title: Bisphosphonate release profiles from magnetite microspheres.
abstract: Hyperthermia has been suggested as a novel, minimally invasive cancer treatment method. After implantation of magnetic nano- or microparticles around a tumour through blood vessels, irradiation with alternating magnetic fields facilitates the efficient in situ hyperthermia even for deep-seated tumours. On the basis of this idea, if the microspheres are capable of delivering drugs, they could be promising multifunctional biomaterials effective for chemotherapy as well as hyperthermia. In the present study, magnetite microspheres were prepared by aggregation of the iron oxide colloid in water-in-oil (W/O) emulsion. The release behaviour of alendronate, a typical bisphosphonate, from the microspheres was examined in vitro as a model of the bone tumour prevention and treatment system. The alendronate was successfully incorporated onto the porous magnetite microspheres in vacuum conditions. The drug-loaded microspheres maintained their original spherical shapes even after shaking in ultrapure water for 3 days, suggesting that they have sufficient mechanical integrity for clinical use. It was attributed to high aggregation capability of the magnetite nanoparticles through van der Waals and weak magnetic attractions. The microspheres showed slow release of the alendronate in vitro, resulting from tight covalent or ionic interaction between the magnetite and the alendronate. The release rate was diffusion-controlled type and well controlled by the alendronate concentration in drug incorporation to the microspheres.
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu, Japan tmiya@life.kyutech.ac.jp.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Frontier Research Academy for Young Researchers, Kyushu Institute of Technology, Kitakyushu, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Shirosaki
authors.affiliation: Graduate School of Biomedical Engineering, Tohoku University, Sendai, Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kawashita
authors.affiliation: Faculty of Medicine, Mie University, Tsu, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Matsubara
authors.affiliation: Faculty of Medicine, Mie University, Tsu, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Matsumine
mesh_terms: D019386:Alendronate / Q000008:administration & dosage; D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D001859:Bone Neoplasms / Q000517:prevention & control / Q000628:therapy; D004164:Diphosphonates / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D052203:Ferrosoferric Oxide; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods; D058185:Magnetite Nanoparticles / Q000648:ultrastructure; D008422:Materials Testing; D008863:Microspheres; D008954:Models, Biological; D010316:Particle Size
chemical_list: D001672:Biocompatible Materials; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D019386:Alendronate; D052203:Ferrosoferric Oxide
keywords: Magnetite microspheres; alendronate; bone tumour; drug delivery; slow release