Xu Bin, Cao Qinying, Zhang Yang, Yu Weijiang, Zhu Jiangying, Liu Depeng, Jiang Guohua
National Engineering Laboratory for Textile Fiber Materials and Processing Technology (Zhejiang), Hangzhou, Zhejiang 310018, China.
Shijiazhuang Obstetrics and Gynecology Hospital, Shijiazhuang, Hebei 050011, China.
ACS Biomater Sci Eng. 2018 Jul 9;4(7):2473-2483. doi: 10.1021/acsbiomaterials.8b00626. Epub 2018 Jun 26.
A self-responsive insulin delivery system is highly desirable because of its high sensitivity dependent on blood glucose levels. Herein, a smart pH-triggered and glucose-mediated transdermal delivery system, insulin-loaded and ZnO quantum dots (ZnO QDs) capped mesoporous bioactive glasses (MBGs) integrated with microneedles (MNs), was developed to achieve control and painless administration. ZnO QDs as a promise pH-responsive switch were employed to cap the nanopores of MBGs via electrostatic interaction. The drug (insulin) and glucose-responsive factor (glucose oxidase/catalase, GO/CAT) were sealed into the pores of MBGs. GO/CAT in the MBGs could catalyze glucose to form gluconic acid, resulting decrease in the local pH. The ZnO QDs on the surface of the MBGs could be dissolved in the acidic condition, leading to disassembly of the pH-sensitive MBGs and then release of preloaded insulin from the MBGs. As a result of administration in a diabetic model, an excellent hypoglycemic effect and lower hypoglycemia risk were obtained. These results indicate that as-prepared pH-triggered and glucose-mediated transdermal delivery systems have hopeful applications in the treatment of diabetes.
由于其对血糖水平具有高度敏感性，一种自我响应式胰岛素递送系统是非常理想的。在此，开发了一种智能的pH触发和葡萄糖介导的经皮递送系统，即负载胰岛素且用氧化锌量子点（ZnO QDs）包覆的介孔生物活性玻璃（MBGs）与微针（MNs）集成，以实现可控且无痛给药。ZnO QDs作为一种有前景的pH响应开关，通过静电相互作用用于包覆MBGs的纳米孔。药物（胰岛素）和葡萄糖响应因子（葡萄糖氧化酶/过氧化氢酶，GO/CAT）被密封在MBGs的孔中。MBGs中的GO/CAT可催化葡萄糖形成葡萄糖酸，导致局部pH值降低。MBGs表面的ZnO QDs可在酸性条件下溶解，导致pH敏感的MBGs解体，进而使预先负载在MBGs中的胰岛素释放出来。在糖尿病模型中给药的结果显示，获得了优异的降血糖效果且低血糖风险较低。这些结果表明，所制备的pH触发和葡萄糖介导的经皮递送系统在糖尿病治疗中具有广阔的应用前景。
