Intelligent Responsive PLGA-ES100 Composite Nanoparticles Loaded with Resolvin E1 for Inflammation Regulation Behavior

A persistent challenge in the use of biodegradable implants is the lack of precise spatiotemporal control over immune modulation at the implant site. This is particularly critical for materials, such as magnesium alloys, which generate a locally alkaline environment upon degradation. Here, we report a pH-responsive nanoparticle system composed of poly(lactide-<i>co</i>-glycolide) and Eudragit S100 (PLGA-ES100 NPs), engineered to degrade under alkaline conditions and enable on-demand release of the pro-resolving mediator Resolvin E1 (RvE1). The nanoparticles promote macrophage migration and polarization toward an anti-inflammatory M2 phenotype only under alkaline conditions, with TNF-α and IL-1β expression markedly suppressed following RvE1 release. When implanted subcutaneously with AZ31 magnesium alloys in rats, RvE1-loaded nanoparticles resulted in the thinnest fibrotic capsule (52.15 μm) and highest CD163 expression, confirming effective in vivo immunomodulation. In contrast, barrier coatings that restricted RvE1 release abrogated this response. This study establishes a strategy for leveraging implant-driven pH changes to trigger localized, inflammation-resolving drug release. The PLGA-ES100-RvE1 system offers a modular platform for controlling immune responses at bioresorbable implant interfaces.