Non-antibiotic lipid complex-in-thermogel strikes twice: multimodal photosensitive antibacterial meets...

Periodontitis is a chronic oral disease characterized by gingival inflammation and periodontium injury due to repeated pathogenic bacteria infection and overactive inflammatory response. Multidrug resistance and the quick loss of antibiotics in the oral cavity create challenges for treatment. Therefore, a novel non-antibiotic-dependent pharmaceutical strategy is crucial for clinical treatment of periodontitis. In this study, we developed a lipid complex-in-thermogel delivery system (IQ-ML@Gel) co-loading the photosensitizer of indocyanine green and the immunomodulator of quercetin. IQ-ML@Gel could stably adhere in the periodontal pocket through liquid-solid transformation in situ. In vitro studies confirmed the efficient elimination of Porphyromonas gingivalis and Fusobacterium nucleatum by multimodal photothermal/photodynamic effects. Notably, IQ-ML displayed rapid macrophage uptake and an immunomodulatory effect through M1-M2 phenotypic polarization. In in vivo periodontitis treatment, IQ-ML@Gel effectively reverses the inflammatory microenvironment to promote periodontal tissue repair, including stimulating the regeneration of gingival collagen and alveolar bone. Overall, IQ-ML@Gel provides a promising non-antibiotic lipid complex-in-thermogel platform for periodontitis treatment.