A dual functional polypeptide with antibacterial and anti-inflammatory properties for the treatment of periodontitis

Periodontitis has been reported as the sixth most prevalent disease in human beings. This destructive disease is closely related to systemic diseases. Existing local drug delivery systems for periodontitis suffer from poor antibacterial effect and drug resistance. Inspired by the pathogenesis of periodontitis, we implemented a strategy to construct a dual functional polypeptide LL37-C15, which exhibited remarkable antibacterial effect against P. gingivalis and A. actinomycetemcomitans. In addition, LL37-C15 inhibits the release of pro-inflammatory cytokines by controlling the inflammatory pathway and reversing macrophage M1. Furthermore, the anti-inflammatory effect of LL37-C15 was also verified in vivo in a periodontitis rat model through the morphometry and histological observations of alveolar bone, hematoxylin-eosin, and Trap staining in gingival tissue. The results of molecular dynamics simulations showed that LL37-C15 could selectively destroy the bacterial cell membrane and protect the animal cell membrane in a self-destructive manner. The results showed that the polypeptide LL37-C15, as a novel promising therapeutic agent, exhibited a great potential for the periodontitis management. What's more, this dual functional polypeptide provides a promising strategy for building a multifunctional therapeutic platform against the inflammation and other diseases.