The role of aromatic ring number in phenolic compound-conjugated chitosan injectables for sustained therapeutic antiglaucoma efficacy

The development of long-lasting therapeutic drug delivery system is greatly desired for effective treatment of glaucoma, a chronic and multifactorial disease. Herein, the roles of aromatic ring number in phenolic compound-conjugated chitosan injectables are exploited for achieving an advanced drug carrier with potent anti-inflammatory and anti-oxidant properties. Low and high number of aromatic rings can induce deleterious impacts on the pharmaceutical applications of injectables, whereas the compound with a moderate ring number is proved as the most efficient agent for boosting drug delivery performances and endowing the chitosan injectables with therapeutic properties. Kaempferol–conjugated injectable formulation reveals a remarkable effectiveness for intracameral pilocarpine administration, which can alleviate progressive glaucoma via simultaneously exerting multiple pharmacological activities to suppress ocular hypertension, inflammation, and oxidative stress. These findings provide a significant advance in understanding structure-property relationship of the phenolic compound-conjugated chitosan injectables as long-lasting therapeutic drug delivery systems for medical management of glaucoma.