Azithromycin-loaded PLGA microspheres coated with silk fibroin ameliorate inflammation and promote periodontal tissue regeneration

作者：Zhaoguang Ouyang, Xiaoyu Chen, Zhengyang Wang, Yue Xu, Zhe Deng, Liangyu Xing, Li Zhang, Meilin Hu, Hanqi Li, Tengye Lian, Feng Gao, Chunyi Liu, Yangyang Zhou, Lu Sun, Ying Wang, Dayong Liu · 发表于：Regenerative Biomaterials · 年份：2024 · DOI：10.1093/rb/rbae146 · 被引用次数：10 · 研究领域：Periodontal Regeneration and Treatments、Oral microbiology and periodontitis research、Silk-based biomaterials and applications

Abstract Periodontitis, a widespread inflammatory disease, is the major cause of tooth loss in adults. While mechanical periodontal therapy benefits the periodontal disease treatment, adjunctive periodontal therapy is also necessary. Topically applied anti-inflammatory agents have gained considerable attention in periodontitis therapy. Although azithromycin (AZM) possesses excellent anti-inflammatory properties, its bioavailability is limited owing to poor water solubility and the absence of sustained release mechanisms. Herein, we synthesized biodegradable microspheres (AZM@PLGA-SF) for sustained AZM release to locally ameliorate periodontal inflammation and facilitate periodontal tissue regeneration. AZM was encapsulated in poly (lactic-co-glycolic acid) (PLGA) microspheres (AZM@PLGA) using single emulsion-solvent evaporation, followed by surface coating with silk fibroin (SF) via electrostatic adsorption, reducing the initial burst release of AZM. In vivo, local treatment with AZM@PLGA-SF microspheres significantly reduced periodontal inflammation and restored periodontal tissue to healthy levels. Mechanically, the formulated microspheres regulated the periodontal inflammatory microenvironment by reducing the levels of pro-inflammatory cytokines (tumor necrosis factor -α, interleukin [IL]-6, interferon-γ, IL-2, and IL-17A) in gingival crevicular fluid and promoted the expression of anti-inflammatory cytokines (IL-4 and IL-10). AZM@PLGA-SF microspheres demonstrated excellen...