ポリ(3-ヒドロキシブチレート)を用いたミクロスフェアの薬物放出速度に関する実験的研究(第2報)
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概要
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The releasing rate of poly(3-hydroxybutyrate)-P(3HB)-microapheres containing Lastet, an anticancer agent, was investigated both <I>in vitro</I> and <I>in vivo</I>. The rate of the release of Lastet from P(3HB) microspheres was very small and only 20% was released during a 15-day period. The addition of acylglycerols to P(3HB) increased the releasing rate of Lastet. P(3HB) microspheres which contained 25% glycerol tristearate (GTS) and 25% glycerol monostearate (MTS) released 100% and 50% of the Lastet during a 10-day period, respectively. In the surface of P (3HB) microspheres without acylglycerol, a number of small holes of 1 <I>μ</I>m diameter were observed. And large holes of 5 <I>μ</I>m diameter were observed in the surface of P(3HB) microspheres with GTS. There was no significant difference in surface property between P(3HB) microspheres with MTS and those without acylglycerol. P (3HB) microspheres which contained 25% MTS and 10% Lastet were administered intraperitoneally to rats and the change of Lastet concentration in blood and tissue was investigated. Although in low levels, Lastet was detected in the blood up to 24hr after administration. And Lastet was detected in high levels in the mediastinal tissue up to day 7. The change of the surface property of microspheres confirmed by scanning electron micrographs suggested that the decomposition of P(3HB) <I>in vivo</I> may be accelerated by some enzyme to increase the release of drugs.
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