Layer-by-layer polyelectrolyte films containing insulin for pH-triggered release
Layer-by-layer polyelectrolyte films containing insulin for pH-triggered release
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DOI：
10.1039/b918226h
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发表时间：
2010-01-01
影响因子：
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通讯作者：
Anzai, Jun-ichi
中科院分区：
文献类型：
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作者：
Yoshida, Kentaro;Sato, Katsuhiko;Anzai, Jun-ichi
采用逐层沉积的方法制备了含胰岛素的聚电解质薄膜，并对其pH触发释放进行了研究。利用带正电荷的胰岛素和聚阴离子之间的静电引力，在酸性溶液(pH 1.0~3.0)中交替沉积胰岛素和聚硫酸乙烯酯(PVS)、聚丙烯酸(PAA)或硫酸葡聚糖(DS)，成功地制备了含胰岛素的LBL薄膜。膜中胰岛素的负载量取决于所使用的聚阴离子的类型，当以PAA为聚阴离子时，胰岛素负载量最高。在弱酸性(pH 5.0-6.0)或中性(pH 7.4)溶液中，由于胰岛素与聚阴离子之间的静电引力丧失，含有胰岛素的LBL薄膜发生分解，这是由于胰岛素在弱酸性或中性介质中电荷从正电荷反转到负电荷所致。因此，胰岛素在中性或弱酸性的pH值下从LBL膜中释放出来。圆二色谱(CD)表明，释放的胰岛素保持其原有的二级结构。研究发现，即使在pH为1.4(胃pH)的消化酶(胃蛋白酶)存在下，含有胰岛素的LBL膜也是令人满意的稳定的。因此，含胰岛素的LBL膜在未来的胰岛素口服给药中具有潜在的应用前景。
Layer-by-layer (LbL) deposited polyelectrolyte thin films containing insulin were prepared and the pH-triggered release of insulin was studied. Insulin-containing LbL films were successfully prepared by the alternate deposition of insulin and poly(vinyl sulfate) (PVS), poly(acrylic acid) (PAA), or dextran sulfate (DS) in acidic solutions (pH 1.0-3.0) through the electrostatic forces of attraction between positively-charged insulin and polyanions. The loading of insulin in the film was dependent on the type of polyanions used and the highest insulin loading was observed when PAA was used as the polyanion. Insulin-containing LbL films were decomposed when the films were exposed to weakly acidic (pH 5.0-6.0) or neutral solutions (pH 7.4) due to a loss of electrostatic forces of attraction between the insulin and polyanions in the films, which in turn was caused by the charge reversal of insulin from positive to negative in the weakly acidic or neutral media. Thus, insulin is released from LbL films at a neutral or weakly acidic pH. Circular dichroism (CD) spectroscopy revealed that the released insulin retains its original secondary structure. The insulin-containing LbL films were found to be satisfactorily stable even in the presence of a digestive enzyme (pepsin) at pH 1.4 (stomach pH). Consequently, the potential use of the insulin-containing LbL films is suggested for future application in the oral delivery of insulin.