Li Lei, Jiang Guohua, Yu Weijiang, Liu Depeng, Chen Hua, Liu Yongkun, Huang Qin, Tong Zaizai, Yao Juming, Kong Xiangdong
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China.
Department of Materials Engineering, Zhejiang Sci Tech University, Hangzhou 310018, China; National Engineering Laboratory for Textile Fiber Materials and Processing Technology (Zhejiang), Hangzhou 310018, China; Key Laboratory of Advanced Textile Materials and Manufacturing Technology (ATMT), Ministry of Education, Hangzhou 310018, China.
Mater Sci Eng C Mater Biol Appl. 2016 Dec 1;69:37-45. doi: 10.1016/j.msec.2016.06.059. Epub 2016 Jun 21.
Development of an oral delivery strategy for insulin therapeutics has drawn much attention in recent years. In this study, a glucose-responsive nanocarriers for loading of insulin has been prepared firstly. The resultant nanocarriers exhibited relative low cytotoxicity against Caco-2 cells and excellent stability against protein solution. The insulin release behaviors were evaluated triggered by pH and glucose in vitro. In order to enhance the oral bioavailability of insulin, the insulin-loaded glucose-responsive nanocarriers were further encapsulated into a three-dimensional (3D) hyaluronic acid (HA) hydrogel environment for overcoming multiple barriers and providing multi-protection for insulin during the transport process. The hypoglycemic effect for oral delivery of insulin was studied in vivo. After oral administration to the diabetic rats, the released insulin from hydrogel systems containing insulin-loaded glucose-responsive nanocarriers exhibited an effective hypoglycemic effect for longer time compared with insulin-loaded nanocarriers.
近年来，胰岛素治疗药物口服给药策略的研发备受关注。在本研究中，首先制备了用于负载胰岛素的葡萄糖响应性纳米载体。所得纳米载体对Caco-2细胞表现出相对较低的细胞毒性，并且对蛋白质溶液具有优异的稳定性。在体外评估了由pH值和葡萄糖触发的胰岛素释放行为。为了提高胰岛素的口服生物利用度，将负载胰岛素的葡萄糖响应性纳米载体进一步封装在三维（3D）透明质酸（HA）水凝胶环境中，以克服多种屏障并在运输过程中为胰岛素提供多重保护。对胰岛素口服给药的降血糖作用进行了体内研究。给糖尿病大鼠口服给药后，与负载胰岛素的纳米载体相比，含有负载胰岛素的葡萄糖响应性纳米载体的水凝胶系统释放的胰岛素在更长时间内表现出有效的降血糖作用。
