Anti-oxidative and mucin-compensating dual-functional nano eye drops for synergistic treatment of dry eye disease

Abstract

Oxidative stress plays a central role in dry eye disease (DED), which can destroy the mucin layer on the ocular surface. The currently available eye drops are palliative and short-lived. Thus, a therapy that can continuously scavenge the overexpressed reactive oxygen species (ROS) and promote mucin production in DED is quite necessary. Thus, we have developed a synergistic nanoparticle (NP) that can treat DED by scavenging ROS and promoting mucin production. Mesoporous polydopamine (mPDA) NPs were prepared by one-pot synthesis and loaded with melatonin (Mel) and tavilermide (Tav) (mPDA@Mel-Tav). The mPDA NPs loaded with 20% Mel and 2% Tav showed good cytocompatibility. Mel and Tav were continuously released from mPDA@Mel-Tav NPs, and the release of Mel was slower than that of Tav. The ROS level and apoptosis ratio were decreased in the presence of mPDA@Mel-Tav, indicating the central role of Mel in ROS scavenging and antioxidant effect. Meanwhile, Tav promoted the production of mucins on the ocular surface. The retention time of mPDA was longer than that of normal eye drops. The corneal fluorescence staining score of mice with DED in mPDA@Mel-Tav treatment group was lower than in other treated groups, indicating the good therapeutic effect of mPDA@Mel-Tav in DED. In summary, we synthesized the mPDA@Mel-Tav NP eye drop to achieve a sustained release of Mel and Tav, which could effectively treat DED by scavenging ROS and promoting mucin production. This dual-functional NP represents a promising treatment strategy for DED and other multi-cause diseases.