Two birds with one stone: natural polyphenols boosted periodontitis treatment of chlorhexidine via reducing toxicity and regulating microenvironments.

Chlorhexidine (CHX) is considered the gold standard for controlling periodontal plaque and has been extensively used as a topical agent in treating periodontitis. Nevertheless, the practical clinical application of CHX is still constrained by the inherent limitations of its properties, including toxicity, inadequate biofilm scavenging capacity, and single biological effect. In this study, polyphenolic epigallocatechin gallate (EGCG) has been employed to integrate with CHX to form an EGCG-CHX nanoplatform via a facile one-pot method. Due to the dynamic bonding between EGCG and CHX, the EGCG-CHX nanoparticles (NPs) show reduced toxicity and excellent response release behavior. Moreover, a series of in vitro and in vivo studies demonstrated that the EGCG-CHX NPs significantly enhanced the antibiofilm, antioxidative, anti-inflammatory, and autophagic flux activation effects of CHX, ultimately achieving an improved therapeutic effect on periodontitis. This study successfully developed a strategy boosting the efficiency of CHX for periodontitis treatment.