Curcumin- loaded Pickering Emulsions with Immunomodulatory Ability for Treatment of Periodontitis

Periodontitis (PD) as a chronic inflammatory disease instigated by periodontal pathogenic bacteria and mediated by the host immune response, resulting in the destruction of supporting periodontal tissue and tooth loss in adults. Constructing an injectable delivery system that allows for sustained drug release within periodontal pockets to continuously eliminate pathogenic bacteria, reduce periodontal inflammation, and promote periodontal tissue regeneration is an effective strategy for periodontitis treatment. Here, we explore the therapeutic potential and underlying mechanisms of curcumin-loaded Pickering emulsion (PE-CUR) in periodontitis treatment. The Pickering emulsion formulation offers an effective delivery system, enhancing curcumin's bioavailability and therapeutic efficacy. In vitro studies, we demonstrate that the PE-CUR exhibit excellent biocompatibility and anti-inflammatory property by elimination of reactive oxygen species (ROS). In addition, PE-CUR significantly eliminate key periodontal pathogens, including Porphyromonas gingivalis (P. gingivalis) and Staphylococcus aureus (S. aureus). In a rat model of periodontitis, PE-CUR significantly attenuates periodontal tissue inflammation and alveolar bone loss, indicating a protective effect against periodontal tissue destruction. Mechanistically, PE-CUR promotes the expression of anti-inflammatory factors and inhibits the release of pro-inflammatory factors by regulating macrophage polarization from M1 to M2 and modulating the MAPK and PI3K-AKT signaling pathway. Furthermore, PE-CUR decreases the formation of osteoclasts as well as stimulates the activation and differentiation of osteoblasts successively, thereby ameliorating the periodontal inflammation and promoting the alveolar bone regeneration. Overall, our findings elucidate the therapeutic mechanisms of PE-CUR in periodontitis, suggesting its potential as a promising treatment strategy warranting further clinical investigation. Overall design: To investigate the anti-inflammatory and osteoclast-inhibitory effects of PE-CUR on RAW264.7 cells, we plated RAW264.7 cells in 24-well plates and treated them with 100 ng/mL lipopolysaccharide (LPS) and 2 mg/mL PE-CUR for 24 hours.

牙周炎（Periodontitis, PD）是一类由牙周致病菌诱发、经宿主免疫反应介导的慢性炎症性疾病，可导致成人牙周支持组织破坏与牙齿丧失。构建可在牙周袋内实现持续释药的可注射给药系统，以持续清除致病菌、减轻牙周炎症并促进牙周组织再生，是牙周炎治疗的有效策略。本研究探究了负载姜黄素的皮克林乳液（curcumin-loaded Pickering emulsion, PE-CUR）在牙周炎治疗中的治疗潜力与潜在作用机制。皮克林乳液制剂可作为高效递送系统，提升姜黄素的生物利用度与治疗效果。体外实验证实，PE-CUR可通过清除活性氧（reactive oxygen species, ROS）展现优异的生物相容性与抗炎特性。此外，PE-CUR可显著清除关键牙周致病菌，包括牙龈卟啉单胞菌（Porphyromonas gingivalis, P. gingivalis）与金黄色葡萄球菌（Staphylococcus aureus, S. aureus）。在大鼠牙周炎模型中，PE-CUR可显著减轻牙周组织炎症与牙槽骨吸收，展现出抵御牙周组织破坏的保护作用。机制层面，PE-CUR通过调控巨噬细胞由M1型极化为M2型，并调节丝裂原活化蛋白激酶（MAPK）与磷脂酰肌醇3-激酶-蛋白激酶B（PI3K-AKT）信号通路，促进抗炎因子表达并抑制促炎因子释放。此外，PE-CUR可减少破骨细胞形成，同时依次促进成骨细胞的激活与分化，进而改善牙周炎症并促进牙槽骨再生。综上，本研究阐明了PE-CUR在牙周炎治疗中的作用机制，提示其作为极具前景的治疗策略值得开展进一步临床研究。整体实验设计：为探究PE-CUR对RAW264.7细胞的抗炎与破骨细胞抑制作用，我们将RAW264.7细胞接种于24孔板，采用100 ng/mL脂多糖（lipopolysaccharide, LPS）与2 mg/mL PE-CUR分别处理细胞24小时。