自组装 pH 敏感胆甾醇 pullulan 纳米凝胶作为蛋白质递送载体。

Self-assembled pH-sensitive cholesteryl pullulan nanogel as a protein delivery vehicle.

机构信息

Department of Materials Processing, Graduate School of Engineering, Tohoku University, 6-6-02 Aramaki-aza Aoba, Aoba-ku, Sendai 980-8579, Japan.

出版信息

Biomacromolecules. 2013 Jan 14;14(1):56-63. doi: 10.1021/bm301286h. Epub 2012 Dec 21.

A self-assembled nanogel, derived from an acid-labile cholesteryl-modified pullulan (acL-CHP), was prepared by grafting vinyl ether-cholesterol substituents onto a 100 kD pullulan main chain polymer backbone. Stable nanogels are formed by acL-CHP self-assemblies at neutral pH. The hydrodynamic radius of the nanogels, observed to be 26.5 ± 5.1 nm at pH 7.0, increased by ~135% upon acidification of the solution to pH 4.0. SEC analysis of the acL-CHP nanogel at pH 4.0 showed that the grafts were nearly 80% degraded after 24 h, whereas little or no degradation was observed over the same time period for a pH stable analog (acS-CHP) at pH 4.0 or the acL-CHP at pH 7.0. Complexation of BSA with the acL-CHP nanogel was observed at pH 7.0 with subsequent release of the protein upon acidification. These findings suggest that stimuli-responsive, self-assembled nanogels can release protein cargo in a manner that is controlled by the degradation rate of the cholesterol-pullulan grafting moiety.

一种自组装纳米凝胶，由酸敏感的胆甾醇修饰的支链淀粉（acL-CHP）衍生而来，是通过将乙烯醚-胆固醇取代基接枝到 100 kD 支链淀粉主链聚合物骨架上制备的。在中性 pH 下，acL-CHP 自组装形成稳定的纳米凝胶。纳米凝胶的流体力学半径在 pH 7.0 时观察到为 26.5 ± 5.1nm，当溶液酸化至 pH 4.0 时增加了约 135%。在 pH 4.0 下对 acL-CHP 纳米凝胶进行 SEC 分析表明，在 24 小时后接枝物几乎降解了 80%，而在相同时间内，pH 稳定类似物（acS-CHP）在 pH 4.0 或 pH 7.0 下的 acL-CHP 几乎没有或没有降解。在 pH 7.0 下观察到 BSA 与 acL-CHP 纳米凝胶的络合，随后在酸化时释放蛋白质。这些发现表明，刺激响应的自组装纳米凝胶可以以胆固醇-支链淀粉接枝部分的降解速率控制的方式释放蛋白质货物。