Sustained Efficacy of Erythropoietin with a Hydroxyapatite Carrier Administered in Mice
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概要
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For chronic kidney disease patients with renal anemia, recombinant human erythropoietin (rHuEPO) is a very effective drug; however, the treatment regime is troublesome, requiring multiple administrations each week. In the present study, we examined the efficiency of hydroxyapatite (HAp) as a drug delivery carrier for the sustained release of erythropoietin (EPO) to reduce the frequency of administration. Spray-dried HAp microparticles, formed from zinc-containing HAp (Zn-HAp) and Zn-HAp calcined at 400°C, were used as carriers of EPO, and five Zn-HAp formulation samples incorporating EPO were prepared; no formulation, poly-L-lactic acid (PLA) formulation, zinc (Zn) formulation, Zn/PLA formulation, and calcined/Zn/PLA formulation. ICR mice were administered these samples or commercial rHuEPO (Epogin) as a control from dorsal neck subcutaneous, and hematological and histopathological analyses, including enzyme-linked immunosorbent assay for plasma EPO concentration, were performed. An increase in the blood EPO level was detected on days 3 and 8 post-administration. Peak hematopoiesis was delayed and higher hematological values were obtained on day 14 post-administration with no serious adverse reactions compared with the control. The Zn/PLA formulation sample was found to be most effective in reducing the initial peak while sustaining the delayed release of EPO. In conclusion, the Zn-HAp formulation samples were considered to be useful carriers for the sustained release of EPO, and the Zn/PLA formulation appears to be the most effective of five Zn-HAp formulation samples in sustaining EPO release.
- 社団法人 日本獣医学会の論文
著者
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ITO Shigeo
Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University
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Tanaka Junzo
Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology, Graduate School
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Ito Shigeo
Laboratory Of Pharmacology Department Of Biomedical Sciences Graduate School Of Veterinary Medicine
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Agui Takashi
Laboratory Of Laboratory Animal Science And Medicine Department Of Disease Control Graduate School O
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Tanaka Junzo
Department Of Metallurgy And Ceramics Science Tokyo Institute Of Technology
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SASAKI Nobuya
Laboratory of Experimental Animal Science, Graduate School of Veterinary Medicine, Hokkaido Universi
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Ikoma Toshiyuki
Biomaterials Center, National Institute for Materials Science
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NAGASAKI Ken-ichi
Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School
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KATSUDA Shin-ichi
Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories
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TONEGAWA Toru
Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology
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NAKAMURA Teppei
Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories
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SATO Hidetaka
Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories
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Ikoma Toshiyuki
Biomaterials Center National Institute For Materials Science
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Tanaka Junzo
Department Of Metallurgy And Ceramics Science Graduate School Of Engineering Tokyo Institute Of Tech
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Tanaka Junzo
Department of Inorganic Materials, Tokyo Institute of Technology
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TANAKA Junzo
Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology
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