Insulin-containing layer-by-layer films deposited on poly(lactic acid) microbeads for pH-controlled release of insulin.
Insulin-containing layer-by-layer films deposited on poly(lactic acid) microbeads for pH-controlled release of insulin.
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DOI：
10.1016/j.colsurfb.2011.09.023
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
Ryosuke Hashide;Kentaro Yoshida;Y. Hasebe;Shigehiro Takahashi;Katsuhiko Sato;J. Anzai
中科院分区：
文献类型：
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作者：
Ryosuke Hashide;Kentaro Yoshida;Y. Hasebe;Shigehiro Takahashi;Katsuhiko Sato;J. Anzai
在可生物降解的聚乳酸微球表面沉积了含胰岛素的层层薄膜，并研究了pH触发胰岛素的释放。利用带正电荷的胰岛素与聚阴离子之间的静电引力，在pH值为4.0的条件下，胰岛素与聚硫酸乙烯酯(PVS)或葡聚糖硫酸盐(DS)交替沉积，成功地制备了LBL薄膜。胰岛素在微球上的负载量取决于胰岛素层数和所使用的聚阴离子的类型；膜越厚，当使用PVS作为聚阴离子时，观察到较高的胰岛素负载量。当微球暴露在中性溶液(pH 7.4)中时，胰岛素从微球中释放出来，这是由于胰岛素与薄膜中的聚阴离子之间失去了静电吸引，而这又是由于胰岛素在中性介质中从正电荷反转到负电荷造成的。胰岛素释放的pH阈值为pH 5.0-6.0。圆二色谱表明，释放的胰岛素保留了原有的二级结构。即使在pH 1.5的消化酶(胃酶)存在的情况下，负载在微球上的胰岛素也是令人满意的稳定的。这些结果表明，胰岛素微球在胰岛素口服给药中具有潜在的应用前景。
Layer-by-layer (LbL) thin films containing insulin were deposited on the surface of biodegradable poly(lactic acid) (PLA) microbeads and the pH-triggered release of insulin was studied. The LbL films were successfully prepared by the alternate deposition of insulin and poly(vinyl sulfate) (PVS) or dextran sulfate (DS) at pH 4.0 through the electrostatic force of attraction between positively charged insulin and polyanions. The loading of insulin on the microbeads was dependent on the number of insulin layers and the type of polyanions used; higher insulin loading was observed for thicker films and when PVS was used as the polyanion. Insulin was released from the microbeads when they were exposed to neutral solution (pH 7.4) due to a loss of electrostatic 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 neutral medium. The pH threshold for insulin release was found to be pH 5.0–6.0. The released insulin retained its original secondary structure as evidenced by circular dichroism spectra. The insulin loaded on the microbeads was satisfactorily stable even in the presence of a digestive enzyme (pepsin) at pH 1.5. These results suggest a potential future use for insulin-loaded microbeads in the oral delivery of insulin.