A ROS-Responsive Polymer-Micelle Delivery System Designed for the Treatment of Drug-Induced Myocarditis

Background/Objectives: Drug-induced myocarditis lacks targeted therapies. Current glucocorticoid and immunosuppressant treatments suffer from poor lesion accumulation and systemic toxicity. We aimed to develop a ROS-responsive self-assembled nanocarrier (GSP) for the controlled release of glycyrrhetinic acid (GA) to inflamed myocardial tissue.

Methods

GSP was synthesized by conjugating GA and PEG via a thioketal linker. Micelles were characterized by NMR, DLS, and TEM. ROS-triggered drug release, cytotoxicity, cellular uptake, anti-inflammatory (TNF-α) and ROS-scavenging effects were evaluated in DOX-activated H9C2 cells. In vivo, biodistribution, echocardiography, inflammatory cytokines, and histopathology were assessed in an isoproterenol-induced mouse myocarditis model.