Porous aromatic frameworks-based sequential therapeutic strategy for the treatment of periodontitis

Abstract

Periodontitis is a prevalent oral disease, which affect up to 50% of the global population across a wide age spectrum. Due to the vicious cycle between "bacterial infection" and "host immunity", it is difficult to achieve efficient treatment with a single treatment strategy, so the sequential treatment strategy is urgently needed. Based on the pathological characteristics of periodontitis, the ideal treatment strategy should first rapidly kill the pathogenic bacteria, then eliminate ROS produced by both bacterial infection and host immunity, and finally anti-inflammatory treatment will be applied to the inflammatory caused by host immunity. However, sequential release often needs to release several drugs sequentially through a long period of time, so it is necessary to rely on drug carriers, which must have a large drug loading capacity and maintain longterm stability. Compared to other drug carriers, the properties of porous aromatic frameworks (PAFs) precisely meet the requirements and PAF-82 was employed. By sequentially loading diclofenac sodium (DS), coating with polydopamine (PDA) and adsorbing metronidazole (MTZ), PAF-DS@PDA-MTZ was constructed. The experimental results shown that PAF-DS@PDA-MTZ could quickly kill Porphyromonas gingivalis (P. g), eliminate ROS inhibition of pro-inflammatory factors, such as TNF-α and IL-6. Validation in a rat periodontitis model confirmed the system's efficacy in reducing alveolar bone resorption and enhancing periodontal healing efficiency. This strategy of coordinating antibacterial and anti-inflammatory effects through temporal regulation of drug release provides a novel therapeutic approach for bacteria-driven diseases.