Engineered Polymeric Nanocarriers Achieve Superior Antifibrotic and Vascular Protective Effects in Systemic Disease Models

Fibrosis and vascular remodeling remain critical challenges in systemic diseases, where conventional pharmacological interventions often show limited efficacy. In this study, we developed a PLGA-PEG-based functional nanocarrier and systematically evaluated its physicochemical properties, in vitro release behavior, and in vivo therapeutic potential. The nanocarriers exhibited uniform spherical morphology with an average size below 150 nm, a negative zeta potential, and high encapsulation efficiency (>75%). Controlled release profiles under different pH conditions demonstrated environment-responsive drug release, confirming their stability and suitability for systemic delivery. In a CCl₄-induced murine fibrosis model, nanocarrier treatment achieved a 78.4% reduction in fibrosis and a 45.6% attenuation of aortic dilation, significantly outperforming free drug administration. Histological analysis revealed markedly reduced collagen deposition and preserved tissue architecture, while serum biochemical assays indicated lowered ALT, AST, and MDA levels alongside increased antioxidant enzyme activities (GSH-Px, SOD). These findings highlight the synergistic anti-inflammatory, antioxidative, and antifibrotic effects of the nanocarrier system. This study demonstrates that rationally engineered polymeric nanocarriers can integrate long-circulation, targeted accumulation, and sustained release to achieve superior therapeutic outcomes in systemic fibrosis and vascular disease. Although further studies on long-term safety and clinical translation are required, the present findings provide a robust experimental basis and translational strategy for advancing nanomedicine toward clinical applications in systemic disease management.