Locally delivered lovastatin nanoparticles enhance fracture healing in rats

I. R. Garrett, G. E. Gutierrez, G. Rossini, J. Nyman, B. McCluskey, A. Flores, G. R. Mundy

Research output: Contribution to journalArticlepeer-review

79 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1351-1357
Number of pages7
JournalJournal of Orthopaedic Research
Volume25
Issue number10
DOIs
StatePublished - Oct 2007
Externally publishedYes

Keywords

  • Bone formation
  • HMG-CoA reductase inhibitors
  • Lovastatin
  • Nanoparticles

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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