Development of reactive oxygen species-sensitive polyethylene glycol-modified voriconazole-loaded nanomicelles for treating fungal keratitis.

In fungal keratitis (FK), excessive reactive oxygen species (ROS) accumulation at the inflammation site primarily promotes hyphal transformation in Candida albicans (CA). Therefore, ROS scavenging is beneficial for suppressing CA hyphal formation and FK-associated inflammation. This study aimed to synthesize an ROS-sensitive micellar material (SPS) and use it to encapsulate voriconazole, resulting in the formation of an ROS-responsive drug-loaded nanomicelle (SPSV). In addition, the microstructure, drug-loading capacity (90.90 % ± 0.39 %), encapsulation efficiency (5.71 % ± 0.02 %), ROS-triggered drug-release behavior, cytotoxicity, and in vitro and in vivo antifungal and anti-FK effects of the nanomicelles were systematically investigated. Results indicate that SPSV effectively released drugs in response to ROS, thereby scavenging ROS, inhibiting CA hyphal formation, and combating biofilm development. Moreover, SPSV effectively reduced FK-associated inflammation and exhibited favorable biocompatibility. This study provides a formulation and therapeutic strategy for combating CA and treating FK.