High-efficiency antioxidant ROS-responsive thermosensitive hydrogel encapsulated Fenofibrate for the treatment of corneal neovascularization

Abstract

Corneal neovascularization (CNV) has become one of the common blinding ocular diseases recognized worldwide, affecting millions of people every year. Numerous studies have shown that oxidative stress and inflammation are important factors for the occurrence and development of CNV. In the present study, we established an antioxidant and reactive oxygen species (ROS) responsive thermosensitive hydrogel for long-acting drug delivery, combining with the loaded anti-angiogenic drug to the therapy for CNV. Se-PEG-PPG (SePEP) could in-situ gelling on the ocular surface temperature and cover the ocular surface. The hydrophobic interaction between the selenium ether segment and ocular mucin will further increase its adhesion on the ocular surface, which is conducive to drug Fenofibrate (Feno) retention and sustained release on the ocular surface. SePEP also played a role in reducing intracellular oxidative stress and oxidative responsive sustained release drug due to its selenium ether groups that scavenge ROS. Finally, the combined anti-oxidation, anti-inflammation, and anti-angiogenesis therapeutic effect of Feno@Se-PEG-PPG (SePEP-Feno) eye drops were demonstrated in a corneal neovascularization animal model. In conclusion, the multifunctional delivery system provided a promising method for the treatment of CNV and various ROS-related ocular diseases.