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

被引:0
作者
Wu, Yiping [1 ]
Wang, Lixu [4 ]
Hu, Chengda [2 ,3 ]
Tian, Ruikang [4 ]
机构
[1] Shandong First Med Univ, Eye Hosp, Jinan, Shandong, Peoples R China
[2] Wenzhou Med Univ, Affiliated Hosp 2, Wenzhou, Zhejiang, Peoples R China
[3] Wenzhou Med Univ, Yuying ChildrenS Hosp, Wenzhou, Zhejiang, Peoples R China
[4] Wenzhou Med Univ, Eye Hosp, State Key Lab Ophthalmol Optometry & Vis Sci, Wenzhou 325000, Zhejiang, Peoples R China
关键词
Anti-inflammatory; Endotoxin-induced uveitis; Caffeic acid; Eye drops; Nanoparticle; DRUG-DELIVERY; COPOLYMER MICELLES; ORAL DELIVERY;
D O I
10.1038/s41598-025-94296-4
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:9
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