title: Effect of Simvastatin Prodrug on Experimental Periodontitis.
abstract: Local application of statins has shown potential in preventing and regenerating bone loss associated with experimental periodontitis. This study evaluates the effect of a novel simvastatin (SIM) prodrug (capable of delivering high doses to periodontitis inflammatory lesion and cells) on experimental periodontitis bone loss and inflammation.
  
  
  
  Forty mature female Sprague Dawley rats were subjected to ligature-induced experimental periodontitis between maxillary first and second molars (M1-M2). Equal groups were treated with three weekly doses of: 1) prodrug carrier alone (mPEG); 2) 0.5 mg SIM dose equivalent in carrier (SIM/SIM-mPEG); 3) 1.0 mg SIM/SIM-mPEG; 4) 1.5 mg SIM/SIM-mPEG; or 5) ligature alone. Contralateral molars served as unmanipulated controls. Four weeks after initiation of periodontitis, animals were euthanized, the M1-M2 interproximal was evaluated with microcomputed tomography and histology, and data were analyzed with one-way analysis of variance.
  
  
  
  Ligature alone caused a mean bone loss of 1.01 ± 0.06 mm from the cemento-enamel junction, whereas all doses of SIM/SIM-mPEG reduced bone loss, especially 1.5 mg SIM/SIM-mPEG (0.68 ± 0.05 mm, P <0.001), which was not statistically different from contralateral control (0.47 ± 0.06 mm). A dose of 1.5 mg SIM/SIM-mPEG also reduced percentage of neutrophils compared with carrier alone (2.0% ± 1.0% versus 5.7% ± 1.1%; P <0.05), and increased amount of uninflamed connective tissue in the M1-M2 interproximal area (65.2% ± 3.3% versus 46.3% ± 3.3%; P <0.001). The mPEG carrier alone did not have bone-sparing or anti-inflammatory properties.
  
  
  
  Multiple local 1.5-mg doses of a macromolecular SIM prodrug decreases amount of experimental periodontitis bone loss and inflammation in rats.
authors.affiliation: Department of Surgical Specialties, University of Nebraska Medical Center College of Dentistry, Lincoln, NE.
authors.forename: Aaron D
authors.initials: AD
authors.lastname: Bradley
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center College of Pharmacy, Omaha, NE.
authors.forename: Yijia
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center College of Pharmacy, Omaha, NE.
authors.forename: Zhenshan
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center College of Pharmacy, Omaha, NE.
authors.forename: Gang
authors.initials: G
authors.lastname: Zhao
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center College of Pharmacy, Omaha, NE.
authors.forename: Xiaobei
authors.initials: X
authors.lastname: Wang
authors.affiliation: Private practice, Canton, SD.
authors.forename: Laura
authors.initials: L
authors.lastname: Pranke
authors.affiliation: Department of Oral Biology, University of Nebraska Medical Center College of Dentistry.
authors.forename: Marian J
authors.initials: MJ
authors.lastname: Schmid
authors.affiliation: Department of Pharmaceutical Sciences, University of Nebraska Medical Center College of Pharmacy, Omaha, NE.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Surgical Specialties, University of Nebraska Medical Center College of Dentistry, Lincoln, NE.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Reinhardt
mesh_terms: D016301:Alveolar Bone Loss; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D005260:Female; D010518:Periodontitis / Q000188:drug therapy*; D011355:Prodrugs / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use*; D055114:X-Ray Microtomography
chemical_list: D000924:Anticholesteremic Agents; D011355:Prodrugs; D019821:Simvastatin
keywords: Histology; hydroxymethylglutaryl-coa reductase inhibitors; micelles; periodontitis; x-ray microtomography