Journal
ADVANCED SCIENCE
Volume 9, Issue 17, Pages -Publisher
WILEY
DOI: 10.1002/advs.202200435
Keywords
anti-inflammation; anti-oxidant stress; dry eye; micelles; vicious cycle
Categories
Funding
- National Key Research and Development Program of China [2020YFE0204400, 2018YFC1106104]
- National Natural Science Foundation of China [22005265, 82070939, 22105126, 81870641]
- Key Research and Development Project of Zhejiang Province [2020C03035]
- Zhejiang Provincial Natural Science Foundation of China [LBY21E030002]
- Natural Science Foundation of Shanghai [22ZR1433500]
- Zhejiang Provincial Ten Thousand Talents Program [2018R52001]
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The researchers have developed micelle-based eye drops for managing dry eye disease (DED), which includes inhibitors and scavengers to reduce inflammation and oxidative stress. This treatment effectively suppresses inflammation, repairs corneal defects, restores tear secretion, and alleviates DED symptoms.
Dry eye disease (DED) impacts approximate to 30% of the world's population and causes serious ocular discomfort and even visual impairment. Inflammation is one core cause of the DED vicious cycle, a multifactorial deterioration in DED process. However, there are also reactive oxygen species (ROS) regulating inflammation and other points in the cycle from the upstream, leading to treatment failure of current therapies merely targeting inflammation. Accordingly, the authors develop micelle-based eye drops (more specifically p38 mitogen-activated protein kinases (MAPK) inhibitor Losmapimod (Los)-loaded and ROS scavenger Tempo (Tem)-conjugated cationic polypeptide micelles, designated as MTem/Los) for safe and efficient DED management. Cationic MTem/Los improve ocular retention of conjugated water-soluble Tem and loaded water-insoluble Los via electrostatic interaction with negatively charged mucin on the cornea, enabling an increase in therapeutic efficiency and a decrease in dosing frequency. Mechanistically, MTem/Los effectively decrease ROS over-production, reduce the expression of proinflammatory cytokines and chemokines, restrain macrophage proinflammatory phenotypic transformation, and inhibit cell apoptosis. Therapeutically, the dual-functional MTem/Los suppress the inflammatory response, reverse corneal epithelial defect, save goblet cell dysfunction, and recover tear secretion, thus breaking the vicious cycle and alleviating the DED. Moreover, MTem/Los exhibit excellent biocompatibility and tolerability for potential application as a simple and rapid treatment of oxidative stress- and inflammation-induced disorders, including DED.
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