title: Hydroxyapatite nanoparticles: preparation, characterization, and evaluation of their potential use in bone targeting: an animal study.
abstract: OBJECTIVE
  Hydroxyapatite is used as a drug-delivery system for bone therapy applications because of its biocompatibility, bioactivity, and osteoconductive properties. In addition, hydroxyapatite nanoparticles (HApN) might be used as a theranostic probe. The aim of this study was to prepare and characterize hydroxyapatite mesoporous nanoparticles, and radiolabel these nanoparticles with technetium-99m (Tc). Moreover, biodistribution studies were carried out in healthy mice.
  
  
  METHODS
  HApN were synthesized and characterized. Tc-HApN was prepared by adding Tc-pertechnetate to a dispersion of HApN in the presence of stannous chloride. Radiochemical purity and in-vitro stability were determined. The circulation time of Tc-HApN was determined by measuring blood radioactivity in healthy mice. In addition, biodistribution studies were carried out in healthy mice at 1 and 4 h after injection.
  
  
  RESULTS
  Tc-HApN showed high radiochemical purity (98.7±0.2%) and in-vitro stability until 24 h. Tc-HApN levels in blood decreased in a biphasic manner, with an α half-life of 1.8 min and a β half-life of 126.9 min. High uptake was achieved in the liver and spleen because of the macrophage uptake. Furthermore, bone uptake was higher than that of the surrounding muscle, resulting in high bone-to-muscle ratios.
  
  
  CONCLUSIONS
  HApN were synthesized successfully with suitable characteristics for in-vivo applications. Tc-HApN was prepared and showed high stability. Tc-HApN presented increasing bone uptake over time, showing a higher affinity to bone tissues in contrast to surrounding muscle. The present results, together with further studies, may indicate a potential application of HApN as a nanocarrier for bone diseases.
authors.affiliation: aDepartment of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte bDepartment of Chemistry and Mathematics, Institute of Science, Laboratory of Bioengineering, Federal University of Itajubá, Itabira, Minas Gerais, Brazil cDepartment of Biomedical Engineering, University of Wisconsin-Madison, Madison, Wisconsin, USA dDepartment of Nuclear Medicine, Radiology, NeuroRadiology, Medical Physics, Clinical Laboratory, Microbiology, Pathology, Santa Maria della Misericordia Hospital, Rovigo, Italy.
authors.forename: Ana Luiza C
authors.initials: AL
authors.lastname: Maia
authors.forename: Carolina H
authors.initials: CH
authors.lastname: Cavalcante
authors.forename: Marina G F de
authors.initials: MG
authors.lastname: Souza
authors.forename: Carolina de A
authors.initials: Cde A
authors.lastname: Ferreira
authors.forename: Domenico
authors.initials: D
authors.lastname: Rubello
authors.forename: Sotirios
authors.initials: S
authors.lastname: Chondrogiannis
authors.forename: Valbert N
authors.initials: VN
authors.lastname: Cardoso
authors.forename: Gilson A
authors.initials: GA
authors.lastname: Ramaldes
authors.forename: André L B de
authors.initials: AL
authors.lastname: Barros
authors.forename: Daniel C F
authors.initials: DC
authors.lastname: Soares
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000378:metabolism*; D015195:Drug Design; D004355:Drug Stability; D017886:Durapatite / Q000737:chemistry* / Q000493:pharmacokinetics*; D005240:Feasibility Studies; D007553:Isotope Labeling; D008657:Metabolic Clearance Rate; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009928:Organ Specificity; D010316:Particle Size; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D013667:Technetium / Q000737:chemistry* / Q000493:pharmacokinetics; D000068936:Theranostic Nanomedicine / Q000379:methods; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: D019275:Radiopharmaceuticals; D013667:Technetium; D017886:Durapatite