Echinacoside-Based Polycaprolactone Nanoparticles Boost Crosstalk Between Macrophages and Periodontal Ligaments During Periodontitis Therapy

Drug delivery by innovative nanoparticles into osteogenesis-associated cells has excellent potential for periodontitis therapy. However, a deep understanding of how the nanoparticles boost the bioactivity of delivered drugs is lacking. In this study, we evaluated the potential of echinacoside (ECH), a phenolic chemical, for periodontitis therapy by investigating how it regulates macrophages, human periodontal ligament cells (hPDLCs), and osteoclasts. Furthermore, we created ECH-based poly(-caprolactone) (PCL-ECH) nanoparticles to compare their efficacy to that of free ECH. In vitro data showed that the ECH significantly decreased the inflammatory responses in lipopolysaccharide-stimulated RAW264.7 macrophages but upregulated osteogenic factor BMP-2 expression. By modulating their crosstalk with macrophages and inhibiting osteoclast activities, ECH promoted inflammation-induced osteogenic differentiation of hPDLCs. Compared with the free ECH, the PCL-ECH nanoparticles enhanced the osteogenic differentiation of the hPDLCs by inducing ECH-modulated macrophage-hPDLC crosstalk. However, the bioactivities of the nanoparticles were comparable to the free ECH only in the macrophages or osteoclasts. The PCL-ECH nanoparticles induced more advanced alveolar bone remodeling (bone mineral density) than the free ECH In a ligature-induced periodontitis mouse model. This study provides deep insights into the nano-bio effect of ECH-based nanoparticles to investigate ways of promoting robust periodontitis therapy.