Locally delivered lovastatin nanoparticles enhance fracture healing in rats

Statins stimulate bone formation in vitro and in vivo and, when given in large doses or by prolonged infusions, stimulate biomechanical strength of murine long bones with healing fractures. However, administration of statins by large oral doses or prolonged infusions to a fracture site is not a feas...

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Bibliographic Details
Published in:Journal of orthopaedic research 2007-10, Vol.25 (10), p.1351-1357
Main Authors: Garrett, I.R., Gutierrez, G.E., Rossini, G., Nyman, J., McCluskey, B., Flores, A., Mundy, G.R.
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Anticholesteremic Agents - administration & dosage
bone formation
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Delivery Systems
Female
Femoral Fractures - diagnostic imaging
Femoral Fractures - drug therapy
Femoral Fractures - pathology
Fracture Healing - drug effects
HMG-CoA reductase inhibitors
lovastatin
Lovastatin - administration & dosage
Mice
Mice, Inbred ICR
nanoparticles
Nanoparticles - administration & dosage
Nanoparticles - ultrastructure
Organ Culture Techniques
Osteogenesis - drug effects
Osteogenesis - physiology
Radiography
Rats
Rats, Sprague-Dawley
Skull - drug effects
Skull - pathology
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Summary:Statins stimulate bone formation in vitro and in vivo and, when given in large doses or by prolonged infusions, stimulate biomechanical strength of murine long bones with healing fractures. However, administration of statins by large oral doses or prolonged infusions to a fracture site is not a feasible therapeutic approach to hasten healing of human fractures. We administered lovastatin in biodegradable polymer nanobeads of poly(lactic‐co‐glycolide acid) to determine if lovastatin delivered in low doses in nanoparticles of a therapeutically acceptable scaffold could increase rates of healing in a standard preclinical model of femoral fracture. We found that these nanobeads: (1) stimulated bone formation in vitro at 5 ng/mL, (2) increased rates of healing in femoral fractures when administered as a single injection into the fracture site, and (3) decreased cortical fracture gap at 4 weeks as assessed by microcomputed tomography. These preclinical results suggest that lovastatin administered in a nanobead preparation may be therapeutically useful in hastening repair of human fractures. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:1351–1357, 2007
ISSN:0736-0266
1554-527X
DOI:10.1002/jor.20391