title: Controlled Release of Chemotherapeutic Platinum-Bisphosphonate Complexes from Injectable Calcium Phosphate Cements.
abstract: Herein, we present a method to release chemotherapeutic platinum-bisphosphonate (Pt-BP) complexes from apatitic calcium phosphate cements (CPCs). Pt-BP-loaded hydroxyapatite nanoparticles (HA NPs) were added at different ratios to the powder phase of the cements, which contained poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres as porogens to accelerate their degradation. In vitro release kinetics of Pt-BP complexes revealed that the release rate of Pt species can be tuned by varying the amount of drug-loaded HA NPs as well as modifying the chemical structure of the Pt-BP complex to tailor its affinity with HA NPs. In addition, the incorporation of PLGA microspheres into the CPCs increased the degradation rate of the materials without affecting the release rate of Pt species. Finally, the antiproliferative activity of the free Pt-BP complexes and Pt-BP-loaded CPCs was evaluated using both human osteosarcoma cancer cells (MG-63) and human bone marrow-derived mesenchymal stromal cells (h-BMMSCs). This study demonstrated that both free Pt-BP complexes and the releasates from the CPCs were antiproliferative in a dose-dependent manner. Moreover, their antiproliferative activity was higher on MG-63 cells compared to h-BMMSC primary cells. In summary, it was shown that injectable CPCs can be rendered chemotherapeutically active by incorporation of HA NPs loaded with HA-binding Pt-BP complexes.
authors.affiliation: 1 Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Kambiz
authors.initials: K
authors.lastname: Farbod
authors.affiliation: 1 Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Kemal
authors.initials: K
authors.lastname: Sariibrahimoglu
authors.affiliation: 2 Department of Chemistry, Università degli Studi di Bari Aldo Moro , Bari, Italy .
authors.forename: Alessandra
authors.initials: A
authors.lastname: Curci
authors.affiliation: 1 Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Astghik
authors.initials: A
authors.lastname: Hayrapetyan
authors.affiliation: 1 Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Jan N W
authors.initials: JN
authors.lastname: Hakvoort
authors.affiliation: 1 Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Jeroen J J P
authors.initials: JJ
authors.lastname: van den Beucken
authors.affiliation: 3 Institute of Science and Technology for Ceramics (ISTEC) , National Research Council (CNR), Faenza, Italy .
authors.forename: Michele
authors.initials: M
authors.lastname: Iafisco
authors.affiliation: 2 Department of Chemistry, Università degli Studi di Bari Aldo Moro , Bari, Italy .
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.affiliation: 1 Department of Biomaterials, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center , Nijmegen, The Netherlands .
authors.forename: Sander C G
authors.initials: SC
authors.lastname: Leeuwenburgh
mesh_terms: D001843:Bone Cements / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D045744:Cell Line, Tumor; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000494:pharmacology; D004164:Diphosphonates / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D017886:Durapatite / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D053758:Nanoparticles / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D001843:Bone Cements; D003692:Delayed-Action Preparations; D004164:Diphosphonates; D010984:Platinum; D017886:Durapatite