Self-Dissolving Micropile Array Chip as Percutaneous Delivery System of Protein Drug
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概要
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Erythropoietin (EPO) was successfully loaded on self-dissolving micropile array (SDMA) chip using chondroitin sulfate as the base polymer. “Drug glue” was prepared by adding EPO solution to chondroitin sulfate solution and SDMA was formed by micromolding fabrication technology. One SDMA chip, 1.0×1.0 cm, contained 100 micropile arrays. Two types of SDMA, partially-loaded SDMA (p-SDMA) and fully-loaded SDMA (f-SDMA), were prepared. The mean lengths of the SDMAs were 474.8±8.1 μm for p-SDMA and 473.4±5.2 μm for f-SDMA. The diameters of the array basements were 288.4±4.5 μm (p-SDMA) and 294.6±3.2 μm (f-SDMA). EPO content was 25.0±3.8 IU (p-SDMA) and 125.9±26.7 IU (f-SDMA). After percutaneous administration of each SDMA chip to rats, maximum serum EPO concentrations (Cmax) were 30.5±4.2 mIU/ml for p-SDMA and 32.4±5.0 mIU/ml for f-SDMA. The mean areas under the serum EPO concentration vs. time curves (AUC) were 534.0±102.4 mIU·h/ml (p-SDMA) and 523.1±50.4 mIU·h/ml (f-SDMA). Bioavailability (BA) values of EPO delivered from SDMAs were calculated to be 39.4% for p-SDMA and 7.7% for f-SDMA. Dose-dependency of the serum EPO concentration vs. time curve was studied using p-SDMA chip containing less EPO, 11.6±1.06 IU. Good dose-dependency was observed for Cmax and AUC. The p-SDMA chip was also evaluated in dogs. One or two p-SDMA chips, where 1 chip contained 22.4 IU of EPO, were percutaneously administered to dogs. BA of EPO delivered from p-SDMA was 65.9—69.0%. These results suggest the usefulness of p-SDMA as a percutaneous drug delivery system (DDS) for EPO.
著者
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SUGIOKA Nobuyuki
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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FUKUSHIMA Keizo
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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TAKADA Kanji
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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ITO Yukako
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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Takada Kanji
Department Of Biopharmaceutics Kyoto Pharmaceutical University:exploratory Development Laboratories
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Fukumoto Kyoko
Department Of Pharmacokinetics Kyoto Pharmaceutical University
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Hasegawa Ryo
Department Of Information And Computer Science Keio University
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Hasegawa Ryo
Department of Pharmacokinetics, Kyoto Pharmaceutical University
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HASEGAWA Ryo
Department of Electrical and Electronic Engineering, Tokyo Institute of Technology
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Hasegawa Ryo
Department of Chemistry, Faculty of Science and Technology, Sophia University
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ITO Yukako
Department of Dermatology and Plastic Surgery, Head & Neck Surgery
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