title: In vivo release of the antimicrobial peptide hLF1-11 from calcium phosphate cement.
abstract: We studied the release of human lactoferrin 1-11 (hLF1-11), a potent antimicrobial peptide, in an animal model. Calcium phosphate cement with 50 mg/g hLF1-11 was injected into the femoral canal of 12 rabbits. One, 3, and 7 days later, four animals were terminated, and the femora excised. Sections of bone and cement were removed for histological analysis. We used liquid chromatography-mass spectrometry/mass spectrometry for semiquantitative determination of the hLF1-11 concentration. Blood samples were drawn for leukocyte count and differentiation to identify a potential immunomodulating effect of hLF1-11. After an initial burst release, the hLF1-11 concentration in cement and bone decreased steadily. This in vivo release profile is consistent with earlier in vitro studies. Tissue ingrowth into the cement, without signs of inflammation or necrosis, was observed. Leukocytosis or a shift in leukocyte differentiation did not occur. The carrier released over 99% of the hLF1-11, resulting in peak concentrations at the cement-bone interface. This indicates that hLF1-11 could become a valuable prophylactic agent in osteomyelitis treatment.
authors.affiliation: Department of Orthopaedic Surgery, VU University Medical Center, P.O. Box 7057, Amsterdam, 1007 MB, The Netherlands. hpstallmann@gmail.com
authors.forename: Hein P
authors.initials: HP
authors.lastname: Stallmann
authors.forename: Ronald
authors.initials: R
authors.lastname: de Roo
authors.forename: Chris
authors.initials: C
authors.lastname: Faber
authors.forename: Arie V Nieuw
authors.initials: AV
authors.lastname: Amerongen
authors.forename: Paul I J M
authors.initials: PI
authors.lastname: Wuisman
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage*; D001843:Bone Cements / Q000627:therapeutic use*; D002130:Calcium Phosphates; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D007781:Lactoferrin; D010019:Osteomyelitis / Q000209:etiology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000008:administration & dosage*; D019919:Prosthesis Implantation / Q000009:adverse effects*; D011817:Rabbits
chemical_list: D023181:Antimicrobial Cationic Peptides; D001843:Bone Cements; D002130:Calcium Phosphates; D010446:Peptide Fragments; C466658:lactoferrin (1-11), human; C020243:calcium phosphate; D007781:Lactoferrin