title: Locally delivered lovastatin nanoparticles enhance fracture healing in rats.
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.
authors.affiliation: OsteoScreen Ltd., 2040 Babcock Road, San Antonio, Texas 78023, USA.
authors.forename: I R
authors.initials: IR
authors.lastname: Garrett
authors.forename: G E
authors.initials: GE
authors.lastname: Gutierrez
authors.forename: G
authors.initials: G
authors.lastname: Rossini
authors.forename: J
authors.initials: J
authors.lastname: Nyman
authors.forename: B
authors.initials: B
authors.lastname: McCluskey
authors.forename: A
authors.initials: A
authors.lastname: Flores
authors.forename: G R
authors.initials: GR
authors.lastname: Mundy
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D005264:Femoral Fractures / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D017102:Fracture Healing / Q000187:drug effects*; D008148:Lovastatin / Q000008:administration & dosage*; D051379:Mice; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D012886:Skull / Q000187:drug effects / Q000473:pathology
chemical_list: D000924:Anticholesteremic Agents; D008148:Lovastatin