クラスターデキストリンの体内動態研究―生分解性高分子担体としての利用性―

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  • Biodisposition of Cluster Dextrin as a Biodegradable Drug Carrier

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<p>Cluster dextrinTM (CDex, Highly-branched cyclic dextrin) produced from starch is a glucose polymer which has a cyclic structure in the molecule. Despite its large molecular weight (462 kDa), CDex is highly water-soluble and easily digested with enzymes such as α-amylase. First, the hydroxyl group of the sugar ring of CDex was reacted with octamethylenediamine (OMD) by the 1, 1'-carbonyldiimidazole (CDI) activation method. The obtained product (CDex-OMD) was then labeled with FITC via the amino residue of CDex-OMD. A systemic kinetic analysis of FITC-labeled CDex-OMD (CDex-OMD-F) in rats was carried out by using both a spectrofluorometer and specific high-performance size-exclusion chromatography (HPSEC). Intravenously administered CDex-OMD-F was rapidly eliminated from the blood circulation followed by an appreciable excretion into the urine. HPSEC analysis showed that CDex-OMD-F was quickly degraded into small molecules (∼6 kDa) in the blood. On the other hand FITC-labeled CDex (FCDex) was successfully synthesized by the modified method of de Belder and Granath. Sugar hydroxyl groups of the FCDex were partially activated by periodate oxidation in order to acquire the aldehyde groups to which guest molecules can be bound. The rate of enzymatic degradation of FCDex was controlled by the degree of oxidation. It was found that high NaIO4-treatment extended the blood persistence of FCDex injected intravenously. The prolongation of the circulation time resulted in a high liver uptake followed by a marked fecal excretion. It was suggested that CDex is a liver-specific drug carrier whose biodegradability is controllable by attaching a guest molecule by the NaIO4-oxidation method.</p>

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  • 薬剤学

    薬剤学 69 (5), 373-383, 2009

    公益社団法人 日本薬剤学会

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