Sustained Efficacy of Erythropoietin with a Hydroxyapatite Carrier Administered in Mice

Journal of Veterinary Medical Science

Hidetaka SATO⁴  Nobuya SASAKI³  Shin-ichi KATSUDA⁴  Takashi AGUI³  Toru TONEGAWA¹  Junzo TANAKA¹  Ken-ichi NAGASAKI³  Teppei NAKAMURA⁴  Shigeo ITO²  Toshiyuki IKOMA⁵ 

[1] Department of Metallurgy and Ceramics Science, Tokyo Institute of Technology;Laboratory of Pharmacology, Department of Biomedical Sciences, Graduate School of Veterinary Medicine, Hokkaido University;Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University;Section of Biological Safety Research, Chitose Laboratory, Japan Food Research Laboratories;Biomaterials Center, National Institute for Materials Science

关键词: anemia;    erythropoietin;    hydroxyapatite;    sustained release;   

DOI  :  10.1292/jvms.71.729

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(36)Cited-By(2)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.

【 授权许可】

Unknown