Engineered Multifunctional Albumin-Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin
Engineered Multifunctional Albumin-Decorated Porous Silicon Nanoparticles for FcRn Translocation of Insulin
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DOI：
10.1002/smll.201800462
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发表时间：
2018-07-05
期刊：
影响因子：
13.3
通讯作者：
Santos, Helder A.
中科院分区：
文献类型：
--
作者：
Martins, Joao P.;D'Auria, Roberto;Santos, Helder A.
在过去的十年中，在药物输送系统的发展方面取得了显著的进展，可以替代以肠外注射为基础的胰岛素输送。新生儿Fc受体（FcRn）介导的胞吞作用最近被认为是增加药物通过肠上皮运输的一种策略。FcRn靶向纳米颗粒（NPs）可以劫持FcRn的转细胞途径并穿过上皮细胞层。在这项研究中，提出了一种基于多孔硅纳米粒子的胰岛素递送纳米颗粒系统。在与白蛋白表面结合并装载胰岛素后，NPs通过纳米沉淀被封装成ph响应聚合物颗粒。所开发的NP配方具有粒径控制和粒径分布均匀的特点。透射电子显微镜（TEM）图像显示NPs成功封装成ph敏感聚合物颗粒。在酸性条件下未检测到胰岛素释放，但在肠道ph值下观察到控释。毒性研究表明NPs与肠细胞具有高相容性。在体外，当胰岛素被装载到fcrn靶向的NPs中时，胰岛素在肠上皮中的渗透表现出大约5倍的增加。总的来说，这些fcrn靶向NPs为口服胰岛素靶向治疗的开发提供了一个工具箱。
The last decade has seen remarkable advances in the development of drug delivery systems as alternative to parenteral injection-based delivery of insulin. Neonatal Fc receptor (FcRn)-mediated transcytosis has been recently proposed as a strategy to increase the transport of drugs across the intestinal epithelium. FcRn-targeted nanoparticles (NPs) could hijack the FcRn transcytotic pathway and cross the epithelial cell layer. In this study, a novel nanoparticulate system for insulin delivery based on porous silicon NPs is proposed. After surface conjugation with albumin and loading with insulin, the NPs are encapsulated into a pH-responsive polymeric particle by nanoprecipitation. The developed NP formulation shows controlled size and homogeneous size distribution. Transmission electron microscopy (TEM) images show successful encapsulation of the NPs into pH-sensitive polymeric particles. No insulin release is detected at acidic conditions, but a controlled release profile is observed at intestinal pH. Toxicity studies show high compatibility of the NPs with intestinal cells. In vitro insulin permeation across the intestinal epithelium shows approximately fivefold increase when insulin is loaded into FcRn-targeted NPs. Overall, these FcRn-targeted NPs offer a toolbox in the development of targeted therapies for oral delivery of insulin.