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

Abstract

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.

Poloxamer 407/188 Binary Thermosensitive Gel as a Moxidectin Delivery System: In Vitro Release and In Vivo Evaluation

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Injectable thermosensitive hydrogel to modulate tolerogenic dendritic cells under hyperglycemic condition

“…Current treatments for periodontitis include non-surgical and surgical debridement, coupled with local or systemic delivery of antibiotics. 2 While these treatments remove the source of infection (dental plaque), they don't address the subsequent immune-inflammatory healing response. Cell transplantation has been applied to attenuate periodontitis in animal models.…”

An injectable thermosensitive hydrogel with a self-assembled peptide coupled with an antimicrobial peptide for enhanced wound healing

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