mPEG-PCL modified Caffeic acid eye drops for endotoxin-induced uveitis treatment.

The modulation of inflammatory mediators has emerged as a critical therapeutic strategy in uveitis management. Current nonsteroidal anti-inflammatory therapies face limitations due to systemic side effects. Caffeic acid (CA), a natural polyphenol with anti-inflammatory properties, holds therapeutic potential but suffers from poor solubility and ocular irritation. This study aimed to develop mPEG-PCL-modified CA-loaded nanoparticles (NanoCA) as a non-invasive eye drop formulation to enhance CA's solubility, bioavailability, and efficacy in treating endotoxin-induced uveitis (EIU). NanoCA was synthesized via the thin-film hydration method, characterized for size, zeta potential, drug loading, and release profile. Cytotoxicity was assessed in human corneal epithelial and RAW264.7 cells. Ocular tolerance was tested via slit-lamp and histopathological examinations. In vivo efficacy was evaluated in an EIU rat model using clinical scoring, histopathology, and immunofluorescence. NanoCA formed uniform nanospheres (42.40 ± 0.22 nm, -0.97 mV) with high encapsulation efficiency (99.17%). It exhibited sustained release over 12 h and reduced cytotoxicity compared to free CA. In EIU rats, NanoCA significantly suppressed inflammation, downregulated CD68 expression, and preserved aqueous barrier integrity. Histopathology confirmed minimal inflammatory infiltrates in NanoCA-treated eyes. The formulation demonstrated excellent ocular biocompatibility without corneal damage. NanoCA eye drops offer a safe, non-invasive therapeutic strategy for EIU, combining enhanced anti-inflammatory efficacy with high ocular tolerance. This nanoformulation presents a promising alternative to conventional CA delivery methods.