title: Polyphosphoester-based Paclitaxel Complexes: Biological Evaluation.
abstract: BACKGROUND
  Polymer drug delivery systems designed to reduce systemic side-effects are clinically important. Polyphosphoesters are biodegradable polymers with versatile structure that could afford reactive sites or polar functions for drug immobilization.
  
  
  METHODS
  The drug-polyphosphester systems were characterized by nuclear magnetic resonance and infrared spectroscopy, differential scanning calorimetry and dynamic light scattering. In vitro and in vivo experiments were performed to assess the biological activity of the immobilized drug.
  
  
  RESULTS
  Two water-soluble polyphosphoester-based delivery systems of paclitaxel were synthesized. The conjugate with paclitaxel covalently bonded to the polymer, had attenuated activity in vitro. The second system comprised of macromolecular aggregates incorporating the drug via hydrogen bonding. The physical complex achieved a certain level of antitumor activity in vivo and no decrease of body weight - evidence for reduction of the systemic toxic effect associated with paclitaxel treatment.
  
  
  CONCLUSIONS
  The physical complex was found to be a promising carrier for delivery of toxic anticancer agents, e.g. paclitaxel.
authors.affiliation: Faculty of Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan Center for Physical Pharmaceutics, Research Institute for Science and Technology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan Center for Drug Delivery Research, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirota
authors.affiliation: Department of Medico-biological Sciences, Faculty of Dental Medicine, Medical University-Varna, Varna, Bulgaria.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Hristova
authors.affiliation: Institute of Polymers, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Violeta
authors.initials: V
authors.lastname: Mitova
authors.affiliation: Faculty of Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Koda
authors.affiliation: Faculty of Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fushimi
authors.affiliation: Faculty of Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Kuniya
authors.affiliation: Faculty of Pharmaceutical Science, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan Center for Physical Pharmaceutics, Research Institute for Science and Technology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan Center for Drug Delivery Research, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Makino
authors.affiliation: Center for Physical Pharmaceutics, Research Institute for Science and Technology, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan Center for Drug Delivery Research, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan Research Institute for Healthy Living, Niigata University of Pharmacy and Applied Life Sciences, Akiha-ku, Niigata, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terada
authors.affiliation: Department of Medico-biological Sciences, Faculty of Dental Medicine, Medical University-Varna, Varna, Bulgaria.
authors.forename: Rumyana
authors.initials: R
authors.lastname: Cherkezova
authors.affiliation: Department of Materials Science and Chemistry, University of Hyogo, Himeji, Hyogo, Japan.
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yusa
authors.affiliation: Institute of Polymers, Bulgarian Academy of Sciences, Sofia, Bulgaria koseva@polymer.bas.bg.
authors.forename: Neli
authors.initials: N
authors.lastname: Koseva
authors.affiliation: Institute of Polymers, Bulgarian Academy of Sciences, Sofia, Bulgaria.
authors.forename: Kolio
authors.initials: K
authors.lastname: Troev
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004952:Esters; D006801:Humans; D008810:Mice, Inbred C57BL; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004952:Esters; D011108:Polymers; D017239:Paclitaxel
keywords: Paclitaxel; anticancer activity; drug–polymer complex; poly(oxyethylene phosphate)