Hashide Ryosuke, Yoshida Kentaro, Hasebe Yasushi, Seno Masaru, Takahashi Shigehiro, Sato Katsuhiko, Anzai Jun-Ichi
J Nanosci Nanotechnol. 2014 Apr;14(4):3100-5. doi: 10.1166/jnn.2014.8562.
Poly(lactic acid) (PLA) microparticles were coated with layer-by-layer (LbL) films containing insulin and the pH-dependent release of insulin was studied. The LbL films were prepared on the surface of PLA microparticles by the alternate deposition of insulin and poly(allylamine hydrochloride) (PAH) through the electrostatic attraction between insulin and PAH. The insulin loading on the PLA microparticles depended on the film thickness, which corresponded to the number of insulin layers, and on the pH of the solution used to deposit insulin. The insulin loading increased with the film thickness and when the film was prepared at pH 7.4. The LbL films decomposed upon exposure to acidic solutions because the electrostatic attraction between the insulin and the PAH in the films disappeared when the charge on insulin changed from negative to positive at an acidic pH, which resulted in the release of insulin. The temperature and salt concentration did not affect the pH stability of the LbL films. The pH threshold for insulin release was pH 5.0-6.0, which corresponds to isoelectric point of insulin, 5.4. The release of insulin from the microparticles was rapid, and was almost complete within a few minutes. The circular dichroism spectra showed that the released insulin retained its original secondary structure. Our insulin-loaded PLA microparticles may be useful for the controlled release of insulin.
聚乳酸（PLA）微粒被含有胰岛素的层层（LbL）膜包覆，并对胰岛素的pH依赖性释放进行了研究。通过胰岛素与聚（烯丙胺盐酸盐）（PAH）之间的静电吸引，将胰岛素和PAH交替沉积在PLA微粒表面，制备了LbL膜。PLA微粒上的胰岛素负载量取决于膜厚度（这与胰岛素层数相对应）以及用于沉积胰岛素的溶液的pH值。胰岛素负载量随膜厚度增加而增加，且在pH 7.4条件下制备膜时负载量更高。LbL膜在暴露于酸性溶液时会分解，因为在酸性pH下胰岛素电荷从负变为正时，膜中胰岛素与PAH之间的静电吸引消失，导致胰岛素释放。温度和盐浓度不影响LbL膜的pH稳定性。胰岛素释放的pH阈值为pH 5.0 - 6.0，这与胰岛素的等电点5.4相对应。胰岛素从微粒中的释放很快，几分钟内几乎完全释放。圆二色光谱表明，释放的胰岛素保留了其原始二级结构。我们负载胰岛素的PLA微粒可能有助于胰岛素的控释。
