title: Amelioration of anemia in the ICGN mouse, a renal anemia model, with a subcutaneous bolus injection of erythropoietin adsorbed to hydroxyapatite matrix.
abstract: The recombinant human erythropoietin (rhEPO) is used for the treatment of patients with renal anemia. However, rhEPO should be administered subcutaneously or intravenously three times a week. The repetitive injections of rhEPO result in burdens to patients. To resolve this problem, we investigated the sustaining release methods using an rhEPO-hydroxyapatite (HAp) made by spray-drying technique as the drug delivery system. Two types of rhEPO-HAp formulations were prepared; zinc (Zn) formulation and Zn and poly-L-lactic acid (PLA) formulation. These formulations were examined in genetically anemic model, ICGN (ICR-derived glomerulonephritis) mice. According to in vivo release test of rhEPO from HAp in ICGN mice, elevated plasma concentration of rhEPO could be maintained for more than 7 days. These mice showed the amelioration of anemia for more than 3 weeks post-administration without causing any side effect. In conclusion, Zn or Zn/PLA formulation of HAp was considered to be one of the useful carriers of rhEPO for long-term improvement of anemia.
authors.affiliation: Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Hokkaido University, Kita-18, Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Nagasaki
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ikoma
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Katsuda
authors.forename: Toru
authors.initials: T
authors.lastname: Tonegawa
authors.forename: Junzo
authors.initials: J
authors.lastname: Tanaka
authors.forename: Minami
authors.initials: M
authors.lastname: Ohyama
authors.forename: Kosuke
authors.initials: K
authors.lastname: Hayashida
authors.forename: Teppei
authors.initials: T
authors.lastname: Nakamura
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Sato
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ito
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sasaki
authors.forename: Takashi
authors.initials: T
authors.lastname: Agui
mesh_terms: D000740:Anemia / Q000188:drug therapy*; D000818:Animals; D003692:Delayed-Action Preparations; D017886:Durapatite / Q000737:chemistry*; D004921:Erythropoietin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D005921:Glomerulonephritis / Q000150:complications / Q000188:drug therapy; D006801:Humans; D051379:Mice; D008815:Mice, Inbred Strains; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D004921:Erythropoietin; D017886:Durapatite