Zhang Yan, Du Xuli, Zhang Yu, Li Guofei, Cai Cuifang, Xu Jinghua, Tang Xing
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, 110016, China; Normal College, Shenyang University, Shenyang, 110044, China.
Macromol Biosci. 2014 Jun;14(6):842-52. doi: 10.1002/mabi.201300515. Epub 2014 Apr 16.
This work deals with the synthesis of insulin loaded nanoparticles (NPs) composed of thiolated Eudragit L100 (Eul-cys) and reduced glutathione (GSH) as potential nanocarriers for oral delivery of insulin. Perfectly spherical NPs with an average particle size of nearly 200-300 nm are prepared. The insulin release from Eul-cys/GSH and Eul-cys NPs in PBS (pH 7.4) shows that GSH can slightly decrease the release rate of insulin. Eul-cys in combination with GSH or sodium caprate (SC) is evaluated for its permeation enhancing effect of FITC-insulin using the Caco-2 monolayer and Caco-2/HT29-MTX co-cultured cells models. SC results in greater permeation enhancement compared to GSH. However, GSH proves to be less toxic. Paracellular transport of insulin represents the main mechanism by which the NPs facilitate insulin permeation through the intestinal epithelium, whereas a number of NPs are also taken up by the cells and release insulin within the cells.
本研究致力于合成由巯基化的Eudragit L100（Eul-cys）和还原型谷胱甘肽（GSH）组成的负载胰岛素的纳米颗粒（NPs），作为胰岛素口服给药的潜在纳米载体。制备出了平均粒径接近200 - 300nm的完美球形纳米颗粒。Eul-cys/GSH和Eul-cys纳米颗粒在PBS（pH 7.4）中的胰岛素释放表明，GSH可略微降低胰岛素的释放速率。使用Caco-2单层细胞和Caco-2/HT29-MTX共培养细胞模型，评估了Eul-cys与GSH或癸酸钠（SC）联合使用对FITC-胰岛素的渗透增强作用。与GSH相比，SC导致更大的渗透增强。然而，GSH毒性较小。胰岛素的细胞旁转运是纳米颗粒促进胰岛素透过肠上皮渗透的主要机制，而一些纳米颗粒也被细胞摄取并在细胞内释放胰岛素。
