Postoperative atrial fibrillation (POAF) is a common surgical complication linked to atrial inflammation and oxidative stress. Here, we developed a strategy integrating chemical modification of therapeutics, poly(lactic-co-glycolic acid) (PLGA)-mediated sustained kinetics, and hydrogel-enabled spatial targeting to achieve continuous, local drug delivery to the atrial region. Andrographolide was modified with phenylboronic acid (PBAn) to change its solubility and enhance drug-loading capacity in PLGA microspheres, while enabling responsive drug release. We further constructed an injectable bioadhesive hydrogel via mixing of a copolymer and O-carboxymethyl chitosan, which adhered to cardiac tissue. In vitro, PBAn demonstrated ROS-responsive release, along with anti-inflammatory and antioxidant effects on RAW264.7 and HL-1 cells. In a rat pericarditis model, this localized system significantly reduced atrial inflammation and oxidative stress, promoted anti-inflammatory M2 macrophage polarization, enhanced electrical stability, and markedly decreased POAF susceptibility.
Jianling Mo (2025) studied this question.