Localized Intermittent Delivery of Simvastatin Hydroxyacid Stimulates Bone Formation in Rats

Background: The cholesterol‐lowering drug simvastatin promotes bone formation in cell cultures and animal models. In previous studies, devices for the controlled, localized delivery of simvastatin hydroxyacid enhanced osteoblastic activity in vitro. The objective of this investigation was to determi...

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Bibliographic Details
Published in:Journal of periodontology (1970) 2008-08, Vol.79 (8), p.1457-1464
Main Authors: Jeon, Ju Hyeong, Piepgrass, Ward T., Lin, Yi‐Ling, Thomas, Mark V., Puleo, David A.
Format: Article
Language:English
Subjects:
Administration, Topical
Animals
Biological and medical sciences
Cellulose - analogs & derivatives
Controlled release
Delayed-Action Preparations
Dentistry
Drug Carriers
Drug Delivery Systems
Hydroxymethylglutaryl CoA Reductases - administration & dosage
Lactic Acid
Male
Medical sciences
Microspheres
Models, Animal
osteogenesis
Osteogenesis - drug effects
Otorhinolaryngology. Stomatology
Polyethylene Glycols
Polyglycolic Acid
Rats
Rats, Sprague-Dawley
simvastatin
Simvastatin - administration & dosage
Simvastatin - analogs & derivatives
simvastatin hydroxyacid
Skull - drug effects
Skull - pathology
sustained release
Time Factors
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Summary:Background: The cholesterol‐lowering drug simvastatin promotes bone formation in cell cultures and animal models. In previous studies, devices for the controlled, localized delivery of simvastatin hydroxyacid enhanced osteoblastic activity in vitro. The objective of this investigation was to determine bioactivity of the delivery system in vivo. Methods: Devices for sustained or intermittent release of simvastatin hydroxyacid were formed using a blend of cellulose acetate phthalate and a poly(ethylene oxide) and poly(propylene oxide) block copolymer, and they were implanted directly over the calvarium of young male rats. Drug‐free devices were used as controls. After 9, 18, or 28 days, specimens were histologically evaluated for new bone formation. Results: All three groups showed some level of new bone formation, but the extent of osteogenesis depended on the type of implant. Devices delivering simvastatin hydroxyacid were associated with a 77.5% to 133% increase in new woven bone thickness compared to control devices without a drug (P
ISSN:0022-3492
1943-3670
DOI:10.1902/jop.2008.080004