title: In vivo model to measure bone repair efficacy of nanoparticle-based drug delivery.
abstract: Bone repair required for successful arthroplasty can be compromised in patients with comorbid conditions, such as osteoporosis, diabetes mellitus, and chronic kidney disease. Biological compounds have been proposed to promote bone health and repair. The authors have designed a new animal model for testing bone promoting compounds in the in vivo environment. For initial validation of this model, they used a synthetic agonist of a nuclear receptor, liver X receptor, which has been postulated to play a regulatory role in modulating bone growth. A distal femoral unicortical osteotomy was surgically created on skeletally mature C57Bl/6 male and female mice. A nanoparticle carrier delivery system was used to directly introduce N,N-dimethyl-3β-hydroxycholenamide into the osteotomy. At 35 days post-procedure, the femora were harvested and specimens were obtained for histologic processing and qualitative analysis. The results indicate that the carrier nanoparticles entered the osteotomy defect. Results also indicate that bone repair occurred, although significant differences between groups were not detected in the current study. This study validates the mouse model for testing bone repair promoting compounds. This model can be combined with transgenic or other mouse models to simulate problematic bone repair environments, can be used with a variety of drug carriers, and can test many types of interventional compounds to evaluate potential orthopedic therapeutic applications.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Ackerson
authors.forename: Laura C
authors.initials: LC
authors.lastname: Shum
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Berry
authors.forename: Allan L
authors.initials: AL
authors.lastname: Bucknell
authors.forename: Karen B
authors.initials: KB
authors.lastname: King
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002793:Cholic Acids / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000601:surgery; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules; D057093:Orphan Nuclear Receptors / Q000819:agonists; D010027:Osteotomy
chemical_list: D002793:Cholic Acids; D036341:Intercellular Signaling Peptides and Proteins; D000071518:Liver X Receptors; C413890:N,N-dimethyl-3-hydroxy-5-cholenamide; D053769:Nanocapsules; D057093:Orphan Nuclear Receptors