Graduate School of Pharmaceutical Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
Colloids Surf B Biointerfaces. 2012 Jan 1;89:242-7. doi: 10.1016/j.colsurfb.2011.09.023. Epub 2011 Sep 18.
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.
通过正电荷胰岛素与聚阴离子之间的静电吸引力，在 pH 值为 4.0 时，成功地将胰岛素和聚硫酸乙烯（PVS）或硫酸葡聚糖（DS）交替沉积在可生物降解的聚乳酸（PLA）微球表面，制备了层状（LbL）薄膜，并研究了胰岛素的 pH 触发释放。微球上的胰岛素负载取决于胰岛素层的数量和所使用的聚阴离子的类型；当使用 PVS 作为聚阴离子时，观察到较厚的薄膜具有更高的胰岛素负载。当微球暴露于中性溶液（pH 7.4）时，由于薄膜中胰岛素和聚阴离子之间的静电吸引力丧失，胰岛素从微球中释放出来，这反过来又导致胰岛素在中性介质中从正电荷变为负电荷，从而发生电荷反转。发现胰岛素释放的 pH 阈值为 pH 5.0-6.0。释放的胰岛素保留了其原始的二级结构，这可以通过圆二色性光谱证明。即使在 pH 值为 1.5 时存在消化酶（胃蛋白酶），负载在微球上的胰岛素也能保持令人满意的稳定性。这些结果表明，载有胰岛素的微球在胰岛素的口服递送中具有潜在的未来用途。
