Self-dissolving microneedles for the percutaneous absorption of EPO in mice.
Erythropoietin (EPO) loaded microneedles were prepared using thread-forming polymer as a base for the percutaneous administration of EPO. The used polymers were dextrin, chondroitin sulfate and albumin. Under room temperature, EPO solution was added to high concentration of polymer solution and microneedles were prepared by forming thread with polypropylene tips. The mean weight of microneedle was 0.59 +/- 0.01 mg and length and basal diameter were 3.24 +/- 0.16 and 0.55 +/- 0.03 mm, respectively. Four microneedles were percutaneously (pc) administered to mice at the EPO dose levels of 100 IU/kg. After administration, blood samples were collected for 24 h and serum EPO levels were measured. Dextrin EPO microneedles were administered both pc and subcutaneously (sc) to mice. Serum EPO levels vs. time profiles showed Cmax of 138.6 +/- 16.1 and 146.5 +/- 8.0 mIU/ml, respectively. Tmax were 7.5 h. The values of bioavailability (BA) of EPO were 82.1 and 99.4%, respectively. By decreasing the dose from 100 to 50 and 25 IU/kg, dose-dependent serum EPO levels vs. time profiles were not clearly obtained. When chondroitin sulfate and albumin were used as the microneedle base, the serum EPO levels vs. time profiles showed almost the same pattern. Cmax of chondroitin sulfate and albumin microneedles were 96.3 +/- 8.8 and 132.2 +/- 18.9 mIU/ml, respectively. AUCs were 835.1 and 1098.7 mIU h/ml. Tmax were 8 and 6.8 h. These results suggest the usefulness of microneedles for the percutaneous administration of EPO.
Ito
Yukako
Y
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-Ku, Kyoto, 607-8414, Japan. yukako@mb.kyoto-phu.ac.jp
Yoshimitsu
Jun-Ichiro
J
Shiroyama
Keiji
K
Sugioka
Nobuyuki
N
Takada
Kanji
K
D000418:Albumins / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical; D002809:Chondroitin Sulfates / Q000737:chemistry; D003912:Dextrins / Q000737:chemistry; D004921:Erythropoietin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D051379:Mice; D012869:Skin Absorption
D000418:Albumins; D003912:Dextrins; D004921:Erythropoietin; D002809:Chondroitin Sulfates