Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2100, Denmark.
Biomaterials. 2013 Dec;34(37):9678-87. doi: 10.1016/j.biomaterials.2013.08.048. Epub 2013 Sep 7.
Chitosan nanoparticles (NC) have excellent capacity for protein entrapment, favorable epithelial permeability, and are regarded as promising nanocarriers for oral protein delivery. Herein, we designed and evaluated a class of core shell corona nanolipoparticles (CSC) to further improve the absorption through enhanced intestinal mucus penetration. CSC contains chitosan nanoparticles as a core component and pluronic F127-lipid vesicles as a shell with hydrophilic chain and polyethylene oxide PEO as a corona. These particles were developed by hydration of a dry pluronic F127-lipid film with NC suspensions followed by extrusion. Insulin nested inside CSC was well protected from enzymatic degradation. Compared with NC, CSC exhibited significantly higher efficiency of mucosal penetration and, consequently, higher cellular internalization of insulin in mucus secreting E12 cells. The cellular level of insulin after CSC treatment was 36-fold higher compared to treatment with free insulin, and 10-fold higher compared to NC. CSC significantly facilitated the permeation of insulin across the ileum epithelia, as demonstrated in an ex vivo study and an in vivo absorption study. CSC pharmacological studies in diabetic rats showed that the hypoglycemic effects of orally administrated CSC were 2.5-fold higher compared to NC. In conclusion, CSC is a promising oral protein delivery system to enhance the stability, intestinal mucosal permeability, and oral absorption of insulin.
壳聚糖纳米粒（NC）具有优异的蛋白质包封能力、良好的上皮通透性，被认为是有前途的口服蛋白递药纳米载体。本文设计并评价了一类核壳冠状纳米脂质体（CSC），通过增强肠道黏液穿透来进一步提高吸收。CSC 以壳聚糖纳米粒为核成分，以亲水性链的泊洛沙姆 F127-脂质体为壳，以聚氧乙烯 PEO 为冠。这些粒子是通过将干燥的泊洛沙姆 F127-脂质体薄膜水化到 NC 悬浮液中，然后进行挤压而开发的。胰岛素嵌套在 CSC 中可以很好地免受酶降解。与 NC 相比，CSC 表现出更高的黏膜穿透效率，从而使 E12 黏液分泌细胞中胰岛素的细胞内化效率更高。与游离胰岛素相比，经 CSC 处理后的细胞内胰岛素水平提高了 36 倍，与 NC 相比提高了 10 倍。CSC 显著促进胰岛素穿过回肠上皮的渗透，在离体研究和体内吸收研究中均得到了证实。在糖尿病大鼠的 CSC 药理学研究中，口服 CSC 的降血糖作用比 NC 高 2.5 倍。总之，CSC 是一种有前途的口服蛋白递药系统，可提高胰岛素的稳定性、肠道黏膜通透性和口服吸收。
