Highly effective corneal permeability of reactive oxygen species-responsive nano-formulation encapsulated cyclosporine a for dry eye management

Dry eye disease (DED) has become a globally recognized public health problem with complex pathogenesis. Recent studies showed that oxidative stress damage and its induced inflammation are the main contributors to the occurrence and progression of dry eye. Here, a novel antioxidative and reactive oxygen species (ROS)-responsive micellar system is reported to improve the ocular surface delivery of highly hydrophobic immuno-suppressive cyclosporine A (CSA). This drug carrier is utilized together with the loaded anti-inflammatory drug to achieve a combinatorial treatment of DED. In detail, the selenium substituted random copolymer Se-PEG-PPG is the key to such design, which self-assembles into cornea-penetrating nanoscale micelles with a neutral shell and small size (<50 nm). The Se-PEG-PPG micelles also exerted synergetic therapeutic effects by decreasing intracellular oxidative stress and inhibiting cell apoptosis because of the ROS-scavenging selenium ether group. Finally, the combinatorial anti-oxidation, anti-inflammation, and therapeutic effects of CSA@Se-PEG-PPG eye drops were demonstrated in a murine dry eye model. Taken together, this multifunctional drug delivery system provides a promising approach for the treatment of DED and various ROS-related ocular diseases.

Automated summary

Dry eye disease (DED) is a globally recognized complex problem caused by oxidative stress damage and inflammation. A new micellar system with antioxidative and ROS-responsive properties is developed to enhance the delivery of hydrophobic cyclosporine A (CSA) for DED treatment. The micelles self-assemble from a selenium substituted random copolymer, which can penetrate the cornea due to its small size and neutral shell. The micelles not only deliver CSA but also reduce oxidative stress and inhibit cell apoptosis through ROS-scavenging selenium ether group. The efficacy of CSA@Se-PEG-PPG eye drops in treating DED is demonstrated in a mouse model, showing promising potential for the treatment of DED and other ROS-related ocular diseases.