The study aimed to develop and experimentally substantiate the effectiveness of the innovative bioadhesive gel "PerioGard-Bioactive" for the complex treatment of periodontitis. The drug is based on a thermosensitive polymer, poloxamer 407, which provides a transition to a gel state at a temperature of 32.5 ° C and prolonged action in a periodontal pocket. The formulation includes three complementary modules: an antibiotic film complex (liposomal chlorhexidine and DNase I), an anti-inflammatory module (curcumin nanoparticles and resolvin E1), and a regenerative complex (EMD mimetic, hyaluronic acid, and mesenchymal stem cell exosomes). Experimental studies have demonstrated pronounced antimicrobial activity of the gel against key periodontal pathogens. The effectiveness against Porphyromonas gingivalis biofilms reached 92%, due to the synergistic effect of liposomal chlorhexidine and DNase I. The anti-inflammatory module reduced the level of TNF-α by 77% and IL-6 by 80% in in vitro models of inflammation. In an experiment on animals with induced periodontitis, a single application of the gel resulted in the formation of 68.2% of new bone tissue after 4 weeks, which was 2 times more effective than standard therapy. Bone mineral density reached 0.95 g/cm3 with a decrease in bone destruction to 0.41 mm. The drug is characterized by excellent cytocompatibility with preservation of 95-98% of cell viability and stability during storage for 6 months. The complex effect on all links of the pathogenesis of periodontitis allows us to recommend the development for clinical use as a promising alternative to existing treatment methods.
