Self-dissolving microneedles for the percutaneous absorption of EPO in mice
Self-dissolving microneedles for the percutaneous absorption of EPO in mice
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DOI：
10.1080/10611860600785080
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发表时间：
2006-06-01
影响因子：
4.5
通讯作者：
Takada, Kanji
中科院分区：
文献类型：
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作者：
Ito, Yukako;Yoshimitsu, Jun-Ichiro;Takada, Kanji
以成丝聚合物为基质制备了载红细胞生成素（EPO）微针，用于经皮给药。所用的聚合物是糊精、硫酸软骨素和白蛋白。在室温下，将EPO溶液加入到高浓度聚合物溶液中，通过与聚丙烯尖端形成线来制备微针。微针的平均重量为0.59 +/- 0.01 mg，长度和基部直径分别为3.24 +/- 0.16和0.55 +/- 0.03 mm。以100 IU/kg的EPO剂量水平向小鼠施用四个微针。给药后24 h采血，测定血清EPO水平。将糊精EPO微针pc和皮下（sc）施用至小鼠。血清EPO水平与时间曲线显示C-max分别为138.6 +/- 16.1和146.5 +/- 8.0 mIU/ml。Tmax为7.5 h。EPO的生物利用度（BA）分别为82.1%和99.4%。通过将剂量从100降低至50和25 IU/kg，未明确获得剂量依赖性血清EPO水平与时间曲线。当使用硫酸软骨素和白蛋白作为微针基底时，血清EPO水平与时间曲线显示几乎相同的模式。硫酸软骨素和白蛋白微针的Cmax分别为96.3 +/- 8.8和132.2 +/- 18.9 mIU/ml。AUC为835.1和1098.7 mIU h/ml。Tmax分别为8和6.8 h。这些结果表明微针用于经皮施用EPO的有用性。
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 C-max of 138.6 +/- 16.1 and 146.5 +/- 8.0 mIU/ml, respectively. T-max 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. T-max were 8 and 6.8 h. These results suggest the usefulness of microneedles for the percutaneous administration of EPO.