Thermoresponsive Hydrogel-Based Local Delivery of Simvastatin for the Treatment of Periodontitis.

Except for routine scaling and root planing, there are few effective nonsurgical therapeutic interventions for periodontitis and associated alveolar bone loss. Simvastatin (SIM), one of the 3-hydroxy-3-methylglutaryl-cosenzyme A reductase inhibitors, which is known for its capacity as a lipid-lowering medication, has been proven to be an effective anti-inflammatory and bone anabolic agent that has shown promising benefits in mitigating periodontal bone loss. The local delivery of SIM into the periodontal pocket, however, has been challenging due to SIM's poor water solubility and its lack of osteotropicity. To overcome these issues, we report a novel SIM formulation of a thermoresponsive, osteotropic, injectable hydrogel (PF127) based on pyrophosphorolated pluronic F127 (F127-PPi). After mixing F127-PPi with F127 at a 1:1 ratio, the resulting PF127 was used to dissolve free SIM to generate the SIM-loaded formulation. The thermoresponsive hydrogel's rheologic behavior, erosion and SIM release kinetics, osteotropic property, and biocompatibility were evaluated in vitro. The therapeutic efficacy of SIM-loaded PF127 hydrogel on periodontal bone preservation and inflammation resolution was validated in a ligature-induced periodontitis rat model. Given that SIM is already an approved medication for hyperlipidemia, the data presented here support the translational potential of the SIM-loaded PF127 hydrogel for better clinical management of periodontitis and associated pathologies.

ApAGP-fabricated silver nanoparticles induce amendment of murine macrophage polarization.

M2 polarization of macrophages is predominant in case of tumors and some other infectious diseases for disease progression. Repolarization of the M2 phenotype to the M1 state may be required to cure diseases. Hence, it is of great interest to find out a material that would repolarize the M2 phenotype to the M1 state. Herein, the arabinogalactan protein from Andrographis paniculata (ApAGP) was used to prepare a silver nanoparticle-ApAGP (SNP-ApAGP) bioconjugate, which was characterized via UV-vis spectroscopy, zeta potential analysis, FT-IR spectroscopy, and HR-TEM. Studies suggest that SNP-ApAGP (2.5 µg mL-1) up-regulates ROS generation, NO generation, and pro-inflammatory cytokine release (IL-12, IFN-γ, TNF-α, and IL-6). SNP-ApAGP also down-regulates the arginase-1 activity and anti-inflammatory cytokine release (IL-4 & IL-10) in M0, M1, and M2-polarized peritoneal macrophages in vitro. Therefore, SNP-ApAGP induces M1 polarization in M0 macrophages, enhances the pro-inflammatory activity of the M1 phenotype, and can also repolarize M2 macrophages into the M1 phenotype. Therefore, SNP-ApAGP could be used for treating various infectious diseases and cancers where repolarization of M2 macrophages may be required to cure the disease.