期刊
MOLECULAR PHARMACEUTICS
卷 18, 期 5, 页码 1992-2003出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.0c01196
关键词
targeted drug delivery; thermoresponsive hydrogel; poloxamer; pyrophosphate; simvastatin; periodontitis
资金
- National Institute of Allergy and Infectious Diseases of the National Institutes of Health, United States [R01 AI119090]
- College of Pharmacy, University of Nebraska Medical Center, United States [201707060010, 201907067014]
- China Scholarship Council
SIM is an effective anti-inflammatory and bone anabolic agent, but challenges including poor water solubility hinder its local delivery into periodontal pockets. Researchers developed a novel thermoresponsive hydrogel based on PF127 to dissolve SIM and mitigate periodontal bone loss.
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.
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