellent therapeutic effects, especially in promoting the recovery of damaged epithelium and increasing tear secretion. Remarkably, CS‐Cys/CAT eye drops showed notably better therapeutic performance than clinically used cyclosporin and dexamethasone, as well as several new DED drugs in clinical trials. Thus, the work presents a unique nanoparticulate eye‐drop‐based ocular delivery system to allow prolonged ocular retention of protein therapeutics, and such nanoformulation formulated by fully biocompatible/biodegradable components possesses significant translational potential for effective and safe DED treatment.