Amelioration of anemia in the ICGN mouse, a renal anemia model, with a subcutaneous bolus injection of erythropoietin adsorbed to hydroxyapatite matrix.
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.
Nagasaki
Ken-Ichi
K
Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Hokkaido University, Kita-18, Nishi-9, Kita-ku, Sapporo 060-0818, Japan.
Ikoma
Toshiyuki
T
Katsuda
Shin-Ichi
S
Tonegawa
Toru
T
Tanaka
Junzo
J
Ohyama
Minami
M
Hayashida
Kosuke
K
Nakamura
Teppei
T
Sato
Hidetaka
H
Ito
Shigeo
S
Sasaki
Nobuya
N
Agui
Takashi
T
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
D003692:Delayed-Action Preparations; D011994:Recombinant Proteins; D004921:Erythropoietin; D017886:Durapatite