Sustained efficacy of erythropoietin with a hydroxyapatite carrier administered in mice.
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 degrees 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.
Nagasaki
Ken-Ichi
K
Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Japan.
Ikoma
Toshiyuki
T
Katsuda
Shin-Ichi
S
Tonegawa
Toru
T
Tanaka
Junzo
J
Nakamura
Teppei
T
Sato
Hidetaka
H
Ito
Shigeo
S
Sasaki
Nobuya
N
Agui
Takashi
T
D000740:Anemia / Q000097:blood / Q000188:drug therapy*; D000818:Animals; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems / Q000379:methods*; D004906:Erythrocyte Count; D004921:Erythropoietin / Q000008:administration & dosage* / Q000097:blood; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D006882:Hydroxyapatites / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D009929:Organ Size / Q000187:drug effects; D011994:Recombinant Proteins; D013047:Specific Pathogen-Free Organisms
D003692:Delayed-Action Preparations; D006454:Hemoglobins; D006882:Hydroxyapatites; D011994:Recombinant Proteins; D004921:Erythropoietin