The effect of doxycycline-containing chitosan/carboxymethyl chitosan nanoparticles on NLRP3 inflammasome in periodontal disease.

• Dox:CS/CMCS-NPs had good physicochemical properties and cytocompatibility. • Dox:CS/CMCS-NPs inhibited the growth of Porphyromonas gingivalis. • Dox:CS/CMCS-NPs inhibited the activation of NLRP3 inflammasome in HGFs. • Dox:CS/CMCS-NPs reduced the expression of IL-1β by inhibiting the NLRP3 inflammasome. A polyelectrolyte complex nanoparticle comprising chitosan (CS) and carboxymethyl chitosan (CMCS) was prepared (CS/CMCS-NPs) by ionic gelation, which was then used as a doxycycline carrier (Dox:CS/CMCS-NPs). The obtained CS/CMCS-NPs and Dox:CS/CMCS-NPs were characterized for various parameters and bacteriostatic ability against Porphyromonas gingivalis. The regulation of related genes and proteins of NLRP3 inflammasome and IL-1β in human gingival fibroblasts (HGFs) was characterized by qRT-PCR, western blotting and ELISA. The results showed that Dox:CS/CMCS-NPs had an orderly morphology and an excellent cytocompatibility. P. gingivalis was strongly inhibited by Dox:CS/CMCS-NPs contrasted with control group. Dox:CS/CMCS-NPs effectively down-regulated both gene and protein levels of NLRP3 inflammasome and IL-1β in HGFs. This study provides a new method for rational application of Dox in the clinical treatment of periodontal disease and a new direction for explaining the mechanism of action of Dox:CS/CMCS-NPs and more drug-carrying nanoparticles. [ABSTRACT FROM AUTHOR]