Amelioration of Anemia in the ICGN Mouse, a Renal Anemia Model, with a Subcutaneous Bolus Injection of Erythropoietin Adsorbed to Hydroxyapatite Matrix

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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.